What Exactly Is Neurogenesis?

The term ‘neurogenesis’ simply means ‘the generation of new neurons.’ Neurons are cells in the nervous system that help transfer information between the brain and the rest of the body. For the most part, these neurons are generated during embryonic development and early childhood. Conventional wisdom held that as we age, the brain loses its ability to generate new neurons. But now the consensus is that the adult brain can grow functional neuronal cells even later in life.((Gage, Fred H. 2002. “Neurogenesis in the Adult Brain.” The Journal of Neuroscience 22 (3): 612-13. https://doi.org/10.1523/jneurosci.22-03-00612.2002))((Kumar A, Pareek V, Faiq MA, Ghosh SK, Kumari C. ADULT NEUROGENESIS IN HUMANS: A Review of Basic Concepts, History, Current Research, and Clinical Implications. Innov Clin Neurosci. 2019 May 1;16(5-6):30-37. PMID: 31440399; PMCID: PMC6659986))((Ming, Guo-li, and Hongjun Song. 2011. “Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions.” Neuron 70 (4): 687-702. https://doi.org/10.1016/j.neuron.2011.05.001))

The first indications of regeneration of adult brain cells came as early as the 1960s and evidence has piled up ever since to prove the concept of neurogenesis in adults.((Kumar A, Pareek V, Faiq MA, Ghosh SK, Kumari C. ADULT NEUROGENESIS IN HUMANS: A Review of Basic Concepts, History, Current Research, and Clinical Implications. Innov Clin Neurosci. 2019 May 1;16(5-6):30-37. PMID: 31440399; PMCID: PMC6659986)) Studies conducted in lab animals as well as in humans have validated this idea, and research is underway to understand how we can manipulate this process to boost brain performance.((Ming, Guo-li, and Hongjun Song. 2011. “Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions.” Neuron 70 (4): 687-702. https://doi.org/10.1016/j.neuron.2011.05.001))

Neurogenesis includes several developmental stages.((LaDage, Lara D. 2015. “Environmental Change, the Stress Response, and Neurogenesis: Fig. 1.” Integrative and Comparative Biology 55 (3): 372–83. https://doi.org/10.1093/icb/icv040)) The cells first differentiate and multiply into immature neurons. It is found that 700 new neurons are added to the human brain within a day and several of them die within 2 weeks.((Kumar A, Pareek V, Faiq MA, Ghosh SK, Kumari C. ADULT NEUROGENESIS IN HUMANS: A Review of Basic Concepts, History, Current Research, and Clinical Implications. Innov Clin Neurosci. 2019 May 1;16(5-6):30-37. PMID: 31440399; PMCID: PMC6659986))((Stangl, Doris, and Sandrine Thuret. 2009. “Impact of Diet on Adult Hippocampal Neurogenesis.” Genes & Nutrition 4 (4): 271–82. https://doi.org/10.1007/s12263-009-0134-5)) The surviving neurons then migrate into the layers where they mature and are functionally integrated into the existing neural circuits. This process usually takes up to 12 weeks.((LaDage, Lara D. 2015. “Environmental Change, the Stress Response, and Neurogenesis: Fig. 1.” Integrative and Comparative Biology 55 (3): 372–83. https://doi.org/10.1093/icb/icv040))

Why Is Neurogenesis Important?

Neurogenesis in the adult brain occurs mainly in two regions, one of which is the dentate gyrus in the hippocampus.((Kumar A, Pareek V, Faiq MA, Ghosh SK, Kumari C. ADULT NEUROGENESIS IN HUMANS: A Review of Basic Concepts, History, Current Research, and Clinical Implications. Innov Clin Neurosci. 2019 May 1;16(5-6):30-37. PMID: 31440399; PMCID: PMC6659986)) The hippocampal area plays a critical role in learning and memory, as well as in spatial navigation and mood regulation.((Dhikav, Vikas, and Kuljeet Singh Anand. 2012. “Hippocampus in Health and Disease: An Overview.” Annals of Indian Academy of Neurology 15 (4): 239. https://doi.org/10.4103/0972-2327.104323))((Anacker, Christoph, and René Hen. 2017. “Adult Hippocampal Neurogenesis and Cognitive Flexibility — Linking Memory and Mood.” Nature Reviews Neuroscience 18 (6): 335–46. https://doi.org/10.1038/nrn.2017.45)) These are basic functions we need to conduct our day-to-day activities and their impairment will severely impact our quality of life.

Age is one crucial factor that results in cognitive decline, thus lowering brain performance.((Murman, Daniel. 2015. “The Impact of Age on Cognition.” Seminars in Hearing 36 (03): 111–21. https://doi.org/10.1055/s-0035-1555115)) In addition, a host of other factors including stress, lack of sleep, and neurological disorders also impact brain health. Therefore, continued neuron generation in this area is important to maintain brain function and boost cognitive health, which in turn will help us effectively carry out the basic and complex tasks of daily life.((Ming, Guo-li, and Hongjun Song. 2011. “Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions.” Neuron 70 (4): 687–702. https://doi.org/10.1016/j.neuron.2011.05.001)) Neurogenesis is also important to maintain cognitive flexibility—meaning adapting the brain to different concepts and activities and switching attention between them.((Toda, Tomohisa, Sarah L. Parylak, Sara B. Linker, and Fred H. Gage. 2018. “The Role of Adult Hippocampal Neurogenesis in Brain Health and Disease.” Molecular Psychiatry 24 (1): 67–87. https://doi.org/10.1038/s41380-018-0036-2))

Factors Influencing Neurogenesis

Theoretically, neurons in the adult brain can be generated as and when required if conductive stimuli are provided. Every stage of the adult neurogenesis process is highly sensitive to factors such as age, stress, disease conditions, diet, and physical activity. Some of these aspects promote neurogenesis while others suppress it.((Ming, Guo-li, and Hongjun Song. 2011. “Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions.” Neuron 70 (4): 687–702. https://doi.org/10.1016/j.neuron.2011.05.001))

Chemical agents inside the brain such as corticosteroids (that negatively affect neurogenesis) and neurotrophic factors (that stimulate the process) are the mediators behind these modifications.((Kumar A, Pareek V, Faiq MA, Ghosh SK, Kumari C. ADULT NEUROGENESIS IN HUMANS: A Review of Basic Concepts, History, Current Research, and Clinical Implications. Innov Clin Neurosci. 2019 May 1;16(5-6):30-37. PMID: 31440399; PMCID: PMC6659986))

What Are BDNF and NGF and Why Are They Important?

Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play critical roles in regulating adult neurogenesis.((Miranda, Magdalena, Juan Facundo Morici, María Belén Zanoni, and Pedro Bekinschtein. 2019. “Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain.” Frontiers in Cellular Neuroscience 13 (August). https://doi.org/10.3389/fncel.2019.00363))((Allen, Shelley J., Judy J. Watson, Deborah K. Shoemark, Neil U. Barua, and Nikunj K. Patel. 2013. “GDNF, NGF and BDNF as Therapeutic Options for Neurodegeneration.” Pharmacology & Therapeutics 138 (2): 155–75. https://doi.org/10.1016/j.pharmthera.2013.01.004)) BDNF and NGF are known to regulate cell proliferation, differentiation, and survival of existing neurons.((Huang, Eric J, and Louis F Reichardt. 2001. “Neurotrophins: Roles in Neuronal Development and Function.” Annual Review of Neuroscience 24 (1): 677–736. https://doi.org/10.1146/annurev.neuro.24.1.677))

Increased BDNF and NGF levels are strongly associated with enhanced neurogenesis while a decrease in them is linked to decreased cognitive development.((Budni, Josiane, Tatiani Bellettini-Santos, Francielle Mina, Michelle Lima Garcez, and Alexandra Ioppi Zugno. 2015. “The Involvement of BDNF, NGF and GDNF in Aging and Alzheimer’s Disease.” Aging and Disease 6 (5): 331. https://doi.org/10.14336/ad.2015.0825))

Nootropics and Supplements That Influence Neurogenesis

Nootropics, aka cognitive enhancers or ‘smart drugs, are substances that influence cognitive performance, thereby enhancing mental functions such as memory, attention, and creativity.((Suliman, Noor Azuin, Che Norma Mat Taib, Mohamad Aris Mohd Moklas, Mohd Ilham Adenan, Mohamad Taufik Hidayat Baharuldin, and Rusliza Basir. 2016. “Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic.” Evidence-Based Complementary and Alternative Medicine 2016: 1–12. https://doi.org/10.1155/2016/4391375))((Srivastava, A., P. Srivastava, A. Pandey, V. K. Khanna, and A. B. Pant. 2018. Phytomedicine: A Potential Alternative Medicine in Controlling Neurological Disorders. Elsevier))These can be synthetic drugs such as Noopept and Piracetam or natural herbs such as Ginseng and Lion’s Mane Mushroom.((Srivastava, A., P. Srivastava, A. Pandey, V. K. Khanna, and A. B. Pant. 2018. Phytomedicine: A Potential Alternative Medicine in Controlling Neurological Disorders. Elsevier)) Although the concept of using nootropics to improve brain function is relatively new in western medicine, they have long been used in Ayurvedic and indigenous medicine.((Kulkarni, Reena, KJ Girish, and Abhimanyu Kumar. 2012. “Nootropic Herbs (Medhya Rasayana) in Ayurveda: An Update.” Pharmacognosy Reviews 6 (12): 147. https://doi.org/10.4103/0973-7847.99949))

These nootropic compounds act through different modes of action including increasing blood flow to the brain and modifying the levels of neurotransmitters and hormones.((Srivastava, A., P. Srivastava, A. Pandey, V. K. Khanna, and A. B. Pant. 2018. Phytomedicine: A Potential Alternative Medicine in Controlling Neurological Disorders. Elsevier)) Some have also shown the ability to improve adult neurogenesis, thus promoting neuron generation. Below is a list of such nootropic compounds that have proven benefits in brain regeneration.

1. Noopept

Noopept is a synthetic nootropic substance that is derived from the drug Piracetam. It is known for its neuroprotective, cognitive enhancing, and anxiety-reducing properties.((Ostrovskaya, Rita U, Yulia V Vakhitova, Uliyana Sh Kuzmina, Milyausha Kh Salimgareeva, Liana F Zainullina, Tatiana A Gudasheva, Vener A Vakhitov, and Sergey B Seredenin. 2014. “Neuroprotective Effect of Novel Cognitive Enhancer Noopept on AD-Related Cellular Model Involves the Attenuation of Apoptosis and Tau Hyperphosphorylation.” Journal of Biomedical Science 21 (1): 1–9. https://doi.org/10.1186/s12929-014-0074-2)) It shows a wide range of cognitive-improving abilities such as boosting memory and improving learning without a sedative effect.((Ostrovskaya, Rita U, Yulia V Vakhitova, Uliyana Sh Kuzmina, Milyausha Kh Salimgareeva, Liana F Zainullina, Tatiana A Gudasheva, Vener A Vakhitov, and Sergey B Seredenin. 2014. “Neuroprotective Effect of Novel Cognitive Enhancer Noopept on AD-Related Cellular Model Involves the Attenuation of Apoptosis and Tau Hyperphosphorylation.” Journal of Biomedical Science 21 (1): 1–9. https://doi.org/10.1186/s12929-014-0074-2)) The mode of action of Noopept comes from the antioxidant, anti-inflammatory, and anti-neurotoxic effects of the drug.((Ostrovskaia, R. U., T. A. Gudasheva, T. A. Voronina, and S. B. Seredenin. 2002. “The Original Novel Nootropic and Neuroprotective Agent Noopept.” Eksperimental’naia i klinicheskaia farmakologiia 65(5):66–72))

This nootropic triggers the expression of BDNF and NGF in the hippocampus.((Ostrovskaya, R. U., T. A. Gudasheva, A. P. Zaplina, Ju. V. Vahitova, M. H. Salimgareeva, R. S. Jamidanov, and S. B. Seredenin. 2008. “Noopept Stimulates the Expression of NGF and BDNF in Rat Hippocampus.” Bulletin of Experimental Biology and Medicine 146 (3): 334–37. https://doi.org/10.1007/s10517-008-0297-x)) Since elevated BDNF and NGF levels are associated with increased neurogenesis, we can assume that Noopept might also influence neurogenesis.

2. Piracetam

Piracetam is another synthetic nootropic drug that is structurally related to Noopept. It is known to improve memory and concentration.((Taupin, Philippe. 2009. “Nootropic Agents Stimulate Neurogenesis.” Expert Opinion on Therapeutic Patents 19 (5): 727–30. https://doi.org/10.1517/13543770902721303)) It also has neuroprotective properties and boosts neuroplasticity.((Winblad, Bengt. 2006. “Piracetam: A Review of Pharmacological Properties and Clinical Uses.” CNS Drug Reviews 11 (2): 169–82. https://doi.org/10.1111/j.1527-3458.2005.tb00268.x))

This nootropic has been found to stimulate the differentiation of human neural stem cells.((Taupin, Philippe. 2009. “Nootropic Agents Stimulate Neurogenesis.” Expert Opinion on Therapeutic Patents 19 (5): 727–30. https://doi.org/10.1517/13543770902721303))Researchers predict that this drug can be used to promote adult neurogenesis.

3. Choline Sources (CDP-Choline, Alpha GPC, Centrophenoxine)

Choline is an essential nutrient that is important in cell composition and metabolic pathways, especially in the brain.((Kim, Jong Whi, Kyu Ri Hahn, Dae Young Yoo, Hyo Young Jung, In Koo Hwang, Je Kyung Seong, and Yeo Sung Yoon. 2019. “Methionine-Choline Deprivation Impairs Adult Hippocampal Neurogenesis in C57BL/6 Mice.” Journal of Medicinal Food 22 (4): 344–54. https://doi.org/10.1089/jmf.2018.4247)) Choline is also known to regulate neuronal plasticity.((Goh, EyleenL.K., and EuniceW. M. Chin. 2019. “Modulating Neuronal Plasticity with Choline.” Neural Regeneration Research 14 (10): 1697. https://doi.org/10.4103/1673-5374.257516)) Because humans can’t synthesize it in adequate amounts, consuming choline through diet and supplements is critical.((Derbyshire, Emma, and Rima Obeid. 2020. “Choline, Neurological Development and Brain Function: A Systematic Review Focusing on the First 1000 Days.” Nutrients 12 (6): 1731. https://doi.org/10.3390/nu12061731)) This has been widely used as a nootropic drug due to its neuro-enhancing properties.

Research found that a diet containing insufficient choline amounts severely reduced hippocampal neurogenesis.((Kim, Jong Whi, Kyu Ri Hahn, Dae Young Yoo, Hyo Young Jung, In Koo Hwang, Je Kyung Seong, and Yeo Sung Yoon. 2019. “Methionine-Choline Deprivation Impairs Adult Hippocampal Neurogenesis in C57BL/6 Mice.” Journal of Medicinal Food 22 (4): 344–54. https://doi.org/10.1089/jmf.2018.4247)) Supplementation of choline during the age of development has been shown to increase hippocampal neurogenesis in adulthood.((Glenn, Melissa J., Raven S. Adams, and Lauren McClurg. 2012. “Supplemental Dietary Choline during Development Exerts Antidepressant-like Effects in Adult Female Rats.” Brain Research 1443 (March): 52–63. https://doi.org/10.1016/j.brainres.2012.01.018)) Increased intake of choline during the early years is also known to boost memory and slow down age-related memory decline later in life.((Glenn, Melissa J., Erin M. Gibson, Elizabeth D. Kirby, Tiffany J. Mellott, Jan K. Blusztajn, and Christina L. Williams. 2007. “Prenatal Choline Availability Modulates Hippocampal Neurogenesis and Neurogenic Responses to Enriching Experiences in Adult Female Rats.” European Journal of Neuroscience 25 (8): 2473–82. https://doi.org/10.1111/j.1460-9568.2007.05505.x))

One study reported that the intake of choline supplements by pregnant female rats has an effect on hippocampal neurogenesis in the offspring.((Glenn, Melissa J., Erin M. Gibson, Elizabeth D. Kirby, Tiffany J. Mellott, Jan K. Blusztajn, and Christina L. Williams. 2007. “Prenatal Choline Availability Modulates Hippocampal Neurogenesis and Neurogenic Responses to Enriching Experiences in Adult Female Rats.” European Journal of Neuroscience 25 (8): 2473–82. https://doi.org/10.1111/j.1460-9568.2007.05505.x)) Choline has also been shown to increase BDNF levels in laboratory cell culture studies.((Johansson, Jan, Elena Formaggio, Guido Fumagalli, and Christian Chiamulera. 2009. “Choline Up-Regulates BDNF and Down-Regulates TrkB Neurotrophin Receptor in Rat Cortical Cell Culture.” NeuroReport 20 (9): 828–32. https://doi.org/10.1097/wnr.0b013e32832b7324))

4. Ashwagandha

Ashwagandha (scientific name Withania somnifera), also known as ‘Indian winter cherry’, has been used in Ayurvedic and indigenous medicinal practices for its beneficial properties including antioxidant, anti-inflammatory, as well as anti-cancer properties.((Shah, ZahoorA, and Aparna Raghavan. 2015. “Withania Somnifera: A Pre-Clinical Study on Neuroregenerative Therapy for Stroke.” Neural Regeneration Research 10 (2): 183. https://doi.org/10.4103/1673-5374.152362)) It is a natural nootropic known for its neuro-regenerative properties.((Shah, ZahoorA, and Aparna Raghavan. 2015. “Withania Somnifera: A Pre-Clinical Study on Neuroregenerative Therapy for Stroke.” Neural Regeneration Research 10 (2): 183. https://doi.org/10.4103/1673-5374.152362)) In traditional medicine, Ashwagandha is considered a powerful adaptogen due to its ability to improve the body’s stress response.((Singh, N, M Bhalla, P De Jager, and M Gilca. 2011. “An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda.” African Journal of Traditional, Complementary and Alternative Medicines 8 (5S). https://doi.org/10.4314/ajtcam.v8i5s.9))

In one study, Ashwagandha leaf powder was proven to restore BDNF levels and boost memory in rats with experimentally-induced cognitive dysfunction.((Manchanda, Shaffi, and Gurcharan Kaur. 2017. “Withania Somnifera Leaf Alleviates Cognitive Dysfunction by Enhancing Hippocampal Plasticity in High Fat Diet Induced Obesity Model.” BMC Complementary and Alternative Medicine 17 (1): 1–13. https://doi.org/10.1186/s12906-017-1652-0)) In a similar study, Ashwagandha leaf extract was shown to reverse the effects of chemically-induced neurodegenerative conditions.((Konar, Arpita, Navjot Shah, Rumani Singh, Nishant Saxena, Sunil C. Kaul, Renu Wadhwa, and Mahendra K. Thakur. 2011. “Protective Role of Ashwagandha Leaf Extract and Its Component Withanone on Scopolamine-Induced Changes in the Brain and Brain-Derived Cells.” PloS One 6 (11): e27265. https://doi.org/10.1371/journal.pone.0027265))

5. Lion’s Mane Mushroom (Hericium erinaceus)

Lion’s mane mushroom, a renowned nootropic, is a type of edible mushroom that is named after its appearance, which resembles a Lion’s mane. It’s known for its exceptional medicinal properties and it produces several bioactive compounds including ß-glucans, alkaloids, sterols, and volatile aromatic compounds.((Roda, Elisa, Erica Cecilia Priori, Daniela Ratto, Fabrizio De Luca, Carmine Di Iorio, Paola Angelone, Carlo Alessandro Locatelli, et al. 2021. “Neuroprotective Metabolites of Hericium Erinaceus Promote Neuro-Healthy Aging.” International Journal of Molecular Sciences 22 (12): 6379. https://doi.org/10.3390/ijms22126379))

Among its many benefits, Lion’s mane mushroom also possesses brain regenerative properties.((Ratto, Daniela, Federica Corana, Barbara Mannucci, Erica Cecilia Priori, Filippo Cobelli, Elisa Roda, Beatrice Ferrari, et al. 2019. “Hericium Erinaceus Improves Recognition Memory and Induces Hippocampal and Cerebellar Neurogenesis in Frail Mice during Aging.” Nutrients 11 (4): 715. https://doi.org/10.3390/nu11040715)) It has been shown that certain chemical compounds in Lion’s mane mushroom stimulate NGF and BDNF synthesis in laboratory models.((Ratto, Daniela, Federica Corana, Barbara Mannucci, Erica Cecilia Priori, Filippo Cobelli, Elisa Roda, Beatrice Ferrari, et al. 2019. “Hericium Erinaceus Improves Recognition Memory and Induces Hippocampal and Cerebellar Neurogenesis in Frail Mice during Aging.” Nutrients 11 (4): 715. https://doi.org/10.3390/nu11040715))

6. Ginseng (Panax ginseng)

Ginseng is a medicinal herb widely known for its immune-modulating, anti-inflammatory, and antioxidant properties. This nootropic is also used for treating and preventing neurodegenerative diseases and for enhancing cognitive functions.((Hou, Wei, Yingping Wang, Peihe Zheng, and Ranji Cui. 2020. “Effects of Ginseng on Neurological Disorders.” Frontiers in Cellular Neuroscience 14 (March). https://doi.org/10.3389/fncel.2020.00055))

Ginsenoside Rg1, a major bioactive compound found in ginseng is responsible for several important characteristics including stimulating neurogenesis and expressing neurotrophic factors such as BDNF.((Jiang, Bo, Zhe Xiong, Jun Yang, Wei Wang, Yue Wang, Zhuang-Li Hu, Fang Wang, and Jian-Guo Chen. 2012. “Antidepressant-like Effects of Ginsenoside Rg1 Are due to Activation of the BDNF Signalling Pathway and Neurogenesis in the Hippocampus.” British Journal of Pharmacology 166 (6): 1872–87. https://doi.org/10.1111/j.1476-5381.2012.01902.x)) Ginseng (particularly red ginseng) has also been reported to lower the neuron cell damage triggered by oxidative stress.((Iqbal, H., S. K. Kim, K. M. Cha, M. S. Jeong, P. Ghosh, and D. Kwon Rhee, “Korean Red Ginseng Alleviates Neuroinflammation and Promotes Cell Survival in the Intermittent Heat Stress-Induced Rat Brain by Suppressing Oxidative Stress via Estrogen Receptor Beta and Brain-Derived Neurotrophic Factor Upregulation.” 2020. Journal of Ginseng Research 44 (4): 593–602. https://doi.org/10.1016/j.jgr.2019.05.007))

7. L-Theanine

L-theanine, a potent nootropic amino acid found in green tea and some mushrooms, is known for its benefits on brain health such as neuroprotective, cognitive boosting, and anti-stress properties.((Nathan, Pradeep, Kristy Lu, M. Gray, and C. Oliver. 2006. “The Neuropharmacology of L-Theanine(N-Ethyl-L-Glutamine).” Journal of Herbal Pharmacotherapy 6 (2): 21–30. https://doi.org/10.1300/j157v06n02_02))((Wang, Qi, Yafeng Zheng, Chi-Tang Ho, Juqing Huang, Xuefang Guan, Chenchun Lai, Huiying Gao, and Bin Lin. 2021. “L-Theanine as a Promising Agent on Brain Health-Promoting Foods – A Review.” Journal of Food Bioactives 13: 32–39. https://doi.org/10.31665/jfb.2020.13257))

L-theanine has demonstrated its ability to improve attention and enhance memory, thus improving executive function.((Baba, Yoshitake, Shun Inagaki, Sae Nakagawa, Toshiyuki Kaneko, Makoto Kobayashi, and Takanobu Takihara. 2021. “Effects of L-Theanine on Cognitive Function in Middle-Aged and Older Subjects: A Randomized Placebo-Controlled Study.” Journal of Medicinal Food 24 (4): 333–41. https://doi.org/10.1089/jmf.2020.4803))

One study found that treatment with L-theanine for a period of 3 weeks significantly increased BDNF levels in the hippocampus of mice.((Wakabayashi, Chisato, Tadahiro Numakawa, Midori Ninomiya, Shuichi Chiba, and Hiroshi Kunugi. 2011. “Behavioral and Molecular Evidence for Psychotropic Effects in L-Theanine.” Psychopharmacology 219 (4): 1099–1109. https://doi.org/10.1007/s00213-011-2440-z)) Another study reported that L-theanine rectified reduced BDNF levels, thus reversing neurotoxicity.((Cho, Hong-Suk, Seung Kim, Sook-Young Lee, Jeong Ae Park, Sung-Jun Kim, and Hong Sung Chun. 2008. “Protective Effect of the Green Tea Component, L-Theanine on Environmental Toxins-Induced Neuronal Cell Death.” NeuroToxicology 29 (4): 656–62. https://doi.org/10.1016/j.neuro.2008.03.004)) L-theanine is also known to promote neurogenesis, thus improving cognitive impairment.((Baba, Yoshitake, Shun Inagaki, Sae Nakagawa, Toshiyuki Kaneko, Makoto Kobayashi, and Takanobu Takihara. 2021. “Effects of L-Theanine on Cognitive Function in Middle-Aged and Older Subjects: A Randomized Placebo-Controlled Study.” Journal of Medicinal Food 24 (4): 333–41. https://doi.org/10.1089/jmf.2020.4803))

8. Bacopa Monnieri

Bacopa monnieri, a natural nootropic, is a medicinal plant that is used in Ayurvedic medicine for the treatment of various conditions such as memory problems, cognitive decline, and anxiety.((Kwon, Hyun Jung, Hyo Young Jung, Kyu Ri Hahn, Woosuk Kim, Jong Whi Kim, Dae Young Yoo, Yeo Sung Yoon, In Koo Hwang, and Dae Won Kim. 2018. “Bacopa Monnieri Extract Improves Novel Object Recognition, Cell Proliferation, Neuroblast Differentiation, Brain-Derived Neurotrophic Factor, and Phosphorylation of CAMP Response Element-Binding Protein in the Dentate Gyrus.” Laboratory Animal Research 34 (4): 239. https://doi.org/10.5625/lar.2018.34.4.239))((Suliman, Noor Azuin, Che Norma Mat Taib, Mohamad Aris Mohd Moklas, Mohd Ilham Adenan, Mohamad Taufik Hidayat Baharuldin, and Rusliza Basir. 2016. “Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic.” Evidence-Based Complementary and Alternative Medicine 2016: 1–12. https://doi.org/10.1155/2016/4391375))The main active compounds of the plant extracts are Bacosides, which are responsible for the memory-enhancing action.((Suliman, Noor Azuin, Che Norma Mat Taib, Mohamad Aris Mohd Moklas, Mohd Ilham Adenan, Mohamad Taufik Hidayat Baharuldin, and Rusliza Basir. 2016. “Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic.” Evidence-Based Complementary and Alternative Medicine 2016: 1–12. https://doi.org/10.1155/2016/4391375))

Several studies have found that consuming B. monnieri extract significantly raised BDNF levels in the hippocampus, thereby increasing hippocampal neurogenesis.((Kwon, Hyun Jung, Hyo Young Jung, Kyu Ri Hahn, Woosuk Kim, Jong Whi Kim, Dae Young Yoo, Yeo Sung Yoon, In Koo Hwang, and Dae Won Kim. 2018. “Bacopa Monnieri Extract Improves Novel Object Recognition, Cell Proliferation, Neuroblast Differentiation, Brain-Derived Neurotrophic Factor, and Phosphorylation of CAMP Response Element-Binding Protein in the Dentate Gyrus.” Laboratory Animal Research 34 (4): 239. https://doi.org/10.5625/lar.2018.34.4.239))((Kumar, Sourav, and Amal Chandra Mondal. 2016. “Neuroprotective, Neurotrophic and Anti-Oxidative Role of Bacopa Monnieri on CUS Induced Model of Depression in Rat.” Neurochemical Research 41 (11): 3083–94. https://doi.org/10.1007/s11064-016-2029-3))

9. Rhodiola Rosea

This therapeutic plant is a known adaptogen (a substance that helps the body fight against stress).((Khanum, Farhath, Amarinder Singh Bawa, and Brahm Singh. 2005. “Rhodiola Rosea: A Versatile Adaptogen.” Comprehensive Reviews in Food Science and Food Safety 4 (3): 55–62. https://doi.org/10.1111/j.1541-4337.2005.tb00073.x)) Rhodiola rosea is a natural nootropic that is recognized for its learning and memory enhancement properties.((Suliman, Noor Azuin, Che Norma Mat Taib, Mohamad Aris Mohd Moklas, Mohd Ilham Adenan, Mohamad Taufik Hidayat Baharuldin, and Rusliza Basir. 2016. “Establishing Natural Nootropics: Recent Molecular Enhancement Influenced by Natural Nootropic.” Evidence-Based Complementary and Alternative Medicine 2016: 1–12. https://doi.org/10.1155/2016/4391375))

Low doses of Rhodiola rosea extract have been found to stimulate cell proliferation in the hippocampus of depressed rats.((Chen, Q.G., Y.S. Zeng, Z.Q. Qu, J.Y. Tang, Y.J. Qin, P. Chung, R. Wong, and U. Hägg. 2009. “The Effects of Rhodiola Rosea Extract on 5-HT Level, Cell Proliferation and Quantity of Neurons at Cerebral Hippocampus of Depressive Rats.” Phytomedicine 16 (9): 830–38. https://doi.org/10.1016/j.phymed.2009.03.011)) Salidroside, a key component of R. rosea extracts, is a neuroprotective agent and has been shown to increase the expression of neurotrophins, including BDNF and NGF.((Zhao, Hong‐Bin, Hui Ma, Xiao‐Qin Ha, Ping Zheng, Xiao‐Yun Li, Ming Zhang, Ju‐Zi Dong, and Yin‐Shu Yang. 2014. “Salidroside Induces Rat Mesenchymal Stem Cells to Differentiate into Dopaminergic Neurons.” Cell Biology International 38 (4): 462–71. https://doi.org/10.1002/cbin.10217))((Zhu, Lingpeng, Tingting Wei, Jing Gao, Xiayun Chang, He He, Mingxing Miao, and Tianhua Yan. 2015. “Salidroside Attenuates Lipopolysaccharide (LPS) Induced Serum Cytokines and Depressive-like Behavior in Mice.” Neuroscience Letters 606 (October): 1–6. https://doi.org/10.1016/j.neulet.2015.08.025))

10. Sabroxy

Sabroxy is a commercial nootropic preparation that contains extracts from the Indian trumpet tree (Oroxylum indicum).((“Introduction – Sabroxy®.” 2020. Sabroxy®. September 9, 2020. https://sabroxy.com/sabroxy/introduction/)) It mainly contains Oroxylin A (10% minimum).((“Introduction – Sabroxy®.” 2020. Sabroxy®. September 9, 2020. https://sabroxy.com/sabroxy/introduction/)) which has been proven to induce neuron regeneration in the hippocampus.((Lee, Seungjoo, Dong Hyun Kim, Dong Hwa Lee, Su Jin Jeon, Chang Hwan Lee, Kun Ho Son, Ji Wook Jung, Chan Young Shin, and Jong Hoon Ryu. 2010. “Oroxylin A, a Flavonoid, Stimulates Adult Neurogenesis in the Hippocampal Dentate Gyrus Region of Mice.” Neurochemical Research 35 (11): 1725–32. https://doi.org/10.1007/s11064-010-0235-y)) Oroxylin A has also been shown to activate BDNF production pathways, thus regulating BDNF production.((Jeon, Se Jin, So Young Rhee, Jung Eun Seo, Hae Rang Bak, Sung Hoon Lee, Jong Hoon Ryu, Jae Hoon Cheong, et al. 2011. “Oroxylin a Increases BDNF Production by Activation of MAPK–CREB Pathway in Rat Primary Cortical Neuronal Culture.” Neuroscience Research 69 (3): 214–22. https://doi.org/10.1016/j.neures.2010.11.008))

11. Pterostilbene

Pterostilbene is an organic compound found in plants such as blueberries and grapes, as well as in resins such as Dragon’s blood.((Poulose, Shibu M., Nopporn Thangthaeng, Marshall G. Miller, and Barbara Shukitt-Hale. 2015. “Effects of Pterostilbene and Resveratrol on Brain and Behavior.” Neurochemistry International 89 (October): 227–33. https://doi.org/10.1016/j.neuint.2015.07.017))((Yang, Liang, Yuanyuan Ran, Zhenzhen Quan, Ran Wang, Qinghu Yang, Qiutian Jia, Heao Zhang, et al. 2019. “Pterostilbene, an Active Component of the Dragon’s Blood Extract, Acts as an Antidepressant in Adult Rats.” Psychopharmacology 236 (4): 1323–33. https://doi.org/10.1007/s00213-018-5138-7)) It has been proposed as a remedy for a host of conditions including heart disease and cancer.((Poulose, Shibu M., Nopporn Thangthaeng, Marshall G. Miller, and Barbara Shukitt-Hale. 2015. “Effects of Pterostilbene and Resveratrol on Brain and Behavior.” Neurochemistry International 89 (October): 227–33. https://doi.org/10.1016/j.neuint.2015.07.017))

Recently, the beneficial effects of pterostilbene in improving brain health have come to light. This compound has been found to be effective in treating neurodegenerative diseases and brain damage.((Poulose, Shibu M., Nopporn Thangthaeng, Marshall G. Miller, and Barbara Shukitt-Hale. 2015. “Effects of Pterostilbene and Resveratrol on Brain and Behavior.” Neurochemistry International 89 (October): 227–33. https://doi.org/10.1016/j.neuint.2015.07.017))((Estrela, José M., Angel Ortega, Salvador Mena, Maria L. Rodriguez, and Miguel Asensi. 2013. “Pterostilbene: Biomedical Applications.” Critical Reviews in Clinical Laboratory Sciences 50 (3): 65–78. https://doi.org/10.3109/10408363.2013.805182)) It can also enhance memory and improve age-related cognitive decline.((La Spina, M., G. Sansevero, L. Biasutto, M. Zoratti, R. Peruzzo, N. Berardi, A. Sale, and M. Azzolini., “Pterostilbene Improves Cognitive Performance in Aged Rats: An in Vivo Study.” 2019. Cellular Physiology and Biochemistry 52 (2): 232–39. https://doi.org/10.33594/000000017))

In a study using adult rats, a pterostilbene-added diet stimulated neuron generation, while increasing neurogenesis-related factors such as BDNF.((Yang, Liang, Yuanyuan Ran, Zhenzhen Quan, Ran Wang, Qinghu Yang, Qiutian Jia, Heao Zhang, et al. 2019. “Pterostilbene, an Active Component of the Dragon’s Blood Extract, Acts as an Antidepressant in Adult Rats.” Psychopharmacology 236 (4): 1323–33. https://doi.org/10.1007/s00213-018-5138-7))

Diet As a Modulator of Neurogenesis

A mounting stack of research implies that diet can considerably influence adult neurogenesis in different ways. The amount of calorie intake, frequency of meals, nutritional content, and even food texture can affect the growth and survival of new neurons.((Stangl, Doris, and Sandrine Thuret. 2009. “Impact of Diet on Adult Hippocampal Neurogenesis.” Genes & Nutrition 4 (4): 271–82. https://doi.org/10.1007/s12263-009-0134-5))

For instance, cutting down calorie intake by 30–40% has been shown to increase BDNF levels and thus, in turn, increase the adult hippocampal neurogenesis.((Lee, Jaewon, Wenzhen Duan, Jeffrey M. Long, Donald K. Ingram, and Mark P. Mattson. 2000. “Dietary Restriction Increases the Number of Newly Generated Neural Cells, and Induces BDNF Expression, in the Dentate Gyrus of Rats.” Journal of Molecular Neuroscience 15 (2): 99–108. https://doi.org/10.1385/jmn:15:2:99)) In another study, calorie restriction also improved cognitive decline by boosting BDNF levels.((Kishi, Takuya, Yoshitaka Hirooka, Tomomi Nagayama, Kengo Isegawa, Masato Katsuki, Ko Takesue, and Kenji Sunagawa. 2015. “Calorie Restriction Improves Cognitive Decline via Up-Regulation of Brain-Derived Neurotrophic Factor.” International Heart Journal 56 (1): 110–15. https://doi.org/10.1536/ihj.14-168)) On the other hand, high-calorie diets reduce BDNF levels as well as cell proliferation rates.((Stangl, Doris, and Sandrine Thuret. 2009. “Impact of Diet on Adult Hippocampal Neurogenesis.” Genes & Nutrition 4 (4): 271–82. https://doi.org/10.1007/s12263-009-0134-5))

Another study found that eating a soft diet decreases the proliferation rates of neuronal cells when compared to a solid diet.((Yamamoto, Tetsu, Akihiko Hirayama, Nobuo Hosoe, Masaru Furube, and Shusuke Hirano. 2009. “Soft-Diet Feeding Inhibits Adult Neurogenesis in Hippocampus of Mice.” The Bulletin of Tokyo Dental College 50 (3): 117–24. https://doi.org/10.2209/tdcpublication.50.117)) Researchers speculated that the action of chewing stimulated nerve cell growth.

The most important aspect of the diet that affects neurogenesis is meal content. Certain dietary components have been found to enhance the process while some others restrict. Flavonoids found in foods such as berry fruits, cocoa, and citrus fruits have been shown to increase neurogenesis in rats, and this effect was found to be mediated by BDNF.((Cichon, Natalia, Joanna Saluk-Bijak, Leslaw Gorniak, Lukasz Przyslo, and Michal Bijak. 2020. “Flavonoids as a Natural Enhancer of Neuroplasticity—an Overview of the Mechanism of Neurorestorative Action.” Antioxidants 9 (11): 1035. https://doi.org/10.3390/antiox9111035))

Vitamins including Vitamin B9, Vitamin D, and vitamin E are also known to increase adult neurogenesis.((Qiu, Wansu, Aarthi R. Gobinath, Yanhua Wen, Jehannine Austin, and Liisa A. M. Galea. 2019. “Folic Acid, but Not Folate, Regulates Different Stages of Neurogenesis in the Ventral Hippocampus of Adult Female Rats.” Journal of Neuroendocrinology 31 (10). https://doi.org/10.1111/jne.12787))((Morello, Maria, Véréna Landel, Emmanuelle Lacassagne, Kevin Baranger, Cedric Annweiler, François Féron, and Pascal Millet. 2018. “Vitamin D Improves Neurogenesis and Cognition in a Mouse Model of Alzheimer’s Disease.” Molecular Neurobiology 55 (8): 6463–79. https://doi.org/10.1007/s12035-017-0839-1))((Ciaroni, S., R. Cuppini, T. Cecchini, P. Ferri, P. Ambrogini, C. Cuppini, and P. Del Grande. 1999. “Neurogenesis in the Adult Rat Dentate Gyrus Is Enhanced by Vitamin E Deficiency.” The Journal of Comparative Neurology 411 (3): 495–502)) On the other hand, diets high in fat and refined sugars have been shown to result in low BDNF levels and impaired neurogenesis.((Molteni, R, R.J Barnard, Z Ying, C.K Roberts, and F Gómez-Pinilla. 2002. “A High-Fat, Refined Sugar Diet Reduces Hippocampal Brain-Derived Neurotrophic Factor, Neuronal Plasticity, and Learning.” Neuroscience 112 (4): 803–14. https://doi.org/10.1016/s0306-4522(02)00123-9))((Lindqvist, A., P. Mohapel, B. Bouter, H. Frielingsdorf, D. Pizzo, P. Brundin, and C. Erlanson-Albertsson. 2006. “High-Fat Diet Impairs Hippocampal Neurogenesis in Male Rats.” European Journal of Neurology 13 (12): 1385–88. https://doi.org/10.1111/j.1468-1331.2006.01500.x))

Meal frequency is another factor of diet that affects the new cell generation in the brain. Neurogenesis in the adult hippocampus can be increased by extending the time between meals. Intermittent fasting, a method that cuts down energy intake by reducing meal frequency, has been shown to increase neurogenesis and BDNF levels.((Mattson, Mark P., Wenzhen Duan, and Zhihong Guo. 2003. “Meal Size and Frequency Affect Neuronal Plasticity and Vulnerability to Disease: Cellular and Molecular Mechanisms.” Journal of Neurochemistry 84 (3): 417–31. https://doi.org/10.1046/j.1471-4159.2003.01586.x))((Baik, Sang-Ha, Vismitha Rajeev, David Yang-Wei Fann, Dong-Gyu Jo, and Thiruma V. Arumugam. 2020. “Intermittent Fasting Increases Adult Hippocampal Neurogenesis.” Brain and Behavior 10 (1): e01444. https://doi.org/10.1002/brb3.1444))

Your Lifestyle and Brain Health

A healthy lifestyle is vital to keeping your brain in good shape. Research suggests that habits such as regular exercise, better sleep schedules, and continued learning can boost the generation and survival of neurons.

Exercise

Undoubtedly, exercise is crucial to your health and wellness. Apart from its conventional benefits such as reducing the risk of heart diseases and maintaining a healthy weight, exercise has been found critical to your brain health as well. In several studies, scientists found that exercise increases BDNF levels and NGF levels in the brain, thus boosting neuron generation.((Chae, C.-H., H.-C. Lee, S.-L. Jung, T.-W. Kim, J.-H. Kim, N.-J. Kim, and H.-T. Kim. 2012. “RETRACTED: Swimming Exercise Increases the Level of Nerve Growth Factor and Stimulates Neurogenesis in Adult Rat Hippocampus.” Neuroscience 212 (June): 30–37. https://doi.org/10.1016/j.neuroscience.2012.03.030))((Liu, Patrick Z., and Robin Nusslock. 2018. “Exercise-Mediated Neurogenesis in the Hippocampus via BDNF.” Frontiers in Neuroscience 12 (February). https://doi.org/10.3389/fnins.2018.00052))((Sachdeva, Ankur. 2015. “Non Pharmacological Cognitive Enhancers – Current Perspectives.” Journal of Clinical and Diagnostic Research. https://doi.org/10.7860/jcdr/2015/13392.6186))

Sleep

Sleep is considered an essential component of a healthy lifestyle. Sound sleep enhances the functioning of the brain and cognition. According to science, many cognitive functions such as learning, memory, attention, and mood are affected by sleep disturbances.((Sachdeva, Ankur. 2015. “Non Pharmacological Cognitive Enhancers – Current Perspectives.” Journal of Clinical and Diagnostic Research. https://doi.org/10.7860/jcdr/2015/13392.6186)) In relation to this, long-term sleep deprivation was shown to result in significant decreases in hippocampal neurogenesis.((Mirescu, C., J. D. Peters, L. Noiman, and E. Gould. 2006. “Sleep Deprivation Inhibits Adult Neurogenesis in the Hippocampus by Elevating Glucocorticoids.” Proceedings of the National Academy of Sciences 103 (50): 19170–75. https://doi.org/10.1073/pnas.0608644103))

Learning

Challenging the brain with new skills stimulates the brain, increasing the new neuron survival in the hippocampus.((Gould, Elizabeth, Anna Beylin, Patima Tanapat, Alison Reeves, and Tracey J. Shors. 1999. “Learning Enhances Adult Neurogenesis in the Hippocampal Formation.” Nature Neuroscience 2 (3): 260–65. https://doi.org/10.1038/6365)) One study found that subjecting mice to running, followed by a learning-inducive environment increased neurogenesis by 30% more than either running or learning alone.((Fabel, Klaus. 2009. “Additive Effects of Physical Exercise and Environmental Enrichment on Adult Hippocampal Neurogenesis in Mice.” Frontiers in Neuroscience 3:2. https://doi.org/10.3389/neuro.22.002.2009))

Reducing Stress

Reducing stress through better lifestyle practices is another way you can improve brain regeneration. Stress rapidly and substantially reduces cell proliferation in the hippocampus, thus inhibiting neurogenesis.((Mirescu, Christian, and Elizabeth Gould. 2006. “Stress and Adult Neurogenesis.” Hippocampus 16 (3): 233–38. https://doi.org/10.1002/hipo.20155))

Final Thoughts

Maintaining a sharp and active brain is fundamental to living a productive life. Brain performance rapidly decreases as we age and therefore, taking precautions to slow down cognitive decline is crucial. Nootropics, a wholesome diet, and a healthy lifestyle can easily improve brain health, keeping neurological disorders at bay.