Editing Adult neurogenesis (section)

==Factors affecting==

===Changes in old age===
Neurogenesis is substantially reduced in the hippocampus of aged animals, raising the possibility that it may be linked to age-related declines in hippocampal function. For example, the rate of neurogenesis in aged animals is predictive of memory.<ref>{{cite journal|author=Drapeau, E.|author2=Mayo, W.|author3=Aurousseau, C.|author4=Moal, M.L.|author5=Piazza, P.|author6=Abrous, D.N.|title=Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis|journal=PNAS|date=2003|volume=100|issue=24|doi=10.1073/pnas.2334169100 |pages=14385–90|pmid=14614143|pmc=283601|bibcode=2003PNAS..10014385D|doi-access=free}}</ref> However, new born cells in aged animals are functionally integrated.<ref>{{cite journal|author=Marrone, D.F.|author2=Ramirez-Amaya, V.|author3=Barnes, C.A.|title=Neurons generated in senescence maintain capacity for functional integration|journal=Hippocampus|date=2012|volume=22|pages=1134–42|doi=10.1002/hipo.20959|pmid=21695743|issue=5|pmc=3367380}}</ref> Given that neurogenesis occurs throughout life, it might be expected that the hippocampus would steadily increase in size during adulthood, and that therefore the number of granule cells would be increased in aged animals. However, this is not the case, indicating that proliferation is balanced by cell death. Thus, it is not the addition of new neurons into the hippocampus that seems to be linked to hippocampal functions, but rather the rate of turnover of granule cells.<ref>{{cite journal |author=von Bohlen und Halbach O |title=Involvement of BDNF in age-dependent alterations in the hippocampus |journal=Front Aging Neurosci |volume=2 |year=2010 |pmid=20941325 |pmc=2952461 |doi=10.3389/fnagi.2010.00036|doi-access=free }}</ref>

===Effects of exercise===
{{main|Neurobiological effects of physical exercise#Neuroplasticity}}
Scientists have shown that physical activity in the form of voluntary exercise results in an increase in the number of newborn neurons in the hippocampus of mice and rats.<ref name=Praag99>{{cite journal |vauthors=Praag H, Christie BR, Sejnowski TJ, Gage FH | year = 1999 | title = Running enhances neurogenesis, learning, and long-term potentiation in mice | journal = Proc Natl Acad Sci U S A | volume = 96 | issue = 23| pages = 13427–31 | pmid = 10557337 | doi=10.1073/pnas.96.23.13427 | pmc=23964| bibcode=1999PNAS...9613427V | doi-access = free }}</ref><ref name="ReferenceA"/>  These and other studies have shown that learning in both species can be enhanced by physical exercise.<ref name=Praag99/> Recent research has shown that [[brain-derived neurotrophic factor]] and [[insulin-like growth factor 1]] are key mediators of exercise-induced neurogenesis.<ref name="ReferenceA">{{cite journal |vauthors=Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR | year = 2004 | title = Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo | journal = Neuroscience | volume = 124 | issue = 1| pages = 71–9 | doi = 10.1016/j.neuroscience.2003.09.029 | pmid = 14960340 | s2cid = 2718669 }}</ref><ref name="Trejo et al, 2001">{{cite journal | pmid = 11466439| pmc = 6762673| year = 2001| last1 = Carro| first1 = E| title = Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy| journal = The Journal of Neuroscience| volume = 21| issue = 15| pages = 5678–84| last2 = Trejo| first2 = J. L.| last3 = Busiguina| first3 = S| last4 = Torres-Aleman| first4 = I| doi = 10.1523/JNEUROSCI.21-15-05678.2001}}</ref> Exercise increases the production of BDNF, as well as the NR2B subunit of the NMDA receptor.<ref name="ReferenceA"/> Exercise increases the uptake of IGF-1 from the bloodstream into various brain regions, including the hippocampus. In addition, IGF-1 alters c-fos expression in the hippocampus. When IGF-1 is blocked, exercise no longer induces neurogenesis.<ref name="Trejo et al, 2001" /> Other research demonstrated that exercising mice that did not produce beta-endorphin, a mood-elevating hormone, had no change in neurogenesis. Yet, mice that did produce this hormone, along with exercise, exhibited an increase in newborn cells and their rate of survival.<ref>{{ cite web | title = Adult neurogenesis | work = Brain Briefings | publisher = [[Society for Neuroscience]] | date = June 2007 | url = http://www.sfn.org/index.aspx?pagename=brainbriefings_adult_neurogenesis | access-date = 2011-11-26 }}</ref>
While the association between exercise-mediated neurogenesis and enhancement of learning remains unclear, this study could have strong implications in the fields of aging and/or [[Alzheimer's disease]].

===Effects of cannabinoids===
{{more medical citations needed|section|date=November 2016}}
Some studies have shown that the stimulation of the [[cannabinoid]]s results in the growth of new nerve cells in the hippocampus from both embryonic and adult stem cells. In 2005 a clinical study of rats at the University of Saskatchewan showed regeneration of nerve cells in the hippocampus.<ref name=Jiang05>{{cite journal |title=Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects |author1=Wen Jiang |author2=Yun Zhang |author3=Lan Xiao |author4=Jamie Van Cleemput |author5=Shao-Ping Ji |author6=Guang Bai |author7=Xia Zhang |journal=[[Journal of Clinical Investigation]] |volume=115 |issue=11 |pages=3104–16 |date=2005-11-01 |doi=10.1172/JCI25509 |pmc=1253627 |pmid=16224541}}</ref> Studies have shown that a synthetic drug resembling [[tetrahydrocanabinol|THC]], the main psychoactive ingredient in marijuana, provides some protection against [[brain inflammation]], which might result in better memory at an older age. This is due to receptors in the system that can also influence the production of new neurons.<ref>11-19-2008 [http://www.osu.edu/news/newsitem2227 Ohio State study: Scientists are high on idea that marijuana reduces memory impairment]. OSU.edu</ref>
Nonetheless, a study directed at Rutgers University demonstrated how synchronization of action potentials in the hippocampus of rats was altered after THC administration. Lack of synchronization corresponded with impaired performance in a standard test of memory.<ref>Nov 29, 2006. [http://www.physorg.com/news84048508.html Study: Marijuana may affect neuron firing]. United Press International</ref>
Recent studies indicate that a natural cannabinoid of cannabis, cannabidiol (CBD), increases adult neurogenesis while having no effect on learning. THC however impaired learning and had no effect on neurogenesis.<ref>{{cite journal |last1=Wolf |first1=Susanne A. |last2=Bick-Sander |first2=Anika |last3=Fabel |first3=Klaus |last4=Leal-Galicia |first4=Perla |last5=Tauber |first5=Svantje |last6=Ramirez-Rodriguez |first6=Gerardo |last7=Müller |first7=Anke |last8=Melnik |first8=Andre |last9=Waltinger |first9=Tim P. |last10=Ullrich |first10=Oliver |last11=Kempermann |first11=Gerd |title=Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis |journal=Cell Communication and Signaling |year=2010 |volume=8 |issue=1 |pages=12 |doi=10.1186/1478-811X-8-12 |pmid=20565726 |pmc=2898685 |doi-access=free }}</ref> 
A greater CBD to THC ratio in hair analyses of cannabis users correlates with protection against gray matter reduction in the right hippocampus.<ref>{{cite journal |last1=Demirakca |first1=T. |last2=Sartorius |first2=A. |last3=Ende |first3=G. |last4=Meyer |first4=N. |last5=Welzel |first5=H. |last6=Skopp |first6=G. |last7=Mann |first7=K. |last8=Hermann |first8=D. |doi=10.1016/j.drugalcdep.2010.09.020 |title=Diminished gray matter in the hippocampus of cannabis users: Possible protective effects of cannabidiol |journal=Drug and Alcohol Dependence |volume=114 |issue=2–3 |pages=242–5 |year=2010 |pmid=21050680 }}</ref> CBD has also been observed to attenuate the deficits in prose recall and visuo-spatial associative memory of those currently under the influence of cannabis,<ref>{{cite journal |last1=Wright |first1=M. J. |last2=Vandewater |first2=S. A. |last3=Taffe |first3=M. A. |doi=10.1111/bph.12199 |title=Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ9tetrahydrocannabinol |journal=British Journal of Pharmacology |volume=170 |issue=7 |pages=1365–73 |year=2013 |pmid=23550724 |pmc=3838683}}</ref><ref>{{cite journal |last1=Morgan |first1=C. J. A. |last2=Schafer |first2=G. |last3=Freeman |first3=T. P. |last4=Curran |first4=H. V. |title=Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: Naturalistic study |doi=10.1192/bjp.bp.110.077503 |journal=The British Journal of Psychiatry |volume=197 |issue=4 |pages=285–290 |year=2010 |pmid=20884951 |doi-access=free }}</ref> implying neuroprotective effects against heavy THC exposure. Neurogenesis might play a role in its neuroprotective effects, but further research is required.

A few studies have reported a positive association between THC and hippocampal neurogenesis.<ref name="Biphasic effects of THC in memory a">{{cite journal |last1=Calabrese |first1=Edward J. |last2=Rubio-Casillas |first2=Alberto |title=Biphasic effects of THC in memory and cognition |journal=European Journal of Clinical Investigation |date=May 2018 |volume=48 |issue=5 |pages=e12920 |doi=10.1111/eci.12920 |pmid=29574698 |doi-access=free }}</ref><ref>{{cite journal |last1=Suliman |first1=Noor Azuin |last2=Taib |first2=Che Norma Mat |last3=Moklas |first3=Mohamad Aris Mohd |last4=Basir |first4=Rusliza |title=Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats |journal=Neurotoxicity Research |date=21 September 2017 |volume=33 |issue=2 |pages=402–411 |doi=10.1007/s12640-017-9806-x |pmc=5766723 |pmid=28933048 }}</ref> Some of them hypotethize a biphasic effect,<ref name="Biphasic effects of THC in memory a"/> some of them express that part of the negative effects could be attributable to neuroadaptation due to exposure at a specific period of life, and that it could be reversed.<ref>{{cite journal |last1=Cuccurazzu |first1=Bruna |last2=Zamberletti |first2=Erica |last3=Nazzaro |first3=Cristiano |last4=Prini |first4=Pamela |last5=Trusel |first5=Massimo |last6=Grilli |first6=Mariagrazia |last7=Parolaro |first7=Daniela |last8=Tonini |first8=Raffaella |last9=Rubino |first9=Tiziana |title=Adult Cellular Neuroadaptations Induced by Adolescent THC Exposure in Female Rats Are Rescued by Enhancing Anandamide Signaling |journal=International Journal of Neuropsychopharmacology |date=November 2018 |volume=21 |issue=11 |pages=1014–24 |doi=10.1093/ijnp/pyy057 |pmc=6209859 |pmid=29982505 }}</ref>