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Identifying molecular mediators of environmentally enhanced neurogenesis

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Abstract

Adult hippocampal neurogenesis occurs throughout life and supports healthy brain functions. The production of new neurons decreases with age, and deficiencies in adult neurogenesis are associated with neurodevelopmental and degenerative disease. The rate of neurogenesis is dynamically sensitive to an individual’s environmental conditions and experiences, and certain stimuli are known robustly to enhance neurogenesis in rodent models, including voluntary exercise, enriched environment, and electroconvulsive shock. In these models, information about an organism’s environment and physiological state are relayed to neurogenic cell types within the hippocampus through a series of tissue and cellular interfaces, ultimately eliciting a neurogenic response from neural stem cells and newborn neurons. Therefore, an understanding of the way that novel genes and proteins act in specific cell types within this circuit-level context is of scientific and therapeutic value. Several well-studied neurotrophic factors have been implicated in environmentally enhanced neurogenesis. This review highlights recently discovered, novel molecular mediators of neurogenesis in response to environmental cues and summarizes the contribution of advanced, large-scale gene expression and function assessment technology to past, present, and future efforts aimed at elucidating cell-type-specific molecular mediators of environmentally enhanced neurogenesis.

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References

  • Ables JL, Decarolis NA, Johnson MA, Rivera PD, Gao Z, Cooper DC, Radtke F, Hsieh J, Eisch AJ (2010) Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells. J Neurosci 30:10484–10492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aimone JB, Deng W, Gage FH (2010) Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci 14:325–337

    Article  PubMed  PubMed Central  Google Scholar 

  • Aimone JB, Deng W, Gage FH (2011) Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70:589–596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro A, Hsiang HL, Wheeler AL, Guskjolen A, Niibori Y, Shoji H, Ohira K, Richards BA, Miyakawa T, Josselyn SA, Frankland PW (2014) Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344:598–602

  • Aksay SS, Bumb JM, Janke C, Biemann R, Borucki K, Lederbogen F, Deuschle M, Sartorius A, Kranaster L (2016) Serum lipid profile changes after successful treatment with electroconvulsive therapy in major depression: a prospective pilot trial. J Affect Disord 189:85–88

    Article  CAS  PubMed  Google Scholar 

  • Allain B, Jarray R, Borriello L, Leforban B, Dufour S, Liu WQ, Pamonsinlapatham P, Bianco S, Larghero J, Hadj-Slimane R, Garbay C, Raynaud F, Lepelletier Y (2012) Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells. Cell Signal 24:214–223

    Article  CAS  PubMed  Google Scholar 

  • Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J, Bukhman YV, Young TA, Charles V, Palfreyman MG (2004) Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci 24:2667–2677

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-López MJ, Castro-Freire M, Cosín-Tomás M, Sanchez-Roige S, Lalanza JF, Del Valle J, Párrizas M, Camins A, Pallás M, Escorihuela RM, Kaliman P (2013)Long-term exercise modulates hippocampal gene expression in senescent female mice.J Alzheimers Dis 33:1177–1190

    PubMed  Google Scholar 

  • Balu DT, Lucki I (2009) Adult hippocampal neurogenesis: regulation, functional implications, and contribution to disease pathology. Neurosci Biobehav Rev 33:232–252

    Article  PubMed  Google Scholar 

  • Beckervordersandforth R, Ebert B, Schaffner I, Moss J, Fiebig C, Shin J, Moore DL, Ghosh L, Trinchero MF, Stockburger C, Friedland K, Steib K, Wittgenstein J von, Keiner S, Redecker C, Holter SM, Xiang W, Wurst W, Jagasia R, Schinder AF, Ming GL, Toni N, Jessberger S, Song H, Lie DC (2017) Role of mitochondrial metabolism in the control of early lineage progression and aging phenotypes in adult hippocampal neurogenesis. Neuron 93:1518

  • Boitard C, Etchamendy N, Sauvant J, Aubert A, Tronel S, Marighetto A, Laye S, Ferreira G (2012) Juvenile, but not adult exposure to high-fat diet impairs relational memory and hippocampal neurogenesis in mice. Hippocampus 22:2095–2100

    Article  CAS  PubMed  Google Scholar 

  • Bolijn SL, Paul J (2015) How the body talks to the brain; peripheral mediators of physical activity-induced proliferation in the adult hippocampus. Brain Plasticity 1:5–27

    Article  Google Scholar 

  • Brown J, Cooper-Kuhn CM, Kempermann G, Praag H van, Winkler J, Gage FH, Kuhn HG (2003) Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur J Neurosci 17:2042–2046

  • Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924

    Article  CAS  PubMed  Google Scholar 

  • Chabry J, Nicolas S, Cazareth J, Murris E, Guyon A, Glaichenhaus N, Heurteaux C, Petit-Paitel A (2015) Enriched environment decreases microglia and brain macrophages inflammatory phenotypes through adiponectin-dependent mechanisms: relevance to depressive-like behavior. Brain Behav Immun 50:275–287

    Article  CAS  PubMed  Google Scholar 

  • Chae CH, Kim HT (2009) Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats. Neurochem Int 55:208–213

    Article  CAS  PubMed  Google Scholar 

  • Chancey JH, Adlaf EW, Sapp MC, Pugh PC, Wadiche JI, Overstreet-Wadiche LS (2013) GABA depolarization is required for experience-dependent synapse unsilencing in adult-born neurons. J Neurosci 33:6614–6622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Christian KM, Song H, Ming GL (2014) Functions and dysfunctions of adult hippocampal neurogenesis. Annu Rev Neurosci 37:243–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark PJ, Kohman RA, Miller DS, Bhattacharya TK, Haferkamp EH, Rhodes JS (2010) Adult hippocampal neurogenesis and c-Fos induction during escalation of voluntary wheel running in C57BL/6J mice. Behav Brain Res 213:246–252

    Article  PubMed  PubMed Central  Google Scholar 

  • Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P, Jessberger S, Saksida LM, Barker RA, Gage FH, Bussey TJ (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325:210–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clemenson GD, Deng W, Gage FH (2015) Environmental enrichment and neurogenesis: from mice to humans. Curr Opin Behav Sci 4:56–62

    Article  Google Scholar 

  • Conti B, Maier R, Barr AM, Morale MC, Lu X, Sanna PP, Bilbe G, Hoyer D, Bartfai T (2007) Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine. Mol Psychiatry 12:167–189

    Article  CAS  PubMed  Google Scholar 

  • Cotman CW, Berchtold NC (2002) Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 25:295–301

    Article  CAS  PubMed  Google Scholar 

  • Czeh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Muller MB, Toschi N, Fuchs E, Keck ME (2002) Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry 52:1057–1065

    Article  CAS  PubMed  Google Scholar 

  • Darcy MJ, Trouche S, Jin SX, Feig LA (2014a) Age-dependent role for Ras-GRF1 in the late stages of adult neurogenesis in the dentate gyrus. Hippocampus 24:315–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Darcy MJ, Trouche S, Jin SX, Feig LA (2014b) Ras-GRF2 mediates long-term potentiation, survival, and response to an enriched environment of newborn neurons in the hippocampus. Hippocampus 24:1317–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Lucia C, Rinchon A, Olmos-Alonso A, Riecken K, Fehse B, Boche D, Perry VH, Gomez-Nicola D (2016) Microglia regulate hippocampal neurogenesis during chronic neurodegeneration. Brain Behav Immun 55:179–190

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Deng W, Aimone JB, Gage FH (2010) New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11:339–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dieni CV, Chancey JH, Overstreet-Wadiche LS (2012) Dynamic functions of GABA signaling during granule cell maturation. Front Neural Circ 6:113

    Google Scholar 

  • Donovan MH, Yazdani U, Norris RD, Games D, German DC, Eisch AJ (2006) Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease. J Comp Neurol 495:70–83

    Article  PubMed  Google Scholar 

  • Dostes S, Dubreucq S, Ladeveze E, Marsicano G, Abrous DN, Chaouloff F, Koehl M (2016) Running per se stimulates the dendritic arbor of newborn dentate granule cells in mouse hippocampus in a duration-dependent manner. Hippocampus 26:282–288

    Article  PubMed  Google Scholar 

  • Dranovsky A, Hen R (2006) Hippocampal neurogenesis: regulation by stress and antidepressants. Biol Psychiatry 59:1136–1143

    Article  CAS  PubMed  Google Scholar 

  • Dumitru I, Neitz A, Alfonso J, Monyer H (2017) Diazepam binding inhibitor promotes stem cell expansion controlling environment-dependent neurogenesis. Neuron 94:e125

    Article  CAS  Google Scholar 

  • Embury CM, Dyavarshetty B, Lu Y, Wiederin JL, Ciborowski P, Gendelman HE, Kiyota T (2016) Cathepsin B improves ss-amyloidosis and learning and memory in models of Alzheimer's disease. J Neuroimmune Pharmacol 12:340–352

    Article  PubMed  PubMed Central  Google Scholar 

  • Fan C, Zhao Y, Mao X, Miao Y, Lin X, Jiang G, Zhang X, Han Q, Luan L, Wang E (2014) Armc8 expression was elevated during atypia-to-carcinoma progression and associated with cancer development of breast carcinoma. Tumour Biol 35:11337–11343

    Article  CAS  PubMed  Google Scholar 

  • Fang ZH, Lee CH, Seo MK, Cho H, Lee JG, Lee BJ, Park SW, Kim YH (2013) Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats. Neurosci Res 76:187–194

    Article  CAS  PubMed  Google Scholar 

  • Farmer J, Zhao X, Praag H van, Wodtke K, Gage FH, Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124:71–79

  • Feig LA (2011) Regulation of neuronal function by Ras-GRF exchange factors. Genes Cancer 2:306–319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferguson MA, White LJ, McCoy S, Kim HW, Petty T, Wilsey J (2004) Plasma adiponectin response to acute exercise in healthy subjects. Eur J Appl Physiol 91:324–329

    Article  CAS  PubMed  Google Scholar 

  • Fordyce DE, Farrar RP (1991) Enhancement of spatial learning in F344 rats by physical activity and related learning-associated alterations in hippocampal and cortical cholinergic functioning. Behav Brain Res 46:123–133

    Article  CAS  PubMed  Google Scholar 

  • Fowler CD, Liu Y, Ouimet C, Wang Z (2002) The effects of social environment on adult neurogenesis in the female prairie vole. J Neurobiol 51:115–128

    Article  PubMed  Google Scholar 

  • Frankland PW, Kohler S, Josselyn SA (2013) Hippocampal neurogenesis and forgetting. Trends Neurosci 36:497–503

    Article  CAS  PubMed  Google Scholar 

  • Funk JA, Gohlke J, Kraft AD, McPherson CA, Collins JB, Jean Harry G (2011) Voluntary exercise protects hippocampal neurons from trimethyltin injury: possible role of interleukin-6 to modulate tumor necrosis factor receptor-mediated neurotoxicity.Brain Behav Immun 25:1063–1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Y, Wang F, Eisinger BE, Kelnhofer LE, Jobe EM, Zhao X (2017) Integrative single-cell transcriptomics reveals molecular networks defining neuronal maturation during postnatal neurogenesis. Cereb Cortex 27:2064–2077

    PubMed  Google Scholar 

  • Garrett L, Lie DC, Hrabe de Angelis M, Wurst W, Holter SM (2012) Voluntary wheel running in mice increases the rate of neurogenesis without affecting anxiety-related behaviour in single tests. BMC Neurosci 13:61

    Article  PubMed  PubMed Central  Google Scholar 

  • Ge S, Pradhan DA, Ming GL, Song H (2007) GABA sets the tempo for activity-dependent adult neurogenesis. Trends Neurosci 30:1–8

    Article  PubMed  CAS  Google Scholar 

  • Gibbons TE, Pence BD, Petr G, Ossyra JM, Mach HC, Bhattacharya TK, Perez S, Martin SA, McCusker RH, Kelley KW, Rhodes JS, Johnson RW, Woods JA (2014) Voluntary wheel running, but not a diet containing (−)-epigallocatechin-3-gallate and beta-alanine, improves learning, memory and hippocampal neurogenesis in aged mice. Behav Brain Res 272:131–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gould E, Tanapat P (1999) Stress and hippocampal neurogenesis. Biol Psychiatry 46:1472–1479

    Article  CAS  PubMed  Google Scholar 

  • Gould E, Tanapat P, Rydel T, Hastings N (2000) Regulation of hippocampal neurogenesis in adulthood. Biol Psychiatry 48:715–720

    Article  CAS  PubMed  Google Scholar 

  • Griffin EW, Bechara RG, Birch AM, Kelly AM (2009) Exercise enhances hippocampal-dependent learning in the rat: evidence for a BDNF-related mechanism. Hippocampus 19:973–980

    Article  CAS  PubMed  Google Scholar 

  • Guerrieri D, Praag H van (2015) Exercise-mimetic AICAR transiently benefits brain function. Oncotarget 6:18293–18313

  • Guo JU, Ma DK, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer JA, Eaves HL, Xie B, Ford E, Zhang K, Ming GL, Gao Y, Song H (2011) Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat Neurosci 14:1345–1351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gusdon AM, Callio J, Distefano G, O'Doherty RM, Goodpaster BH, Coen PM, Chu CT (2017) Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice. Exp Gerontol 90:1–13

    Article  CAS  PubMed  Google Scholar 

  • Hulver MW, Zheng D, Tanner CJ, Houmard JA, Kraus WE, Slentz CA, Sinha MK, Pories WJ, MacDonald KG, Dohm GL (2002) Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol Endocrinol Metab 283:E861–E865

    Article  CAS  PubMed  Google Scholar 

  • Imayoshi I, Sakamoto M, Ohtsuka T, Takao K, Miyakawa T, Yamaguchi M, Mori K, Ikeda T, Itohara S, Kageyama R (2008) Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci 11:1153–1161

    Article  CAS  PubMed  Google Scholar 

  • Inoue K, Okamoto M, Shibato J, Lee MC, Matsui T, Rakwal R, Soya H (2015) Long-term mild, rather than intense, exercise enhances adult hippocampal neurogenesis and greatly changes the transcriptomic profile of the hippocampus. PLoS One 10:e0128720

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Intlekofer KA, Cotman CW (2013) Exercise counteracts declining hippocampal function in aging and Alzheimer's disease. Neurobiol Dis 57:47–55

    Article  CAS  PubMed  Google Scholar 

  • Ji JF, Ji SJ, Sun R, Li K, Zhang Y, Zhang LY, Tian Y (2014) Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway. Biochem Biophys Res Commun 443:646–651

    Article  CAS  PubMed  Google Scholar 

  • Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, Logvinova A, Greenberg DA (2003) Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2:175–183

    Article  CAS  PubMed  Google Scholar 

  • Johnson RA, Mitchell GS (2003) Exercise-induced changes in hippocampal brain-derived neurotrophic factor and neurotrophin-3: effects of rat strain. Brain Res 983:108–114

    Article  CAS  PubMed  Google Scholar 

  • Johnson RA, Rhodes JS, Jeffrey SL, Garland T Jr, Mitchell GS (2003) Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience 121:1–7

    Article  PubMed  CAS  Google Scholar 

  • Jun H, Hussaini SM, Cho CH, Welby J, Jang MH (2015) Gadd45b mediates electroconvulsive shock induced proliferation of hippocampal neural stem cells. Brain Stimul 8:1021–1024

    Article  PubMed  PubMed Central  Google Scholar 

  • Kempermann G, Krebs J, Fabel K (2008) The contribution of failing adult hippocampal neurogenesis to psychiatric disorders. Curr Opin Psychiatr 21:290–295

    Article  Google Scholar 

  • Kempermann G, Song H, Gage FH (2015) Neurogenesis in the adult hippocampus. Cold Spring Harb Perspect Biol 7:a018812

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Keyvani K, Sachser N, Witte OW, Paulus W (2004) Gene expression profiling in the intact and injured brain following environmental enrichment. J Neuropathol Exp Neurol 63:598–609

    Article  CAS  PubMed  Google Scholar 

  • Klempin F, Kempermann G (2007) Adult hippocampal neurogenesis and aging. Eur Arch Psychiatry Clin Neurosci 257:271–280

    Article  PubMed  Google Scholar 

  • Kobilo T, Liu QR, Gandhi K, Mughal M, Shaham Y, Praag H van (2011) Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learn Mem 18:605–609

  • Kohman RA, Rodriguez-Zas SL, Southey BR, Kelley KW, Dantzer R, Rhodes JS (2011) Voluntary wheel running reverses age-induced changes in hippocampal gene expression. PLoS One 6:e22654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G (2006) Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 27:1505–1513

    Article  PubMed  Google Scholar 

  • Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033

    CAS  PubMed  Google Scholar 

  • Kuwabara T, Hsieh J, Muotri A, Yeo G, Warashina M, Lie DC, Moore L, Nakashima K, Asashima M, Gage FH (2009) Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci 12:1097–1105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lacar B, Linker SB, Jaeger BN, Krishnaswami S, Barron J, Kelder M, Parylak S, Paquola A, Venepally P, Novotny M, O'Connor C, Fitzpatrick C, Erwin J, Hsu JY, Husband D, McConnell MJ, Lasken R, Gage FH (2016) Nuclear RNA-seq of single neurons reveals molecular signatures of activation. Nat Commun 7:11022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VM, Hersh LB, Sapolsky RM, Mirnics K, Sisodia SS (2005) Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 120:701–713

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Duan W, Mattson MP (2002a) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367–1375

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Seroogy KB, Mattson MP (2002b) Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J Neurochem 80:539–547

    Article  CAS  PubMed  Google Scholar 

  • Lee MC, Rakwal R, Shibato J, Inoue K, Chang H, Soya H (2014) DNA microarray-based analysis of voluntary resistance wheel running reveals novel transcriptome leading robust hippocampal plasticity. Physiol Rep 2:e12206

  • Leuner B, Gould E (2010) Structural plasticity and hippocampal function. Annu Rev Psychol 61:C111–C113

    Article  Google Scholar 

  • Lieberwirth C, Liu Y, Jia X, Wang Z (2012) Social isolation impairs adult neurogenesis in the limbic system and alters behaviors in female prairie voles. Horm Behav 62:357–366

    Article  PubMed  PubMed Central  Google Scholar 

  • Lindqvist A, Mohapel P, Bouter B, Frielingsdorf H, Pizzo D, Brundin P, Erlanson-Albertsson C (2006) High-fat diet impairs hippocampal neurogenesis in male rats. Eur J Neurol 13:1385–1388

    Article  CAS  PubMed  Google Scholar 

  • Littlefield AM, Setti SE, Priester C, Kohman RA (2015) Voluntary exercise attenuates LPS-induced reductions in neurogenesis and increases microglia expression of a proneurogenic phenotype in aged mice. J Neuroinflammation 12:138

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Llorens-Martin M, Teixeira CM, Jurado-Arjona J, Rakwal R, Shibato J, Soya H, Avila J (2016) Retroviral induction of GSK-3beta expression blocks the stimulatory action of physical exercise on the maturation of newborn neurons. Cell Mol Life Sci 73:3569–3582

    Article  CAS  PubMed  Google Scholar 

  • Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (2009) Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074–1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madsen TM, Treschow A, Bengzon J, Bolwig TG, Lindvall O, Tingstrom A (2000) Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry 47:1043–1049

    Article  CAS  PubMed  Google Scholar 

  • Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110

    CAS  PubMed  Google Scholar 

  • Molteni R, Ying Z, Gomez-Pinilla F (2002) Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. Eur J Neurosci 16:1107–1116

    Article  PubMed  Google Scholar 

  • Monteiro BM, Moreira FA, Massensini AR, Moraes MF, Pereira GS (2014) Enriched environment increases neurogenesis and improves social memory persistence in socially isolated adult mice. Hippocampus 24:239–248

    Article  PubMed  Google Scholar 

  • Moon HY, Becke A, Berron D, Becker B, Sah N, Benoni G, Janke E, Lubejko ST, Greig NH, Mattison JA, Duzel E, van Praag H (2016) Running-induced systemic Cathepsin B secretion is associated with memory function. Cell Metab 24:332–340

    Article  CAS  PubMed  Google Scholar 

  • Mu Y, Gage FH (2011) Adult hippocampal neurogenesis and its role in Alzheimer's disease. Mol Neurodegener 6:85

    Article  PubMed  PubMed Central  Google Scholar 

  • Neeper SA, Gomez-Pinilla F, Choi J, Cotman CW (1996) Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 726:49–56

    Article  CAS  PubMed  Google Scholar 

  • Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman RS (2003) Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors. J Neurosci 23:10841–10851

    CAS  PubMed  Google Scholar 

  • Nicolas S, Veyssiere J, Gandin C, Zsurger N, Pietri M, Heurteaux C, Glaichenhaus N, Petit-Paitel A, Chabry J (2015) Neurogenesis-independent antidepressant-like effects of enriched environment is dependent on adiponectin. Psychoneuroendocrinology 57:72–83

    Article  CAS  PubMed  Google Scholar 

  • O'Connor RM, Grenham S, Dinan TG, Cryan JF (2013) microRNAs as novel antidepressant targets: converging effects of ketamine and electroconvulsive shock therapy in the rat hippocampus. Int J Neuropsychopharmacol 16:1885–1892

    Article  PubMed  CAS  Google Scholar 

  • Okamoto M, Inoue K, Iwamura H, Terashima K, Soya H, Asashima M, Kuwabara T (2011) Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis. FASEB J 25:3570–3582

    Article  CAS  PubMed  Google Scholar 

  • Okaty BW, Sugino K, Nelson SB (2011) Cell type-specific transcriptomics in the brain. J Neurosci 31:6939–6943

  • Olson AK, Eadie BD, Ernst C, Christie BR (2006) Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus 16:250–260

    Article  CAS  PubMed  Google Scholar 

  • Opendak M, Gould E (2015) Adult neurogenesis: a substrate for experience-dependent change. Trends Cogn Sci 19:151–161

    Article  PubMed  Google Scholar 

  • Overall RW, Walker TL, Fischer TJ, Brandt MD, Kempermann G (2016) Different mechanisms must be considered to explain the increase in hippocampal neural precursor cell proliferation by physical activity. Front Neurosci 10:362

    Article  PubMed  PubMed Central  Google Scholar 

  • Overstreet Wadiche L, Bromberg DA, Bensen AL, Westbrook GL (2005) GABAergic signaling to newborn neurons in dentate gyrus. J Neurophysiol 94:4528–4532

    Article  PubMed  CAS  Google Scholar 

  • Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3:715–727

    Article  CAS  PubMed  Google Scholar 

  • Pandey MK, DeGrado TR (2016) Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Theranostics 6:571–593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ploski JE, Newton SS, Duman RS (2006) Electroconvulsive seizure-induced gene expression profile of the hippocampus dentate gyrus granule cell layer. J Neurochem 99:1122–1132

    Article  CAS  PubMed  Google Scholar 

  • Poirion OB, Zhu X, Ching T, Garmire L (2016) Single-cell transcriptomics bioinformatics and computational challenges. Front Genet 7:163

    Article  PubMed  PubMed Central  Google Scholar 

  • Praag H van (2008) Neurogenesis and exercise: past and future directions. Neuromolecular Med 10:128–140

  • Praag H van, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270

  • Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, Tsien JZ, Hu Y (2000) Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci U S A 97:12880–12884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Redila VA, Christie BR (2006) Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus. Neuroscience 137:1299–1307

    Article  CAS  PubMed  Google Scholar 

  • Reshef R, Kreisel T, Beroukhim Kay D, Yirmiya R (2014) Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis. Brain Behav Immun 41:239–250

    Article  CAS  PubMed  Google Scholar 

  • Richetin K, Moulis M, Millet A, Arrazola MS, Andraini T, Hua J, Davezac N, Roybon L, Belenguer P, Miquel MC, Rampon C (2017) Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer's disease. Neurobiol Dis 102:113–124

    Article  CAS  PubMed  Google Scholar 

  • Russo-Neustadt A, Beard RC, Cotman CW (1999) Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology 21:679–682

    Article  CAS  PubMed  Google Scholar 

  • Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nat Neurosci 10:1110–1115

    Article  CAS  PubMed  Google Scholar 

  • Schloesser RJ, Orvoen S, Jimenez DV, Hardy NF, Maynard KR, Sukumar M, Manji HK, Gardier AM, David DJ, Martinowich K (2015) Antidepressant-like effects of electroconvulsive seizures require adult neurogenesis in a neuroendocrine model of depression. Brain Stimul 8:862–867

    Article  PubMed  PubMed Central  Google Scholar 

  • Scott BW, Wojtowicz JM, Burnham WM (2000) Neurogenesis in the dentate gyrus of the rat following electroconvulsive shock seizures. Exp Neurol 165:231–236

    Article  CAS  PubMed  Google Scholar 

  • Shin J, Berg DA, Zhu Y, Shin JY, Song J, Bonaguidi MA, Enikolopov G, Nauen DW, Christian KM, Ming GL, Song H (2015) Single-cell RNA-Seq with waterfall reveals molecular cascades underlying adult neurogenesis. Cell Stem Cell 17:360–372

    Article  CAS  PubMed  Google Scholar 

  • Sierra A, Beccari S, Diaz-Aparicio I, Encinas JM, Comeau S, Tremblay ME (2014) Surveillance, phagocytosis, and inflammation: how never-resting microglia influence adult hippocampal neurogenesis. Neural Plastic 2014:610343

    Article  CAS  Google Scholar 

  • Sierra A, Encinas JM, Deudero JJ, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, Tsirka SE, Maletic-Savatic M (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7:483–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song J, Crowther AJ, Olsen RHJ, Song H, G-l M (2014) A diametric mode of neuronal circuitry-neurogenesis coupling in the adult hippocampus via parvalbumin interneurons. Neurogenesis 1:e29949

    Article  Google Scholar 

  • Song J, Sun J, Moss J, Wen Z, Sun GJ, Hsu D, Zhong C, Davoudi H, Christian KM, Toni N, Ming GL, Song H (2013) Parvalbumin interneurons mediate neuronal circuitry-neurogenesis coupling in the adult hippocampus. Nat Neurosci 16:1728–1730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stangl D, Thuret S (2009) Impact of diet on adult hippocampal neurogenesis. Genes Nutr 4:271–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steib K, Schaffner I, Jagasia R, Ebert B, Lie DC (2014) Mitochondria modify exercise-induced development of stem cell-derived neurons in the adult brain. J Neurosci 34:6624–6633

    Article  CAS  PubMed  Google Scholar 

  • Stranahan AM, Khalil D, Gould E (2006) Social isolation delays the positive effects of running on adult neurogenesis. Nat Neurosci 9:526–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stranahan AM, Khalil D, Gould E (2007) Running induces widespread structural alterations in the hippocampus and entorhinal cortex. Hippocampus 17:1017–1022

    Article  PubMed  PubMed Central  Google Scholar 

  • Stranahan AM, Lee K, Becker KG, Zhang Y, Maudsley S, Martin B, Cutler RG, Mattson MP (2010) Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice.Neurobiol Aging 31:1937–1949

    Article  CAS  PubMed  Google Scholar 

  • Suzuki H, Kanagawa D, Nakazawa H, Tawara-Hirata Y, Kogure Y, Shimizu-Okabe C, Takayama C, Ishikawa Y, Shiosaka S (2014) Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments. Front Cell Neurosci 8:420

    PubMed  PubMed Central  Google Scholar 

  • Tamura H, Kawata M, Hamaguchi S, Ishikawa Y, Shiosaka S (2012) Processing of neuregulin-1 by neuropsin regulates GABAergic neuron to control neural plasticity of the mouse hippocampus. J Neurosci 32:12657–12672

    Article  CAS  PubMed  Google Scholar 

  • Tanis KQ, Duman RS, Newton SS (2008) CREB binding and activity in brain: regional specificity and induction by electroconvulsive seizure. Biol Psychiatry 63:710–720

    Article  CAS  PubMed  Google Scholar 

  • Tong L, Shen H, Perreau VM, Balazs R, Cotman CW (2001) Effects of exercise on gene-expression profile in the rat hippocampus. Neurobiol Dis 8:1046–1056

    Article  CAS  PubMed  Google Scholar 

  • Tozuka Y, Wada E, Wada K (2009) Diet-induced obesity in female mice leads to peroxidized lipid accumulations and impairment of hippocampal neurogenesis during the early life of their offspring. FASEB J 23:1920–1934

    Article  CAS  PubMed  Google Scholar 

  • Tummalapalli P, Spomar D, Gondi CS, Olivero WC, Gujrati M, Dinh DH, Rao JS (2007) RNAi-mediated abrogation of cathepsin B and MMP-9 gene expression in a malignant meningioma cell line leads to decreased tumor growth, invasion and angiogenesis. Int J Oncol 31:1039–1050

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vivar C, Potter MC, Praag H van (2013) All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis. Curr Top Behav Neurosci 15:189–210

  • Vukovic J, Colditz MJ, Blackmore DG, Ruitenberg MJ, Bartlett PF (2012) Microglia modulate hippocampal neural precursor activity in response to exercise and aging. J Neurosci 32:6435–6443

    Article  CAS  PubMed  Google Scholar 

  • Warner-Schmidt JL, Duman RS (2006) Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16:239–249

    Article  CAS  PubMed  Google Scholar 

  • Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, Ma SY, Chauhan A, Chauhan V, Bobrowicz TW, Leon M de, Louis LA, Cohen IL, London E, Brown WT, Wisniewski T (2010) The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol 119:755–770

  • Wu D, Pan W (2010) GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem Sci 35:161–168

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO (2007) Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 1162:9–18

    Article  CAS  PubMed  Google Scholar 

  • Yanpallewar SU, Barrick CA, Palko ME, Fulgenzi G, Tessarollo L (2012) Tamalin is a critical mediator of electroconvulsive shock-induced adult neuroplasticity. J Neurosci 32:2252–2262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF (2014) Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin. Proc Natl Acad Sci U S A 111:15810–15815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu JL, Ma L, Ma L, Tao YZ (2014) Voluntary wheel running enhances cell proliferation and expression levels of BDNF, IGF1 and WNT4 in dentate gyrus of adult mice. Sheng li xue bao [Acta physiologica Sinica] 66:559–568

    CAS  Google Scholar 

  • Zaben MJ, Gray WP (2013) Neuropeptides and hippocampal neurogenesis. Neuropeptides 47:431–438

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Liu T, Sun X, Mu X, Zhu G, Xiao T, Zhao M, Zhao C (2017) CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy. Behav Brain Res 322:83–91

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the NIH to X. Z. (RO1MH080434, RO1MH07897, R21NS095632), grants from the NIH to the Waisman Center (P30HD03352; U54 HD090256), and NIH NRSA to B.E.E. (F32NS094120).

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  1. Waisman Center and Department of Neuroscience, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA

    Brian E. Eisinger & Xinyu Zhao

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  1. Brian E. Eisinger
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  2. Xinyu Zhao
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Correspondence to Xinyu Zhao.

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Eisinger, B.E., Zhao, X. Identifying molecular mediators of environmentally enhanced neurogenesis. Cell Tissue Res 371, 7–21 (2018). https://doi.org/10.1007/s00441-017-2718-5

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