●    of special interest 

●● of outstanding interest

1.       Ming G, Song H: Adult neurogenesis in the mammalian central nervoussystem. Annu.Rev.Neurosci.2005, 28: 223-250.

2.       Toda T, Parylak SL, Linker SB, Gage FH: The role of adult hippocampal neurogenesis in brain health and disease. Mol.Psychiatry2018, : 1.

3.       Seib DR, Martin-Villalba A: Neurogenesis in the Normal Ageing Hippocampus: A Mini-Review. Gerontology2015, 61: 327-335.

4.       Apple DM, Solano-Fonseca R, Kokovay E: Neurogenesis in the aging brain. Biochem.Pharmacol.2017, 141: 77-85.

5.       Shohayeb B, Diab M, Ahmed M, Ng DCH: Factors that influence adult neurogenesis as potential therapy. Translational neurodegeneration2018, 7: 4.

6.       Weissmiller AM, Wu C: Current advances in using neurotrophic factors to treat neurodegenerative disorders. Translational neurodegeneration2012, 1: 14.

7.       Li Y, Li Y, Yang L, Zhang K, Zheng K, Wei X, Yang Q, Niu W, Zhao M, Wu Y: Silibinin exerts antidepressant effects by improving neurogenesis through BDNF/TrkB pathway. Behav.Brain Res.2018, .

8.       Tolwani R, Buckmaster P, Varma S, Cosgaya J, Wu Y, Suri C, Shooter E: BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus. Neuroscience2002, 114: 795-805.

9.       López-Doménech G, Higgs NF, Vaccaro V, Roš H, Arancibia-Cárcamo IL, MacAskill AF, Kittler JT: Loss of dendritic complexity precedes neurodegeneration in a mouse model with disrupted mitochondrial distribution in mature dendrites. Cell reports2016, 17: 317-327.

10.     Jang SW, Liu X, Yepes M, Shepherd KR, Miller GW, Liu Y, Wilson WD, Xiao G, Blanchi B, Sun YE, et al.: A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone.Proc.Natl.Acad.Sci.U.S.A.2010, 107: 2687-2692.

●This is the first study to report 7,8-dihydroxyflavone (DHF) as a potent and selective in vivoagonist of TrkB. Administration of DHF in mice activated TrkB and downstream signaling, protected neurons from apoptosis, and inhibited kainic acid-induced toxicity. 

11.     Wang X, Romine JL, Gao X, Chen J: Aging impairs dendrite morphogenesis of newborn neurons and is rescued by 7, 8‐dihydroxyflavone. Aging cell2017, 16: 304-311.

12.     Cunha C, Brambilla R, Thomas KL: A simple role for BDNF in learning and memory? Frontiers in molecular neuroscience2010, 3: 1.

13.     Zhao S, Yu A, Wang X, Gao X, Chen J: Post-injury treatment of 7, 8-dihydroxyflavone promotes neurogenesis in the hippocampus of the adult mouse.J.Neurotrauma2016, 33: 2055-2064.

14.      Guilloux J, Samuels BA, Mendez-David I, Hu A, Levinstein M, Faye C, Mekiri M, Mocaer E, Gardier AM, Hen R: S 38093, a histamine H 3 antagonist/inverse agonist, promotes hippocampal neurogenesis and improves context discrimination task in aged mice. Scientific reports2017, 7: 42946. 

●●This study showed that chronic administration of H3 antagonist S38093 reversed aged-associated decline in hippocampal neurogenesis and cognition through improving BDNF expressions. It also demonstrated the important role of vascular endothelial growth factor (VEGF) in neurogenesis enhancement.

15.     Brown RE, Reymann KG: Histamine H3 receptor‐mediated depression of synaptic transmission in the dentate gyrus of the rat in vitro. J.Physiol.(Lond.)1996, 496: 175-184.

16.     Mackowiak M, O’Neill MJ, Hicks CA, Bleakman D, Skolnick P: An AMPA receptor potentiator modulates hippocampal expression of BDNF: an in vivo study. Neuropharmacology2002, 43: 1-10.

17.     Gokul K: Oral supplements of aqueous extract of tomato seeds alleviate motor abnormality, oxidative impairments and neurotoxicity induced by rotenone in mice: relevance to Parkinson’s disease. Neurochem.Res.2014, 39: 1382-1394.

18.     Prema A, Janakiraman U, Manivasagam T, Thenmozhi AJ: Neuroprotective effect of lycopene against MPTP induced experimental Parkinson’s disease in mice. Neurosci.Lett.2015, 599: 12-19.

19.     Bae J, Han M, Shin HS, Shon D, Lee S, Shin C, Lee Y, Lee DH, Chung JH: Lycopersicon esculentum Extract Enhances Cognitive Function and Hippocampal Neurogenesis in Aged Mice. Nutrients2016, 8: 679.

20.     Jacobsen JP, Mørk A: Chronic corticosterone decreases brain-derived neurotrophic factor (BDNF) mRNA and protein in the hippocampus, but not in the frontal cortex, of the rat. Brain Res.2006, 1110: 221-225.

21.     Zhang H, Zhao Y, Wang Z: Chronic corticosterone exposure reduces hippocampal astrocyte structural plasticity and induces hippocampal atrophy in mice. Neurosci.Lett.2015, 592: 76-81.

22.     Brummelte S, Galea LA: Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats. Neuroscience2010, 168: 680-690.

23.     Lichtenwalner R, Forbes M, Bennett S, Lynch C, Sonntag W, Riddle D: Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience2001, 107: 603-613.

24.     Markowska A, Mooney M, Sonntag W: Insulin-like growth factor-1 ameliorates age-related behavioral deficits. Neuroscience1998, 87: 559-569.

25.     Pardo J, Uriarte M, Cónsole GM, Reggiani PC, Outeiro TF, Morel GR, Goya RG: Insulin‐like growth factor‐I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats. Eur.J.Neurosci.2016, 44: 2120-2128.

26.     Hu A, Yuan H, Wu L, Chen R, Chen Q, Zhang T, Wang Z, Liu P, Zhu X: The effect of constitutive over-expression of insulin-like growth factor 1 on the cognitive function in aged mice. Brain Res.2016, 1631: 204-213.

●●This study showed that overexpressing of IGF-1 restored learning and memory decline in aged mice via improving hippocampal neurogenesis, which was mediated by CaMKII and ERK signaling.  

27.     Devi L, Ohno M: Effects of levetiracetam, an antiepileptic drug, on memory impairments associated with aging and Alzheimer’s disease in mice. Neurobiol.Learn.Mem.2013, 102: 7-11.

28.     Chen BH, Yan BC, Park JH, Ahn JH, Lee DH, Kim IH, Cho J, Lee J, Kim SK, Lee B: Aripiprazole, an atypical antipsychotic drug, improves maturation and complexity of neuroblast dendrites in the mouse dentate gyrus via increasing superoxide dismutases. Neurochem.Res.2013, 38: 1980-1988.

29.     B Kharatmal S, N Singh J, S Sharma S: Rufinamide improves functional and behavioral deficits via blockade of tetrodotoxin-resistant sodium channels in diabetic neuropathy. Current neurovascular research2015, 12: 262-268.

30.     Chen BH, Ahn JH, Park JH, Song M, Kim H, Lee T, Lee JC, Kim Y, Hwang IK, Kim DW: Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB. Chem.Biol.Interact.2018, 286: 71-77.

●●This is the first study to demonstrate the effects of rufinamide on neurogenesis in the hippocampus. Rufinamide treatment in aged gerbil improved hippocampal neurogenesis and cognitive behaviour via CREB regulation, which was activated by IGF-1 binding with its receptor IGF-1R. 

31.     Song Y, Pimentel C, Walters K, Boller L, Ghiasvand S, Liu J, Staley KJ, Berdichevsky Y: Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury. Scientific reports2016, 6: 32095.

32.    Tumati S, Burger H, Martens S, van der Schouw, Yvonne T, Aleman A: Association between cognition and serum insulin-like growth factor-1 in middle-aged & older men: an 8 year follow-up study. PloS one2016, 11: e0154450

●This 8-year follow-up study suggested that in human both high and low levels of IGF-1 were associated with poor cognitive functions, indicating that human brain required optimum levels of IGF-1 to accomplish optimal functioning. 

33.     Chigogora S, Zaninotto P, Kivimaki M, Steptoe A, Batty G: Insulin-like growth factor 1 and risk of depression in older people: the English Longitudinal Study of Ageing. Translational psychiatry2016, 6: e898.

34.     Mir S, Cai W, Carlson SW, Saatman KE, Andres DA: IGF-1 mediated neurogenesis involves a novel RIT1/Akt/Sox2 cascade. Scientific reports2017, 7: 3283.

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

36.     Saraulli D, Costanzi M, Mastrorilli V, Farioli-Vecchioli S: The long run: Neuroprotective effects of physical exercise on adult neurogenesis from youth to old age. Current neuropharmacology2017, 15: 519-533.

37.     Stimpson NJ, Davison G, Javadi A: Joggin’the Noggin: Towards a Physiological Understanding of Exercise-Induced Cognitive Benefits. Neuroscience & Biobehavioral Reviews2018, .

●This review proposed a model describing possible stages involved in the mechanism of exercise-induced neurogenesis improvement. The model demonstrated that exercise increased IGF-1 and IGF-1 upregulated BDNF expression, under the regulation of CREB. 

38.     Carro E, Nunez A, Busiguina S, Torres-Aleman I: Circulating insulin-like growth factor I mediates effects of exercise on the brain. J.Neurosci.2000, 20: 2926-2933.

39.     Ahn JH, Choi JH, Park JH, Kim IH, Cho J, Lee J, Koo H, Hwangbo G, Yoo K, Lee CH: Long-term exercise improves memory deficits via restoration of myelin and microvessel damage, and enhancement of neurogenesis in the aged gerbil hippocampus after ischemic stroke. Neurorehabil.Neural Repair2016, 30: 894-905.

40.     Vanzella C, Neves JD, Vizuete AF, Aristimunha D, Kolling J, Longoni A, Gonçalves CAS, Wyse AT, Netto CA: Treadmill running prevents age-related memory deficit and alters neurotrophic factors and oxidative damage in the hippocampus of Wistar rats. Behav.Brain Res.2017, 334: 78-85.

41.     Strle K, Broussard SR, McCusker RH, Shen W, Johnson RW, Freund GG, Dantzer R, Kelley KW: Proinflammatory cytokine impairment of insulin-like growth factor I-induced protein synthesis in skeletal muscle myoblasts requires ceramide. Endocrinology2004, 145: 4592-4602.

42.     Bilkei-Gorzo A, Albayram O, Draffehn A, Michel K, Piyanova A, Oppenheimer H, Dvir-Ginzberg M, Rácz I, Ulas T, Imbeault S: A chronic low dose of Δ 9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat.Med.2017, 23: 782.

43.     Raefsky SM, Mattson MP: Adaptive responses of neuronal mitochondria to bioenergetic challenges: roles in neuroplasticity and disease resistance. Free Radical Biology and Medicine2017, 102: 203-216.

44.     Lee C, Bendriem RM, Wu WW, Shen R: 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. J.Biomed.Sci.2017, 24: 59.

45.     Huang J, Chen J: Tranylcypromine causes neurotoxicity and represses BHC110/LSD1 in Human iPSC-Derived Cerebral Organoids Model. Frontiers in neurology2017, 8: 626.