Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation

DENG Ying-Cheng; NIU Lei; XIAO Yu-Hua; SUN Qiu-Min; XU Xuan; WAN Wei

doi:10.16098/j.issn.0529-1356.2022.02.003

PDF(1075 KB)

Acta Anatomica Sinica ›› 2022, Vol. 53 ›› Issue (2) : 155-159. DOI: 10.16098/j.issn.0529-1356.2022.02.003

Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation

DENG Ying-cheng¹ NIU lei¹ XIAO Yu-hua¹ XU Xuan¹ SUN Qiu-ming² WAN Wei^1,3*

Author information +

History +

Abstract

Objective To investigate the effect of hippocampal brain derived neurotrophic factor precursor (proBDNF) in cognitive dysfuction induced by social isolation. Methods Thirty C57BL/6 J male mice (4-week old) were randomly divided into group house (GH，n=15) and socially isolated (SI，n=15) groups. The GH group (5 mice/cage) and SI group (1 mice/cage) were reared separately under the same conditions. The novel object recognition test and the novel place recognition test were used to evaluate the cognitive function. The expression of BDNF mRNA in the hippocampus was detected by Real-time PCR. The expression of BDNF and proBDNF in hippocampus was detected by Western blotting. Matrix metallopeptidase-9 (MMP-9) and tissue plasminogen activator (tPA) were extracellular enzymes that catalyzed the transformation of proBDNF into mature BDNF. Expression of MMP-9 and tPA mRNA in the hippocampus were detected by Real-time PCR. Results Compared with the GH group, the SI group showed significantly reduced discrimination ratio in the novel object recognition test and novel place recognition test. The result of Real-time PCR showed that there was no difference in the expression of BDNF mRNA between SI group and GH group. The result of Western blotting showed that the expression level of proBDNF in the hippocampus of SI group increased significantly compared with the GH group (P<0.01),and no difference in BDNF expression was found between the two groups; Compared with the GH group, the BDNF/proBDNF ratio in the hippocampus of SI group decreased. In addition, the result of Real-time PCR showed that the expression level of MMP-9 and tPA mRNA in the hippocampus of SI group decreased significantly compared with the GH group. Conclusion The social isolation-induced cognitive dysfuction in mice may be related to the up-regulation of proBDNF in the hippocampus．

Key words

Social isolation / Cognitive dysfunction / Hippocampus / Brain derived neurotrophic factor precursor / Western blotting / Mouse

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

DENG Ying-cheng NIU lei XIAO Yu-hua XU Xuan SUN Qiu-ming WAN Wei. Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation[J]. Acta Anatomica Sinica. 2022, 53(2): 155-159 https://doi.org/10.16098/j.issn.0529-1356.2022.02.003

References

［1］ Holt-Lunstad J, Smith TB, Baker M, et al. Loneliness and social isolation as risk factors for mortality: a meta-analytic review ［J］. Perspect Psychol Sci, 2015, 10(2): 227-237.

［2］ Wang B，Wu Q，Lei L，et al． Long-term social isolation inhibits autophagy activation， induces postsynaptic dysfunctions and impairs spatial memory［J］． Exp Neurol，2019，311:213-224．

［3］ Niu L，Luo ShSh，Zeng JY，et al．Effect and mechanism of caloric restriction on early social isolation-induced cognitive impairment in mice［J］．Acta Anatomica Sinica，2019,50(4)：418-422. (in Chinese)

牛磊，罗诗诗，曾佳玉，等. 热量限制改善早期社会隔离诱导的小鼠认知功能障碍［J］. 解剖学报, 2019， 50(4):418-422.

［4］ Numakawa T, Odaka H, Adachi N. Actions of brain-derived neurotrophin factor in the neurogenesis and neuronal function, and its involvement in the pathophysiology of brain diseases ［J］. Int J Mol Sci, 2018, 19(11): 3650.

［5］ Deinhardt K, Chao MV. Shaping neurons: long and short range effects of mature and proBDNF signalling upon neuronal structure ［J］. Neuropharmacology，2014，76:603-609.

［6］ Duman RS, Sanacora G, Krystal JH. Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments［J］. Neuron, 2019,102(1):75-90.

［7］ Niculescu D, Michaelsen-Preusse K, Güner ü, et al. A BDNF-mediated push pull plasticity mechanism for synaptic clustering［J］. Cell Rep, 2018,24(8): 2063-2074.

［8］ Shen T, You Y, Joseph C, et al. BDNF polymorphism: a review of its diagnostic and clinical relevance in neurodegenerative disorders［J］. Aging Dis, 2018, 9(3):523-536.

［9］ Paddock N, Sheppard P, Gardiner P. Chronic increases in daily neuromuscular activity promote changes in gene expression in small and large dorsal root ganglion neurons in rat ［J］. Neuroscience, 2018,388:171-180.

［10］ Talani G，Biggio F，Licheri V，et al． Isolation rearing reduces neuronal excitability in dentate gyrus granule cells of adolescent C57BL/6J mice: role of gabaergic tonic currents and neurosteroids［J］． Front Cell Neurosci，2016，10:158．

［11］ Sawangjit A, Oyanedel CN, Niethard N, et al. The hippocampus is crucial for forming non-hippocampal long-term memory during sleep［J］. Nature, 2018,564 (7734):109-113.

［12］ Wang Zh，Huang YJ，Nai AT，et al．Fluoxetine improved the depression-like behavior induced by chronic restraint stress by up-regulation the expression of bromodomain-containing protein 4 in hippocampus of mouse［J］．Acta Anatomica Sinica，2019，50(1):18-23．(in Chinese)

王贞，黄怡佳，乃爱桃，等．氟西汀通过上调海马内溴结构域蛋白 4 的表达改善慢性束缚应激所致小鼠的抑郁样行为［J］．解剖学报，2019，50(1):18-23．

［13］ Fone KC, Porkess MV. Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevanceto developmental neuropsychiatric disorders［J］. Neurosci Biobehav Rev, 2008, 32(6): 1087-1102.

［14］ Li L, Du Y, Li N, et al. Top-down modulation of prepulse inhibition of the startle reflex in humans and rats ［J］.Neurosci Biobehav Rev,2009,33(8): 1157-1167.

［15］ Yusufishaq S，Rosenkranz JA．Post-weaning social isolation impairs observational fear conditioning［J］． Behav Brain Res，2013，242:142-149．

［16］ Brooks SK, Webster RK, Smith LE, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence［J］. Lancet, 2020, 395 (10227):912-920.

［17］ Morley JE, Vellas B. COVID-19 and older adults［J］. J Nutr Health Aging, 2020,24(4):364-365.

［18］ Courtin E, Knapp M. Social isolation, loneliness and health in old age: a scoping review［J］. Heal Soc Care Community, 2017,25(3):799-812.

［19］ Lee S, Chan LYY, Chau AMY, et al. The experience of SARS-related stigma at Amoy Gardens［J］. Soc Sci Med, 2005,61(9):2038-2046.

［20］ Wilson RS, Krueger KR, Arnold SE, et al.Loneliness and risk of Alzheimer disease［J］. Arch Gen Psychiatry, 2007, 64(2), 234-240.

［21］ Lasley SM, Gilbert ME. Developmental thyroid hormone insufficiency reduces expression of brainderived neurotrophic factor (BDNF) in adults but not in neonates ［J］. Neurotoxicol Teratol, 2011,33(4):464-472.

［22］ Lu B, Nagappan G, Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction［J］. Handb Exp Pharmacol, 2014, 220:223-250.

［23］ Winnubst J, Cheyne JE, Niculescu D, et al. Spontaneous activity drives local synaptic plasticity in vivo［J］. Neuron, 2015,87(2):399-410.

［24］ Sun Y, Lim Y, Li F, et al. ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA ［J］. PLoS One, 2012, 7(4): e35883.