Objective To investigate the effects of maternal obesity and obesity resistance induced by high-fat diet on proliferation and differentiation of neural stem cells in fetal rats. Methods A total of 16 female Sprague-Dawley rats were randomly fed the control or high-fat diet for 8 weeks and then divided into three groups: control-control (CC), obesity-prone (OP) and obesity-resistant (OR), with 4 rats in each group. After mating with male rats of the same week, gestational day 17.5(GD17.5) and GD19.5 fetal rats were collected with, 4 rats in each group. The body weight and length of fetal rats were measured. The expressions of Nestin, DCX (doublecortin), NeuN (neuronal nuclei), GFAP (glial fibrillary acidic protein) and CREB-BDNF (cAMP-response element binding protein, brain-derived neurotrophic factor) signaling pathway proteins in brain tissue were analyzed by Western Blot. Results On GD17.5, compared with the CC group, body weight was increased (P<0.05), and the expressions of Nestin, CREB protein, P-CREB /CREB ratio significantly decreased in OP group (P<0.01, P<0.01, P<0.01). In the OR group, body weight and length were increased (P<0.01, P<0.01), and the expressions of Nestin, GFAP and CREB proteins significantly decreased (P<0.05, P<0.01, P<0.01). Compared with the OR group, body length was decreased (P<0.01), and the expression of Nestin protein and p-CREB/CREB ratio decreased significantly in brain tissue, while the expression of GFAP protein increased significantly in OP group (P<0.01, P<0.05, P<0.01). On GD19.5, compared with the CC group, body weight was increased (P<0.05), and the expressions of Nestin, DCX and GFAP significantly decreased in the OP group (P<0.01, P<0.05, P<0.01).In the OR group, body weight and length were increased (P<0.01, P<0.01), and the expressions of Nestin and DCX proteins decreased, while the CREB protein and p-CREB/CREB ratio significantly increased (P<0.01, P<0.01, P<0.01, P<0.01). Compared with the OR group, body length was decreased (P<0.01), and the expressions of GFAP, CREB, BDNF protein, p-CREB/CREB ratio in brain tissue significantly decreased in the OP group (P<0.05, P<0.01, P<0.05, P<0.01). Conclusion Maternal obesity and obesity resistance induced by high-fat diet can inhibit the proliferation and differentiation of neural stem cells in fetal rats, and the numbers of neural stem cells, neural progenitor cell and astrocytes reduced.
Key words
high-fat diet /
rat /
pregnancy /
obesity /
obesity resistant /
neurodevelopment
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] 房红芸,郭齐雅,琚腊红,等.2010—2013年中国15~49岁育龄妇女体重认知及控制状况[J].卫生研究,2019,48:888–891,944.
[2] Marchi J, Berg M, Dencker A, et al. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews[J]. Obes Rev, 2015 16:621–638.
[3] Godfrey KM, Reynolds RM, Prescott SL, et al. Influence of maternal obesity on the long-term health of offspring[J]. Lancet Diabetes Endocrinol,2017,5:53–64.
[4] Edlow AG.Maternal obesity and neurodevelopmental and psychiatric disorders in offspring[J]. Prenat Diagn,2017,37:95–110.
[5] Zhang J, Jiao J.Molecular biomarkers for embryonic and adult neural stem cell and neurogenesis[J]. Biomed Res Int,2015,2015:727542.
[6] Stachowiak EK, Srinivasan M, Stachowiak MK, et al. Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life[J]. Metab Brain Dis,2013,28:721–725.
[7] Niculescu MD, Lupu DS.High fat diet-induced maternal obesity alters fetal hippocampal development[J]. Int J Dev Neurosci, 2009,27:627–633.
[8] Lu B, Nagappan G, Guan X, et al. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases[J]. Nat Rev Neurosci, 2013,14:401–416.
[9] Amidfar M, de Oliveira J, Kucharska E, et al. The role of CREB and BDNF in neurobiology and treatment of Alzheimer's disease[J]. Life Sci,2020, 257:118020.
[10] Kowiaski P, Lietzau G, Czuba E, et al. BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity[J]. Cell Mol Neurobiol,2018,38:579–593.
[11] Blüher M.Obesity: global epidemiology and pathogenesis[J]. Nat Rev Endocrinol,2019,15:288–298.
[12] Buettner R, Schölmerich J, Bollheimer LC.High-fat diets: modeling the metabolic disorders of human obesity in rodents[J]. Obesity (Silver Spring),2007,15:798–808.
[13] Levin BE, Dunn-Meynell AA, McMinn JE, et al. A new obesity-prone, glucose-intolerant rat strain (F.DIO)[J]. Am J Physiol Regul Integr Comp Physiol,2003, 285:R1184–R1191.
[14] Levin BE, Dunn-Meynell AA.Defense of body weight depends on dietary composition and palatability in rats with diet-induced obesity[J]. Am J Physiol Regul Integr Comp Physiol,2002,282:R46–R54.
[15] Hariri N, Thibault L.High-fat diet-induced obesity in animal models[J]. Nutr Res Rev,2010,23:270–299.
[16] Gage FH.Mammalian neural stem cells[J]. Science,2000,287:1433–1438.
[17] Bernal A, Arranz L.Nestin-expressing progenitor cells: function, identity and therapeutic implications[J]. Cell Mol Life Sci,2018,75:2177–2195.
[18] Sorrells SF, Paredes MF, Zhang Z, et al. Positive controls in adults and children support that very few, if any, new neurons are born in the adult human hippocampus[J]. J Neurosci,2021,41:2554–2565.
[19] Duan W, Zhang YP, Hou Z, et al. Novel insights into neun: from neuronal marker to splicing regulator[J]. Mol Neurobiol,2016,53:1637–1647.
[20] Hol EM, Pekny M.Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system[J]. Curr Opin Cell Biol,2015,32:121–130.
[21] Niklison-Chirou MV, Agostini M, Amelio I, et al. Regulation of adult neurogenesis in mammalian brain[J]. Int J Mol Sci,2020,21:4869.
[22] Bond AM, Ming GL, Song H.Ontogeny of adult neural stem cells in the mammalian brain[J]. Curr Top Dev Biol, 2021,142:67–98.
[23] Hu X, An J, Ge Q, et al. Maternal high-fat diet reduces type-2 neural stem cells and promotes premature neuronal differentiation during early postnatal development[J]. Nutrients,2022,14:2813.
[24] Walton MR, Dragunow I.Is CREB a key to neuronal survival?[J]. Trends Neurosci,2000,23:48–53.
[25] Scharfman H, Goodman J, Macleod A, et al. Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats[J]. Exp Neurol, 2005,192:348–356.
[26] Gao X, Smith GM, Chen J.Impaired dendritic development and synaptic formation of postnatal-born dentate gyrus granular neurons in the absence of brain-derived neurotrophic factor signaling[J]. Exp Neurol, 2009,215:178–190.
[27] Tozuka Y, Kumon M, Wada E, et al. Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring[J]. Neurochem Int, 2010,57:235–247.
[28] Tozuka Y, Wada E, Wada K.Diet-induced obesity in female mice leads to peroxidized lipid accumulations and impairment of hippocampal neurogenesis during the early life of their offspring[J]. FASEB J,2009,23:1920–1934.
