Exploring behavioral patterns and hippocampal neurogenesis in autism spectrum disorder mice

NIU Xiao-jie LIU Jiao ZHANG Xin-wei WANG Ze-tao YAN Ke-qi LIU Qi-yuan HAO Wan-yun ZHANG Pei-jun

Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (2) : 171-179.

PDF(9015 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(9015 KB)
Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (2) : 171-179. DOI: 10.16098/j.issn.0529-1356.2025.02.007

Exploring behavioral patterns and hippocampal neurogenesis in autism spectrum disorder mice

  • NIU  Xiao-jie1  LIU  Jiao ZHANG  Xin-wei1  WANG  Ze-tao1  YAN  Ke-qi1  LIU  Qi-yuan1  HAO  Wan-yun1  ZHANG  Pei-jun1, 2* 
Author information +
History +

Abstract

Objective  To explore the behavioral patterns and hippocampal neurogenesis of CHD8+/- mice, and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.   Methods  Genotype of wild type (WT) and CHD8+/- mice was identified. Weight measurement was conducted on both male and female mice of the WT and CHD8+/- strains. Subsequently, a battery of behavioral tests was administered, which included three-chamber test, self-grooming test, nesting test, Y-maze spontaneous alternation test,  food burial test, open-field test and light-dark transition test. Afterwards, the mice were administered 2% pentobarbital sodium (2 ml/kg) to induce anesthesia. Their brains were frozen with 4% paraformaldehyde, removed for photography and analysis to identify any alterations in brain size. Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.   Results  Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8 (CHD8) protein in both male and female mice with CHD8+/- genotype, as compared to WT mice. There were no notable disparities in body weight between male and female WT and CHD8+/- mice, as well as in brain size. The three-chamber social behavior test revealed that both male and female CHD8+/- mice had social deficiencies (P<0.05). During the open field test, there was no significant difference in the total distance moved by male and female WT and CHD8+/- mice. However, the amount of time spent in the central region was considerably lower in CHD8+/- mice compared to the WT mice (P<0.01). Furthermore, the light-dark transition test revealed that both male and female CHD8+/- mice spent considerably less time investigating the white box compared to the WT mice (P<0.05). Nevertheless, there were no notable alterations found in self-grooming, nesting, spontaneous alternation of Y-maze, and food burial experiments. In addition, Western blotting result  demonstrated a significant drop in doublecortin (DCX) expression (P<0.001), and immunofluorescent staining revealed a notable reduction in the number of DCX+ cells (P<0.01) in the hippocampus of CHD8+/- mice.   Conclusion  CHD8+/- mice exhibit social disorders and anxiety-like behaviors, with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders. 

Key words

Autism spectrum disorder / Chromodomain helicase DNA binding protein 8 / Hippocampus / Neurogenesis / Behavioral test / Mouse

Cite this article

Download Citations
NIU Xiao-jie LIU Jiao ZHANG Xin-wei WANG Ze-tao YAN Ke-qi LIU Qi-yuan HAO Wan-yun ZHANG Pei-jun. Exploring behavioral patterns and hippocampal neurogenesis in autism spectrum disorder mice[J]. Acta Anatomica Sinica. 2025, 56(2): 171-179 https://doi.org/10.16098/j.issn.0529-1356.2025.02.007

References

 [1]Lord  C, Risi S, DiLavore PS, et al. Autism from 2 to 9 years of age [J]. Arch Gen Psychiatry, 2006, 63(6): 694-701.
 [2] Thapar  A, Cooper M, Rutter M. Neurodevelopmental disorders [J]. Lancet Psychiatry, 2017, 4(4): 339-346.
 [3] Maenner  MJ, Shaw KA, Baio J, et al. Prevalence of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network, 11 sites, united states, 2016 [J]. MMWR Surveill Summ, 2020, 69(4): 1-12.
 [4] Kaat  AJ, Shui AM, Ghods SS, et al. Sex differences in scores on standardized measures of autism symptoms: a multisite integrative data analysis [J]. J Child Psychol Psychiatry, 2021, 62(1): 97-106.
 [5] Kissel  LT, Werling DM. Neural transcriptomic analysis of sex differences in autism spectrum disorder: current insights and future directions [J]. Biol Psychiatry, 2022, 91(1): 53-60.
 [6] Chan  MMY, Han YMY. Differential mirror neuron system (mns) activation during action observation with and without social-emotional components in autism: a meta-analysis of neuroimaging studies [J]. Mol Autism, 2020, 11(1): 72.
 [7] Pitcher  D, Japee S, Rauth L, et al. The superior temporal sulcus is causally connected to the amygdala: a combined TBS-fMRI study [J]. J Neurosci, 2017, 37(5): 1156-1161.
 [8] Lord  C, Elsabbagh M, Baird G, et al. Autism spectrum disorder [J]. Lancet, 2018, 392(10146): 508-520.
 [9] Bourgeron  T. From the genetic architecture to synaptic plasticity in autism spectrum disorder [J]. Nat Rev Neurosci, 2015, 16(9): 551-563.
 [10] Gage  FH. Adult neurogenesis in neurological diseases [J]. Science, 2021, 374(6571): 1049-1050.
 [11] Shiraishi  T, Katayama Y, Nishiyama M, et al. The complex etiology of autism spectrum disorder due to missense mutations of CHD8 [J]. Mol Psychiatry, 2024. 29(7):2145-2160.
 [12] Liu  XQ, Niu XJ, Wang BH, et al. 18α?glycyrrhetinic acid promoting neural stem cells proliferation through antioxidant in the subventricular zone of adult mice [J]. Acta Anatomica Sinica, 2022, 53(1): 11-18. (in Chinese) 
刘雪芹, 牛晓洁, 王必慧, 等. 18α-甘草次酸通过抗氧化作用促进成年小鼠室管膜下区神经干细胞增殖 [J]. 解剖学报, 2022, 53(1): 11-18.
 [13] Barnard  RA, Pomaville MB, O’Roak BJ. Mutations and modeling of the chromatin remodeler CHD8 define an emerging autism etiology [J]. Front Neurosci, 2015, 9: 477.
 [14] Cox  KH, Rissman EF. Sex differences in juvenile mouse social behavior are influenced by sex chromosomes and social context [J]. Genes Brain Behav, 2011, 10(4): 465-472.
 [15] Ostrowski  PJ, Zachariou A, Loveday C, et al. The CHD8 overgrowth syndrome: a detailed evaluation of an emerging overgrowth phenotype in 27 patients [J]. Am J Med Genet C Semin Med Genet, 2019, 181(4): 557-564.
 [16] Jimenez  JA, Ptacek TS, Tuttle AH, et al. Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life [J]. Mol Autism, 2020, 11(1): 74.
 [17] Jung  H, Park H, Choi Y, et al. Sexually dimorphic behavior, neuronal activity, and gene expression in chd8-mutant mice [J]. Nat Neurosci, 2018, 21(9): 1218-1228.
 [18] Kawamura  A, Nishiyama M. Deletion of the autism-related gene chd8 alters activity-dependent transcriptional responses in mouse postmitotic neurons [J]. Commun Biol, 2023, 6(1): 593.
 [19] Platt  RJ, Zhou Y, Slaymaker IM, et al. Chd8 mutation leads to autistic-like behaviors and impaired striatal circuits [J]. Cell Rep, 2017, 19(2): 335-350.
 [20] Katayama  Y, Nishiyama M, Shoji H, et al. Chd8 haploinsufficiency results in autistic-like phenotypes in mice [J]. Nature, 2016, 537(7622): 675-679.
 [21] Lee  SY, Kweon H, Kang H, et al. Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors [J]. Front Mol Neurosci, 2022, 15: 1022306.
 [22] Wade  AA, Lim K, Catta-Preta R, et al. Common CHD8 genomic targets contrast with model-specific transcriptional impacts of CHD8 haploinsufficiency [J]. Front Mol Neurosci, 2018, 11: 481.
 [23] Lee  SY, Kweon H, Kang H, et al. Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes [J]. Front Mol Neurosci, 2023, 16: 1111388.
 [24] Paik  KE, Mooneyham GC. Concurrent developmental regression and neurocognitive decline in a child with de novo CHD8 gene mutation [J]. Pediatr Neurol, 2024, 154: 1-3.

PDF(9015 KB)

Accesses

Citation

Detail

Sections
Recommended

/