Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 4, 2025

Autism spectrum disorder (ASD) comprises alterations in brain anatomy and physiology that ultimately affect information processing behavior. In most cases, autism is considered idiopathic, involving numerous genes whose functions are not extensively documented. We evaluated the C58/J mouse strain as an idiopathic model of ASD, emphasizing synaptic transmission basis processing. Through silico analysis, we found carries single nucleotide polymorphisms (SNPs) compared to C57BL/6J control related structure LTP induction. These SNPs have human orthologs previously associated with ASD. then assessed chemical potentiation (cLTP) synaptosomes, electrophysiological properties hippocampal CA3 cells, induction ex-vivo slices. An increased proportion synaptosomes expressing GluA1 subunit AMPA receptor Nrx1β membrane was strain, but mice, after cLTP Additionally, several pyramidal cells communication were altered. Behaviorally, mice exhibited hyperactivity subtle memory changes. Our results demonstrate ASD exhibits from cellular circuitry behavioral levels.

Язык: Английский

Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism

Hormones and Behavior, Год журнала: 2024, Номер 164, С. 105593 - 105593

Опубликована: Июнь 22, 2024

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence endocrine reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore health disparities ASD using an animal model autism, C58/J inbred mouse strain, with focus performance hormonal profiles compared C57BL/6J control strain. Our findings revealed that estrous cycle disrupted, evidenced lower frequency complete cycles lack cyclical release estradiol progesterone mice. also exhibited poor several parameters, including lifespan fertility index. Furthermore, estrogen receptor alpha content showed marked decrease hypothalamus These alterations cycle, imbalances, reduced function imply dysregulation HPO Additionally, our in-silico study identified group genes involved infertility carrying single-nucleotide polymorphisms (SNPs) which human orthologs associated autism. could offer valuable insights into molecular underpinnings neuroendocrine axis disruption issues observed ASD.

Язык: Английский

Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders

Frontiers in Neural Circuits, Год журнала: 2024, Номер 18

Опубликована: Дек. 23, 2024

Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and communication, along with restricted repetitive behaviors. Both genetic environmental factors contribute to ASD, prenatal exposure valproic acid (VPA) nicotine being linked increased risk. Impaired adult hippocampal neurogenesis, particularly the ventral region, thought play role observed ASD. Methods In this study, we investigated behavior neurogenesis C57BL/6J mice prenatally exposed VPA or nicotine, as well genetically modified ASD models, including IQSEC2 knockout (KO) NLGN3-R451C knock-in (KI) mice. Sociability novelty preference were evaluated using three-chamber test. Adult was assessed BrdU DCX immunofluorescence identify newborn immature neurons. Results VPA-exposed displayed significant interaction, while nicotine-exposed exhibited mild impairment preference. KO KI demonstrated reduced hippocampus, region associated emotion. Across all mouse reduction BrdU+/NeuN+ cells hippocampus observed, dorsal remained relatively unaffected. Similar reductions DCX-positive identified VPA, mice, indicating impaired proliferation differentiation of neuronal progenitors. Discussion These findings suggest that common hallmark across models may underlie deficits. This study provides insight into region-specific neurogenic alterations pathophysiology highlights potential targets for therapeutic interventions.

Язык: Английский