There are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is based upon the human fetal valproate spectrum disorder, which is associated with increased risk of developing ASD. This model, which displays significant social, learning, and memory alterations, has therefore been widely used to further our understanding of specific biological features of ASD. However, to date, almost all of the studies employing this model have used male rodents. To fill this knowledge gap, we evaluated sex differences for neuronal activity, morphology, and glycogen synthase kinase-3 (GSK-3) signaling in primary cortical (CTX) and hippocampal (HIP) neurons prepared from rats exposed to VPA in utero. In vivo, sex-specific VPA-induced alterations in the frontal CTX transcriptome at birth were also determined. Overall, VPA induced more robust changes in neuronal function and structure in the CTX than in the HIP. Male- and female-derived primary CTX neurons from rats exposed to prenatal VPA had elevated activity and showed more disorganized firing. In the HIP, only the female VPA neurons showed elevated firing, while the male VPA neurons exhibited disorganized activity. Dendritic arborization of CTX neurons from VPA rats was less complex in both sexes, though this was more pronounced in the females. Conversely, both female and male HIP neurons from VPA rats showed elevated complexity distal to the soma. Female VPA CTX neurons also had an elevated number of dendritic spines. The relative activity of the α and β isoforms of GSK-3 were suppressed in both female and male VPA CTX neurons, with no changes in the HIP neurons. On postnatal day 0, alterations in CTX genes associated with neuropeptides (e.g., penk, pdyn) and receptors (e.g., drd1, adora2a) were seen in both sexes, though they were downregulated in females and upregulated in males. Together these findings suggest that substantial sex differences in neuronal structure and function in the VPA model may have relevance to the reported sex differences in idiopathic ASD.
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http://dx.doi.org/10.1016/j.pnpbp.2024.111222 | DOI Listing |
Prog Neuropsychopharmacol Biol Psychiatry
December 2024
Department of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, Ontario N1G 2W1, Canada. Electronic address:
There are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is based upon the human fetal valproate spectrum disorder, which is associated with increased risk of developing ASD. This model, which displays significant social, learning, and memory alterations, has therefore been widely used to further our understanding of specific biological features of ASD.
View Article and Find Full Text PDFLife Sci Alliance
February 2025
https://ror.org/01b6kha49 The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Mol Neurobiol
October 2024
Laboratory of Translational Neuroscience, Division of Neuroscience, Yenepoya Research Center, Yenepoya (Deemed to be University), University Road, Deralakatte, Mangalore, 575018, Karnataka, India.
Naringin (NAR), a flavanone glycoside, occurs widely in citrus fruits, vegetables, and alcoholic beverages. Despite evidence of the neuroprotective effects of NAR on animal models of ischemic stroke, brain cell-type-specific data about the antioxidant efficacy of NAR and possible protein targets of such beneficial effects are limited. Here, we demonstrate the brain cell type-specific prophylactic role of NAR, an FDA-listed food additive, in an in vitro oxygen-glucose deprivation (OGD) model of cerebral ischemia using MTT and DCFDA assays.
View Article and Find Full Text PDFFront Neurosci
June 2024
Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, United States.
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary Tau tangles in the brain. We previously identified a set of candidate AD microRNAs (miRNAs) in human cerebrospinal fluid (CSF) and used a target prediction pipeline to identify mRNAs and pathways that could potentially be regulated by the miRNAs. Of these pathways, clathrin mediated endocytosis (CME) was selected for further investigation.
View Article and Find Full Text PDFJ Musculoskelet Neuronal Interact
June 2024
Department of Orthopedics, Chun 'an County Hospital of Traditional Chinese Medicine, Hangzhou, China.
Objective: To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y (NPY) and prostaglandin E2 (PGE2) in elderly patients with osteoporotic lumbar vertebral compression fracture (OVCF).
Methods: The medical records of 118 elderly patients with OVCF who received treatment at our hospital from March 2018 to March 2020 were collected and analyzed retrospectively. Vertebral body height, spinal function, pain degree, and lumbar BMD were compared between the two groups upon admission and three years after the operation.
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