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Autism Spectrum Disorders (ASD) are the second most common developmental cause of disability in the United States. ASDs are accompanied with substantial economic and emotional cost. The brains of ASD patients have marked structural abnormalities, in the form of increased dendritic spines and decreased long distance connections. These structural differences may be due to deficiencies in Heparin Sulfate (HS), a proteoglycan involved in a variety of neurodevelopmental processes. Of particular interest is its role in the Slit/Robo pathway. The Slit/Robo pathway is known to be involved in the regulation of axonal guidance and dendritic spine formation. HS mediates the Slit/Robo interaction; without its presence Slit's repulsive activity is abrogated. Slit/Robo regulates dendritic spine formation through its interaction with srGAPs (slit-robo GTPase Activating Proteins), which leads to downstream signaling, actin cytoskeleton depolymerization and dendritic spine collapse. Through interference with this pathway, HS deficiency can lead to excess spine formation.
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http://dx.doi.org/10.1186/s13064-016-0066-x | DOI Listing |
Mol Psychiatry
September 2025
Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, 44115, USA.
Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.
View Article and Find Full Text PDFJ Vis Exp
August 2025
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University;
Examining circadian synaptic plasticity requires housing mice under different lighting conditions (light/dark cycle, LD 12:12, and constant darkness, DD), providing access to running wheels, and sacrificing them at four defined time points within 24 h-at the beginning and middle of the day/subjective day and at the beginning and middle of the night/subjective night. Brains are then properly fixed for transmission electron microscopy (TEM). The barrel cortex, with its precise somatotopic organization, provides an ideal model for such analysis.
View Article and Find Full Text PDFJ Cell Biol
November 2025
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Two major protein recycling pathways have emerged as key regulators of enduring forms of synaptic plasticity, such as long-term potentiation (LTP), yet how these pathways are recruited during plasticity is unknown. Phosphatidylinositol-3-phosphate (PI(3)P) is a key regulator of endosomal trafficking and alterations in this lipid have been linked to neurodegeneration. Here, using primary hippocampal neurons, we demonstrate dynamic PI(3)P synthesis during chemical induction of LTP (cLTP), which drives coordinate recruitment of the SNX17-Retriever and SNX27-Retromer pathways to endosomes and synaptic sites.
View Article and Find Full Text PDFRev Esp Anestesiol Reanim (Engl Ed)
September 2025
Department of Neurology, Xuzhou Central Hospital, Xuzhou, China. Electronic address:
Objective: This study aims to investigate the effects of anaesthesia and surgical procedures on the cognitive function of both young and aged mice. It will also explore the role and mechanisms of c-Fos expression in altering hippocampal neuron excitability and its relationship with perioperative neurocognitive disorders in mice.
Methods: In this study, we used a murine laparotomy model to assess cognitive behavioural changes in both young and aged mice at 1, 3, and 7 days post-surgery.
Adv Sci (Weinh)
September 2025
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Institute of Anesthesiology, Tianjin, 300052, China.
Sevoflurane-induced neurotoxicity is age-dependent, but the role of sex differences is unclear. While testosterone has protective effects, the impact of estrogen remains unknown. This study investigates the effects of sevoflurane on neurotoxicity in adult, middle-aged, and aged male and female mice.
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