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Psychiatric disorders, which include a variety of distinct infirmities, affect millions of people worldwide. Without intervention, the impact of these conditions is devastating, compromising the daily life of patients and their relatives. Although insights into the underlying cortical circuitry of psychiatric diseases have emerged over the years, our understanding of their pathophysiology, elucidation of pathophysiologic mechanisms and relevant advancements in clinical therapeutic strategies have been hampered by the complexity of these neural networks and the lack of reliable biomarkers in human subjects and animal models. In this issue of , Vogt and colleagues add significant new insights to the understanding of the etiology of psychiatric conditions by revealing novel contribution of synaptic lipids to altered circuit function and behavior in mice (Vogt , 2016).
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http://dx.doi.org/10.15252/emmm.201505749 | DOI Listing |
J 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 PDFBiochem Biophys Res Commun
September 2025
Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, PR China. Electronic address:
Epidemiological studies have reported that social isolation increases the risk of diabetes, but the underlying neural mechanism remains unclear. Using a long-term single-housed (SH) mouse model of social isolation, SH mice not only exhibited disrupted glucose homeostasis, evidenced by elevated fasting glucose, impaired glucose tolerance, and reduced insulin sensitivity, but also showed hypertrophic adipocytes and altered lipid metabolism. To elucidate the neural mechanisms underlying these metabolic disturbances, retrograde trans-synaptic tracing revealed the paraventricular nucleus (PVN) and locus coeruleus (LC) as the most PRV-labeled brain regions, suggesting their potential roles in social isolation-induced hyperglycemia.
View Article and Find Full Text PDFEnviron Res
September 2025
Department of Biological Sciences, Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
Organophosphate flame retardants (OPFRs) are widely used environmental contaminants with suspected developmental neurotoxicity, yet their stage-specific molecular impacts and potential relevance to autism spectrum disorder (ASD) remain poorly defined. We integrated transcriptomic and lipidomic analyses from two rat models to investigate OPFR-induced disruption across early neurodevelopment. In dataset GSE148266, fetal forebrain and placenta were analyzed following in utero OPFR exposure; in dataset GSE211430, neonatal cortical RNA-seq and lipidomics were profiled after postnatal exposure to triphenyl phosphate and isopropylated triaryl phosphate (1,000 μg/day; n = 10/sex/group).
View Article and Find Full Text PDFCNS Neurosci Ther
September 2025
Key Laboratory of Ministry of Education for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: The apolipoprotein E (ApoE) ε4 allele and type 2 diabetes mellitus (T2DM) are independent risk factors for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in the elderly. The T2DM patients carrying the ApoE ε4 allele exhibit heightened activation of platelet glycogen synthase kinase-3β (GSK-3β), a key downstream kinase in the insulin signaling pathway, along with more severe cognitive deficits. This observation suggests an intrinsic link between ApoE ε4, GSK-3β, and cognitive dysfunction.
View Article and Find Full Text PDFACS Chem Neurosci
September 2025
Department of Neurosurgery, The Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic development and plasticity. It is a promising therapeutic target for improving neurofunctional outcomes after traumatic brain injury (TBI). However, the delivery of BDNF faces several significant challenges including limited entry into the CNS due to blood-brain barrier (BBB), short half-life, and potential side effects.
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