2026-06-30 | High-Fat Diet Exacerbates Neuropathology in a Transgenic Mouse Model of Multiple System Atrophy.

Multiple system atrophy (MSA) is a rare and devastating neurodegenerative disorder. Accumulating clinical and preclinical evidence suggests that diabetes and insulin resistance may adversely influence MSA pathophysiology. We investigated the potential association between diabetes, impaired glucose homeostasis, and MSA neuropathology in rodents. We subjected the PLP-SYN (proteolipid promoter) transgenic mouse model of MSA to either a standard chow diet or a high-fat diet (HFD) for 4 months to induce diet-associated metabolic alterations. Metabolic, neuropathological, and behavioral parameters were subsequently evaluated at multiple time points. PLP-SYN mice fed a HFD exhibited a more pronounced diabetic phenotype, characterized by aggravated peripheral glucose dysregulation and insulin resistance, compared with wild-type mice on the same diet. Moreover, 4 months of HFD feeding aggravated MSA-related neuropathology, as evidenced by increased α-synuclein accumulation and enhanced dopaminergic neurodegeneration, accompanied by accelerated impairment of fine motor function. Collectively, these findings indicate an association between dysregulated glucose metabolism and MSA neuropathology. Our results further support the potential of modulating glucose metabolism to slow disease progression in MSA and provide additional rationale for exploring whether antidiabetic agents could provide therapeutic benefits. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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2026-06-26 | Effects of Environmental Arsenic Exposure on the Morphology of Multiple Organs in Female Mice During Pre-Pregnancy, Gestation, and Lactation.

To investigate the effects of environmentally relevant arsenic (As) exposure on multiple organs (liver, kidney, spleen, ovary, and uterus) in female mice during pre-pregnancy, gestation, and lactation, and to clarify the critical time window associated with As-induced organ toxicity. As exposure models (0.02, 0.1, or 0.5 mg/L As2O3) were established for mice during pre-pregnancy, gestation, and lactation. Meanwhile, the effects on the fertility of female mice, blood parameters, and pathological changes of the liver, kidneys, spleen, ovaries and uterus of the exposed mice were evaluated. Additionally, a marker of DNA-strand break (γH2AX) and apoptosis (TUNEL) was assessed in the liver and kidney during gestation and lactation. The findings indicated that As exposure during these stages did not impair fertility in female mice. However, exposure to 0.5 mg/L As2O3 during gestation caused reductions in red blood cells (RBC), hemoglobins (HGB), and platelets (PLT). Meanwhile, hepatic lipid levels was increased in mice exposure to 0.1 mg/L As2O3 during gestation, and mice exposed to 0.1 mg/L As2O3 during lactation exhibited glomerular atrophy and hepatocyte vacuolization. In addition, mice exposed to 0.5 mg/L As2O3 during both gestation and lactation exhibited varying degrees of inflammatory cell infiltration in both the liver and kidney. Notably, γH2AX was elevated in the kidneys at 0.1 and 0.5 mg/L As2O3 during gestation and lactation, whereas no change was observed in the liver. TUNEL staining revealed no obvious alterations in either organ throughout this period. These observations suggest that females may be more vulnerable to As during gestation and lactation, with the liver and kidney serving as primary sites of toxicity accumulation.

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2026-06-22 | Glucagon-like peptide-1 receptor agonists in movement disorders: From Parkinson's disease to the broader spectrum - Mechanisms, evidence, and future directions.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have emerged as potential neuroprotective agents in neurodegenerative disorders. GLP-1 signaling modulates key pathogenic pathways relevant to movement disorders, including neuroinflammation, mitochondrial dysfunction, oxidative stress, and impaired proteostasis, with receptors widely expressed in motor-related brain regions. This narrative reviewaimed to summarize current mechanistic, preclinical, and clinical evidence regarding the role of GLP-1RAs across the spectrum of movement disorders. A narrative review of the literature was conducted, including preclinical studies, randomized clinical trials, observational data, and pharmacovigilance analyses evaluating GLP-1RAs in movement disorders. Preclinical studies consistently demonstrate neuroprotective effects of GLP-1RAs, including preservation of dopaminergic neurons, reduction of α-synuclein aggregation, and improvement in motor function. Clinical evidence is most advanced in Parkinson's disease, where early randomized trials of exenatide and lixisenatide suggested modest motor benefits and possible disease-modifying effects. However, subsequent larger studies, including the phase III Exenatide-PD3 trial, failed to demonstrate significant clinical benefit. Preliminary signals have been reported in multiple system atrophy, whereas evidence in Huntington's disease, essential tremor, and other movement disorders remains largely preclinical. GLP-1RAs represents a biologically plausible but as yet unproven disease-modifying strategy in movement disorders. Translational challenges, including pharmacologic heterogeneity, variability in central nervous system exposure, and clinical trial design limitations-must be addressed. Future research should focus on biomarker-guided patient selection, optimized CNS-penetrant agents, and rigorously designed clinical trials.

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