Neuroscience
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Neuropeptide-S (NPS) has been demonstrated to mitigate learning and memory deficits in experimental models of Parkinson's Disease (PD). Despite this, the precise mechanisms through which NPS exerts its influence on cognitive functions remain to be fully unknown. This study aims to elucidate the effects of central administration of NPS on learning and memory deficits associated with an experimental rat hemiparkinsonian model, examining both electrophysiological and molecular parameters. ⋯ In 6-OHDA-lesioned rats, NPS treatment significantly (p < 0.05) enhanced the amplitude of LTP at the dentate gyrus/perforant path synapses. Furthermore, NPS significantly (p < 0.05) increased the number of pCaMKII and GluR1 immunoreactive cells in the hippocampus, which had been diminished due to 6-OHDA, except for GluR2 levels. These findings provide insight into the mechanisms by which central NPS administration enhances cognitive functions in an experimental model of PD, highlighting its potential therapeutic benefits for addressing cognitive deficits in PD.
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Exercise-induced fatigue (EF) is characterized by a decline in maximal voluntary muscle force following prolonged physical activity, influenced by both peripheral and central factors. Central fatigue involves complex interactions within the central nervous system (CNS), where astrocytes play a crucial role. This study explores the impact of astrocytic calcium signals on EF. ⋯ Utilizing genetic tools to either enhance or reduce astrocytic calcium signaling, we observed corresponding decreases and increases in exercise-induced fatigue time, respectively. Furthermore, modulation of astrocytic calcium signals influenced corticostriatal synaptic plasticity, with increased signals impairing and decreased signals ameliorating long-term depression (LTD). These results highlight the pivotal role of astrocytic calcium signaling in the regulation of exercise-induced fatigue and synaptic plasticity in the striatum.
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Early life stress (ELS) is thought to be a leading cause of mental disorders in adulthood, including PTSD. Recent studies have found that such stress has a gender and resilient specific effect on adult PTSD. This study aimed to assess emotion, and cognitive behavior, and to examine the sex differences and resilience of ELS on adult PTSD. ⋯ The SPS effect and MS*SPS interaction significantly impacted TRF1 and TRF2 protein expression. In conclusion, this study shows that MS has different effects on anxiety, depression, and cognitive memory deficits in rats experiencing "secondary stress" in adulthood and is accompanied by telomere shortening in the hippocampus. This reveals the potential impact of early MS on PTSD and provides a new perspective for further research in the field of psychological stress.
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Intestinal immunity is associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes. Recent evidence also suggests its implication in the pathogenesis of autoimmune diseases affecting the central nervous system, such as multiple sclerosis (MS). However, there is ongoing debate regarding which part of the intestinal tract contributes to the development of MS. ⋯ Additionally, we highlighted an increase in dendritic cells and monocytes/macrophages in the colonic lamina propria of EAE animals during the presymptomatic phase. Altogether, our findings indicate that both small intestine and colon are involved in the pathogenesis of EAE, despite engaging distinct immunological processes. This study provides new insights for understanding the roles of intestinal lymphoid and myeloid immune cells on the pathogenesis of MS and other autoimmune diseases.
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Previously, we reported that both S-nitrosoglutathione (GSNO), a carrier of cellular nitric oxide, and N6022, an injectable form of GSNO reductase (GSNOR) inhibitor that increases endogenous GSNO levels, alleviate experimental autoimmune encephalomyelitis (EAE) in mice by suppressing Th1 and Th17 immune responses. Building on these findings, we explored the role of GSNOR in EAE pathogenesis and evaluated the efficacy of an orally active GSNOR inhibitor (N91115) in treating the EAE disease. EAE mice exhibited heightened expression/activity of GSNOR in the spinal cord, and the knockout of the GSNOR gene resulted in much milder clinical manifestations of EAE, with lower degrees of demyelination and axonal loss, reduced microglial and astrocyte activations, as well as suppressed Th1 and Th17 cell responses, alongside bolstered Treg immune responses. ⋯ This observation underscores the potential of increased GSNOR expression and activity as a risk factor exacerbating EAE immunopathology, while simultaneously highlighting its potential as a target for modifying the disease. Furthermore, the balanced immune regulation provided by orally active N91115 (IL-6/IL-17a vs. IL-10) presents a promising alternative to immunosuppressive drugs, reducing the risk of opportunistic infections.