Neuroscience
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Schizophrenia, a complex psychiatric disorder with diverse symptoms, has been linked to ketamine, known for its N-methyl-D-aspartate (NMDA) receptor antagonistic properties. Understanding the distinct roles and mechanisms of ketamine is crucial, especially regarding its induction of schizophrenia-like symptoms. Recent research highlights the impact of ketamine on key brain regions associated with schizophrenia, specifically the prefrontal cortex (PFC) and hippocampus (Hip). ⋯ In the Hip, 129 differentially expressed proteins were screened, mainly related to synaptic plasticity proteins and mitochondrial respiratory chain complex-associated proteins. Additionally, we investigated key proteins within the glutamatergic synapse pathway and observed decreased expression levels of phosphorylated CaMKII and CREB. Overall, the study unveiled a significant proteomic signature in the chronic ketamine-induced schizophrenia mouse model, characterized by anxiety and cognitive impairment in both the PFC and Hip, and this comprehensive proteomic dataset may not only enhance our understanding of the molecular mechanisms underlying ketamine-related mental disorders but also offer valuable insights for future disease treatments.
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Corticosteroids are commonly used in the treatment of inflammatory low back pain, and their nominal target is the glucocorticoid receptor (GR) to relieve inflammation. They can also have similar potency at the mineralocorticoid receptor (MR). The MR has been shown to be widespread in rodent and human dorsal root ganglia (DRG) neurons and non-neuronal cells, and when MR antagonists are administered during a variety of inflammatory pain models in rats, pain measures are reduced. ⋯ MR KO unmyelinated C neurons are more excitable under normal and inflamed conditions, while MR KO does not affect excitability of myelinated A cells. MR KO in sensory neurons causes a reduction in overall GR mRNA but is protective against reduction of the anti-inflammatory GRα isoform during LID. These effects of MR KO in sensory neurons expanded our understanding of MR's functional role in different neuronal subtypes (A and C neurons), and its interactions with the GR.
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When a musician practices a new song, hitting a correct note sounds pleasant while striking an incorrect note sounds unpleasant. Such reward and punishment feedback has been shown to differentially influence the ability to learn a new motor skill. Recent work has suggested that punishment leads to greater movement variability, which causes greater exploration and faster learning. ⋯ In Experiment 2, we again found that punishment led to significantly less movement variability compared to reward (n = 34). Collectively our results suggest that punishment feedback leads to less movement variability. Future work should investigate whether punishment feedback leads to a greater knowledge of movement variability and or increases the sensitivity of updating motor actions.
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Mitochondrial dysfunction, which results in the overproduction of oxygen free radicals, is a crucial mechanism underlying cerebral ischemia-reperfusion injury. 4'-Hydroxyl-2-substituted phenylnitronyl nitroxide (HPN), which is an antioxidant and free radical scavenger, can effectively scavenge oxygen free radicals, suggesting its potential as a protective agent against cerebral ischemia-reperfusion injury. In this study, we investigated the effects of HPN on mitochondrial function and apoptosis following cerebral ischemia/reperfusion injury in rats. Healthy adult SD rats were chosen as the experimental subjects, and the rat ischemia/reperfusion injury model was generated using the modified Zea Longa method. ⋯ Additionally, HPN effectively preserved the morphology and function of mitochondria, reduced the protein and gene expression of Caspase-3 and Bax, increased the protein and gene expression of Bcl-2, mitigated neuronal apoptosis, improved neurological deficits, and decreased the volume of cerebral infarction. Of interest, the protective effect on brain tissue was more evident with increasing doses of HPN. These findings indicate that HPN can serve as an effective protective agent against cerebral ischemia-reperfusion injury.
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Limb immobilization is known to cause significant decreases in muscle strength and muscle mass as early as two days following the onset of immobilization. However, the decline in strength surpasses the decline in muscle mass, suggesting that factors in addition to muscle loss, such as neuroplasticity, contribute to the decrease in force production. However, little is known regarding immobilization-induced neural changes, although sensorimotor regions seem to be the most affected. ⋯ The results showed changes predominantly involving cerebellar connectivity. For example, the immobilization period caused a decrease in connectivity between the motor cerebellar region of the immobilized arm and the left temporal lobe, and an increase between the same cerebellar region and the supplementary motor area. Overall, changes in connectivity occurred in regions typically associated with error detection and motor learning, suggesting a potential functional reorganization of the brain within 14 days of elbow immobilization.