Neuroscience
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Exercise has been reported to elicit a transient suppression of appetite. Plasma lactate, which is produced by exercising muscle, is believed to have a critical effect on exercise-induced appetite suppression. However, the underlying mechanisms and signaling steps of central lactate metabolism remain unexplored. ⋯ Moreover, acute exercise led to an increase in the phosphorylation of Jak2 and STAT3 in the hypothalamus, while central lactate inhibition significantly blunted this effect. In addition, HIF-1α expression increased obviously after exercise, while it was attenuated by central oxamate administration. Collectively, our data reveal that central lactate metabolism mediates exercise-induced suppression of appetite and changes in neuropeptides, possibly through enhanced Jak2-STAT3 signaling.
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Alpha-synuclein induced degeneration of the midbrain substantia nigra pars compact (SNc) dopaminergic neurons causes Parkinson's disease (PD). Rodent studies demonstrate that nigrostriatal dopamine stimulates pallidal neurons which, via the topographical pallidocortical pathway, regulate cortical activity and functions. We hypothesize that nigrostriatal dopamine acting at the basal ganglia regulates cortical activity in sleep and wake state, and its depletion systemically alters electroencephalogram (EEG) across frequencies during sleep-wake state. ⋯ ML algorithms construct a model based on empirical data to make predictions on subsequent data. The accuracy of the predictive results indicate that nigrostriatal dopamine depletion increases global EEG spectral synchronization in wake, NREM sleep, and REM sleep. The EEG changes can be exploited by ML to identify SNc lesions at a high accuracy.
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The sigma-1 and sigma-2 (σ1 and σ2) receptors are found in high concentrations in the brain, and their altered expression leads to a variety of neuropsychiatric disorders. 3-di-tolylguanidine (DTG) stimulates the activity of both of these receptors. We assessed the effects of administering DTG to adult male Sprague Dawley rats on learning and memory consolidation processes and on the levels of neurotransmitters in selected brain structures. Spatial learning and memory were evaluated in the water maze test. ⋯ Since the administration of DTG led to differences in dopaminergic transmission, it was assumed to influence memory processes in this way. Changes in histidine, serine, alanine, taurine, and glutamic acid levels in selected structures of the brains of rats with memory impairment were also observed. We conclude that long-term administration of DTG modulates spatial learning and memory in rats and changes the concentrations of neurotransmitters in the hippocampus, prefrontal cortex, and striatum..
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PR-957 [low molecular mass polypeptide (LMP)-7 selective inhibitor] regulates T helper (Th) cell differentiation and inflammatory response in multiple neurological diseases. Hence, this study aimed to explore the effect of PR-957 on Th1/Th2/Th17 cell differentiation, therapeutic efficacy and its potential mechanisms in Alzheimer's disease (AD). The LMP7 expressions in peripheral blood mononuclear cells from 30 AD patients and 30 healthy controls (HC) were detected. ⋯ SC79 addition upregulated pAKT/AKT expression, Th1 cells, and Th17 cells, while downregulated Th2 cells; also SC79 could alleviate the effect of PR-957 on regulating PI3K/AKT pathway and Th1, Th2, and Th17 cell differentiation in AD CD4+ T cells. Furthermore, PR-957 attenuated cognitive impairment and neurofibrillary tangle; also it inhibited Th17 cell differentiation and PI3K/AKT pathway in the brain and spleen of AD mice. In conclusion, PR-957 suppresses Th1 and Th17 cell differentiation, attenuates neural injury and improves cognitive function via inactivating PI3K/AKT pathway in AD.