Neuroscience
-
This study investigated the mechanisms underlying regulation of the serotonin system in the rat brain during exercise-induced chronic fatigue. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed to measure serum tryptophan of the fatigued rat. HPLC was conducted to measure 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex and hippocampus. ⋯ Further, 5-HTT expression was significantly increased and 5-HT1A receptor expression was significantly decreased. These results indicate that the 5-HT system plays an important role in the development of exercise-induced chronic fatigue. The 5-HT levels in different parts of the brain increased simultaneously, especially at synapses, and these alterations were associated with changes in 5-HTT and 5-HT1A mRNA expressions.
-
The metabolic pathophysiology underlying ischemic stroke remains poorly understood. To gain insight into these mechanisms, we performed a comparative metabolic and transcriptional analysis of the effects of cerebral ischemia on the metabolism of the cerebral cortex using middle cerebral artery occlusion (MCAO) rat model. Metabolic profiling by gas-chromatography/mass-spectrometry analysis showed clear separation between the ischemia and control group. ⋯ Furthermore, intracerebroventricular injection of ataxia telangiectasia mutated (ATM) kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD upregulation after MCAO, but that of protein kinase D inhibitor (CID755673) did not affect HSP27 phosphorylation. Consequently, G6PD activation via ischemia-induced HSP27 phosphorylation by ATM kinase may be part of an endogenous antioxidant defense neuroprotection mechanism during the earliest stages of ischemia. These findings have important therapeutic implications for the treatment of stroke.
-
Neuropathic pain is absent in infants and emergent years after injury. Adult spinal cord microglia play a key role in initiating neuropathic pain, and modulation of microglia is a potential target for treating neuropathic pain. In this study, we evaluated the role of microglia after infant peripheral nerve injury and the effect of exercise on the delayed-onset neuropathic pain. ⋯ Exercise shifted spinal cord microglia polarization to the M2 phenotype and reduced neuropathic pain. In addition, IL-10 increased and TNF-α decreased after exercise, and intrathecal injection of the IL-10 antibody reduced the exercise-induced analgesia. Our study found that infant nerve injury induced delayed spinal cord microglia polarization to the M1 phenotype and that exercise was effective in the treatment of delayed adolescent neuropathic pain via the modulation of microglial polarization.
-
Altered corneal reflex activity is a common feature of dry eye disease (DE). Trigeminal sensory nerves supply the ocular surface and terminate at the trigeminal interpolaris/caudalis (ViVc) transition and spinomedullary (VcC1) regions. Although both regions contribute to corneal reflexes, their role under dry eye conditions is not well defined. ⋯ Blockade of N-methyl-D-aspartate (NMDA) receptors at either region reduced HS-evoked OOemgL activity in DE and sham rats. GABAαβ3 receptor density was reduced at the ViVc transition, while NMDA receptor density was increased at both regions in DE rats. Loss of GABAergic inhibition at the ViVc transition coupled with enhanced NMDA excitatory amino acid neurotransmission at the ViVc transition and the VcC1 region likely contribute to altered corneal reflexes under dry eye conditions.
-
Fragile X mental retardation protein (FMRP), an important RNA-binding protein responsible for fragile X syndrome, is involved in posttranscriptional control of gene expression that links with brain development and synaptic functions. Here, we reveal a novel role of FMRP in pre-mRNA alternative splicing, a general event of posttranscriptional regulation. Using co-immunoprecipitation and immunofluorescence assays, we identified that FMRP interacts with an alternative-splicing-associated protein RNA-binding protein 14 (RBM14) in a RNA-dependent fashion, and the two proteins partially colocalize in the nuclei of hippocampal neurons. ⋯ RNA immunoprecipitation assays indicate that FMRP promotes RBM14's binding to the mRNA targets. In addition, overexpression of the long form of Protrudin or the short form of Tau promotes protrusion growth of the retinoic acid-treated, neuronal-differentiated Neuro-2a cells. Together, these data suggest a novel function of FMRP in the regulation of pre-mRNA alternative splicing through RBM14 that may be associated with normal brain function and FMRP-related neurological disorders.