Brain research
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We investigated in different experimental rat models the potential facilitatory contribution of the medullary dorsal reticular nucleus (DRt) descending pathway to the expressions of the sensory spinal neuron sensitization such as increased spontaneous and noxious evoked activities, responsivity to heterotopic afferences stimulation and long lasting afterdischarges (ADs). We carried out experiments by recording from ipsilateral lumbar Wide Dynamic Range (WDR) neurons and by simultaneously monitoring the DRt neuron activity in neuropathic pain rats with chronic constriction injury of one sciatic nerve (CCI), in sham-operated and in "intact" rats. In particular, we recorded the spinal neuron spontaneous activities and the activities evoked by noxious stimulations of ipsi- and contralateral sciatic supplied areas before and during DRt activity blockade. ⋯ We found that during DRt activity blockade in CCI rat neurons and in "intact" rat NMDA-treated neurons, the spontaneous activity was significantly reduced, the responses to contralateral sciatic area stimulation were reduced or suppressed, the responses to ipsilateral sciatic area were poorly affected (slightly reduced or unaffected), except for the poststimulus afterdischarges that were mostly suppressed. In sham-operated rats, the neuronal activity was not affected by DRt blockade. The finding that during the DRt nucleus blockade some expressions of spinal neurons sensitization, seemingly associated to sensory disorders in neuropathic pain, fade or extinguish designates a likely facilitatory role of DRt in the maintenance of neuronal sensitization and thus a contribution to neuropathic pain state.
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There is compelling evidence indicating that reduction of high-density lipoprotein (HDL) level is associated with increased risk of Alzheimer's disease (AD). It is known that the levels of HDL are regulated by cholesteryl ester transfer protein (CETP) and several single nucleotide polymorphisms (SNPs) in the CETP gene have been shown to be associated with the levels of HDL. Therefore, it is assumed that the CETP gene is a reasonable candidate for modifying the susceptibility in AD. ⋯ When the sample was stratified by APOE epsilon4 carrier status, the same tendency (P=0.042 for DG genotype, P=0.046 for G allele) was observed in the presence of APOE epsilon4, but not in the absence of APOE epsilon4 (P=0.284 for DG genotype, P=0.298 for G allele). However, these results became not statistically significant after correcting for multiple testing (Bonferroni) because of limited number of our sample. Our current results suggest that G allele of CETP D442G may have a potential protective effect against the development of AD, especially in APOE epsilon4 carriers, in Northern Han-Chinese, possibly through regulating the HDL level in the brain.
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We examined calcitonin gene-related peptide (CGRP) expression dynamics in the dorsal root ganglia (DRGs) and spinal cords of adult rats subjected to one of the following three types of unilateral sciatic nerve injury: crush (SNC), ligation (SNL), or transection combined with subsequent neurorrhaphy (SNT). Following SNC, CGRP immunoreactivity (IR) was increased in ipsilateral primary sensory neurons of L4-L5 DRGs, laminae I-II and spinal motoneurons; an area of CGRP-labeled fibers in ipsilateral laminae III-V was also increased in size following SNC. CGRP up-regulation exhibited a distinct temporospatial pattern and expression levels had returned to baseline levels by the end of the 28-day test period. ⋯ Interestingly, SNL did not affect CGRP-IR in spinal motoneurons, but did result in an accumulation of nerve growth factor (NGF) distal to ligature that was apparent as early as 1 day post-injury and persisted throughout the experimental period. These findings indicate that the nature of peripheral nerve injury has an impact on CGRP expression dynamics and that the response involves target tissues in vivo. Our results have important implications for elucidating the mechanisms of nerve regeneration.