Neuroscience
-
Neuronal apoptosis plays important roles in the early brain injury after subarachnoid hemorrhage (SAH). This study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood-brain-barrier (BBB) disruption after SAH. We chose apelin-13, ATF6 and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) siRNAs to verify the hypothesis. ⋯ What's more, the administration of apelin-13 could reduce brain edema, ameliorate BBB disruption and improve neurological functions. However, the CHOP siRNA could significantly reverse the pro-apoptotic effect induced by the increased ATF6 level after SAH. Apelin-13 could exert its neuroprotective effects via suppression of ATF6/CHOP arm of ER-stress-response pathway in the early brain injury after SAH.
-
Painful neuropathic injuries are accompanied by robust inflammatory and oxidative stress responses that contribute to the development and maintenance of pain. After neural trauma the inflammatory enzyme cyclooxygenase-2 (COX-2) increases concurrent with pain onset. Although pre-treatment with the COX-2 inhibitor, meloxicam, before a painful nerve root compression prevents the development of pain, the pathophysiological mechanisms are unknown. ⋯ Oxidative damage following nerve root compression was found predominantly in neurons rather than glial cells. The expression of 8-OHG in DRG neurons at day 7 was reduced with meloxicam. These findings suggest that meloxicam may prevent the onset of pain following nerve root compression by suppressing inflammation and oxidative stress both centrally in the spinal cord and peripherally in the DRG.
-
Whereas environmental challenges during gestation have been repeatedly shown to alter offspring brain architecture and behavior, exploration examining the consequences of paternal preconception experience on offspring outcome is limited. The goal of this study was to examine the effects of preconception paternal stress (PPS) on cerebral plasticity and behavior in the offspring. Several behavioral assays were performed on offspring between postnatal days 33 (P33) and 101 (P101). ⋯ Neuroanatomical measures revealed a heavier brain in stressed animals and dendritic changes in all regions measured, the precise effect varying with the measure and cerebral region. Thus, PPS impacted both behavior and neuronal morphology of offspring. These effects likely have an epigenetic basis given that in a parallel study of littermates of the current animals we found extensive epigenetic changes at P21.
-
The brain is capable of improving from a chronically stressed state. The hippocampus in particular appears to "recover" from chronic stress-induced morphological and functional deficits following a post-stress rest period of several weeks. We previously found that hippocampal brain-derived neurotrophic factor (BDNF) was necessary for spatial ability to improve following a post-stress rest period. ⋯ In the second study, we tested whether the TrkB receptor was involved by administering daily systemic injections of ANA-12, a TrkB receptor antagonist, during the three-week post-stress rest period. ANA-12 prevented the improvement in spatial ability and CA3 apical dendritic complexity following the post-stress rest period. These data demonstrate that hippocampal BDNF acting via its TrkB receptor is necessary during the post-stress rest period in order to improve the impaired hippocampal structural and cognitive outcomes that occur in response to chronic stress.
-
The purpose of this study was to determine the response, in rat, to chronic physical activity in small and large DRG neurons. Rats were cage-confined or underwent 16-18 weeks of daily increased activity, via 2 h of treadmill running per day or free access to voluntary exercise wheels, following which small (≤30 µm) and large (≥40 µm) diameter DRG neurons were harvested by laser capture microdissection from flash-frozen lumbar DRGs. Relative mRNA levels were determined using real-time polymerase chain reaction. ⋯ In large DRG neurons, voluntary wheel exercise decreased the expression for 5HT1D receptors, whereas both treadmill and voluntary wheel exercise decreased the expression of mRNA for TrkC receptors. DRG neurons show slightly more changes in gene expression after voluntary exercise compared to the treadmill exercise group. Small and large lumbar sensory neurons are responsive to chronically increased neuromuscular activity by changing the expression of genes, the products of which could potentially change the sensory processing of nociceptors and proprioceptors, which could in turn alter functions such as pain transmission and locomotor coordination.