Neuroscience
-
Comparative Study
Increased expression of Ca2+/calmodulin-dependent protein kinase II alpha during chronic morphine exposure.
The chronic administration of morphine and related opioid drugs results in tolerance and dependence which limits the clinical utility of these agents. Neuronal plasticity is probably responsible in large part for tolerance and dependence. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in the neuroplastic events underlying memory formation and other phenomena. ⋯ In addition, the abundance of phosphorylated CaMKIIalpha was increased in spinal cord tissue from morphine-treated mice. We conclude that enhanced CaMKIIalpha expression and activity in spinal cord tissue may contribute to the development of morphine tolerance in mice. The involvement of this enzyme in opioid tolerance suggests other parallels may exist between the neuroplastic events related to memory formation and those related to opioid tolerance or pain.
-
The novelty of a cue may arise from the presence of an element that has not previously been experienced or from familiar elements that have been rearranged. The present study mapped the anatomical basis of responding to this second form of novelty. For this, rats were trained on a working memory spatial task in a radial-arm maze in a cue-controlled environment. ⋯ In contrast, no changes were observed in other sites including the perirhinal cortex, postrhinal cortex, lateral and medial entorhinal cortices, retrosplenial cortices, or anterior thalamic nuclei. These results highlight the selective involvement of the hippocampus for processing novel rearrangements of visual stimuli and suggest that this involvement is intrinsic as it is independent of the parahippocampal cortices. This pattern of Fos changes is the mirror image of that repeatedly found for novel individual stimuli (perirhinal increase, no hippocampal change), demonstrating that these two forms of novelty have qualitatively different neural attributes.
-
Exercise is increasingly recognized as an intervention that can reduce CNS dysfunctions such as cognitive decline, depression and stress. Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) is increased in the hippocampus following exercise. In this study we tested the hypothesis that exercise can counteract a reduction in hippocampal BDNF protein caused by acute immobilization stress. ⋯ This study demonstrates that CORT modulates stress-related alterations in BDNF protein. Further, exercise can override the negative effects of stress and high levels of CORT on BDNF protein. Voluntary physical activity may, therefore, represent a simple non-pharmacological tool for the maintenance of neurotrophin levels in the brain.
-
Gap junctions between glial cells in mammalian CNS are known to contain several connexins (Cx), including Cx26, Cx30 and Cx43 at astrocyte-to-astrocyte junctions, and Cx29 and Cx32 on the oligodendrocyte side of astrocyte-to-oligodendrocyte junctions. Recent reports indicating that oligodendrocytes also express Cx47 prompted the present studies of Cx47 localization and relationships to other glial connexins in mouse CNS. In view of the increasing number of connexins reported to interact directly with the scaffolding protein zonula occludens-1 (ZO-1), we investigated ZO-1 expression and Cx47/ZO-1 interaction capabilities in brain, spinal cord and Cx47-transfected HeLa cells. ⋯ ZO-1 was found to co-immunoprecipitate with Cx47, and pull-down assays indicated binding of Cx47 to the second PDZ domain of ZO-1. Our results indicate widespread expression of Cx47 by oligodendrocytes, but with a distribution pattern in relative levels inverse to the abundance of Cx29 in myelin and paucity of Cx29 in oligodendrocyte somata. Further, our findings suggest a scaffolding and/or regulatory role of ZO-1 at the oligodendrocyte side of astrocyte-to-oligodendrocyte gap junctions.
-
Comparative Study
Cocaine- and amphetamine-regulated transcript peptide (CART) is a selective marker of rat granule cells and of human mossy cells in the hippocampal dentate gyrus.
Cocaine- and amphetamine-regulated transcript (CART) peptide immunocytochemistry was used to reveal cellular localization in the dentate gyrus and in Ammon's horn of the rat and human hippocampal formations. In the rat dentate gyrus, only granule cells were labeled, whereas in humans, only mossy cells of the hilar region expressed CART peptide immunoreactivity. In the rat, CART-positive granule cells were located at the molecular layer border of the granule cell layer and had no features that would distinguish them from other granule cells. ⋯ The specific location of CART peptide in the dentate granule cells of rodents and in the mossy cells of the human hippocampus may indicate involvement of neuronal circuitry of the dentate gyrus in the memory-related effects of cocaine and amphetamine. Independently of its functional role, CART peptide can be used as a specific marker of human mossy cells and of the dentate associational pathway. The sensitivity of CART peptide to postmortem autolysis may restrict the use of this marker in surgically removed hippocampi or in human brains removed and fixed shortly after death.