Neuroscience
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GABAergic interneurons play central roles in the regulation of neuronal activity in the basolateral nucleus of the amygdala (BLA). They are also suggested to be the principal targets of the brainstem noradrenergic afferents which are involved in the enhancement of the BLA-related memory. In addition, behavioral stress has been shown to impair noradrenergic facilitation of GABAergic transmission. ⋯ Two ionic mechanisms were involved in this excitability: the activation of nonselective cationic conductance and the suppression of the resting K+ conductance. NA also increased the frequency of spontaneous IPSCs in the principal cells of the BLA. It is suggested that the NA-dependent excitation of type-A cells attenuates the BLA output for a certain period.
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Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder in which motor neurons may be targeted by oxidative and nitrergic stress without sufficient compensation by intrinsic support mechanisms. In this work, we addressed two key tenets of this hypothesis for the pathogenesis of ALS. Using superoxide dismutase (SOD) 1G93A mice, we studied the impact of reduction of nitrergic stress within the CNS with the use of a broad spectrum nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester. ⋯ This intensive evaluation enhanced our knowledge of the time course in SOD1G93A mice and impact of the SOD1G93A mutation upon motor neurons and their function. Neither intervention had even minimal impact upon slowing progression of disease in SOD1G93A mice. Our data argue against significant roles for nitrergic stress in promoting motor neuron loss and the importance of alternative neurotrophic support mechanisms that might support motor neurons and prevent disease progression in SOD1G93A mice.
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Elevated nitric oxide (NO) and proton levels in synovial fluid are implicated in joint pathology. However, signaling pathways stimulated by these molecules that mediate inflammation and pain in the temporomandibular joint (TMJ) have not been investigated. The goal of this study was to determine the effect of NO-proton stimulation of rat trigeminal neurons on the in vivo expression of mitogen-activated protein kinases (MAPKs) and phosphatases (MKPs) in trigeminal ganglion neurons and satellite glial cells. ⋯ Increased active ERK and p38 levels as well as elevated MKP levels were also detected in neurons and satellite glial cells located in V2 and V1 regions of the ganglion. Our data provide evidence that NO-proton stimulation of V3 neurons results in temporal and spatial changes in expression of active ERK and p38 and MKPs in all regions of the ganglion. We propose that in trigeminal ganglia these cellular events, which are involved in peripheral sensitization as well as control of inflammatory and nociceptive responses, may play a role in TMJ pathology.
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Humans exposed prenatally to ethanol can exhibit brain abnormalities and cognitive impairment similar to those seen in patients expressing mutant forms of the L1 cell adhesion molecule (L1CAM). The resemblance suggests that L1CAM may be a target for ethanol, and consistent with this idea, ethanol can inhibit L1CAM adhesion in cell lines and L1CAM-mediated outgrowth and signaling in cerebellar granule neurons. ⋯ We find that ethanol does not alter axonal polarization, L1CAM-dependent axon outgrowth or branching, or L1CAM recycling in axonal growth cones. Thus, ethanol inhibition of L1CAM is highly dependent on neuronal context.
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At the optic chiasm retinal fibers either cross the midline, or remain uncrossed. Here we trace hemispheric pathways through the marmoset chiasm and show that fibers from the lateral optic nerve pass directly toward the ipsilateral optic tract without any significant change in fiber order and without approaching the midline, while those from medial regions of the nerve decussate directly. Anterograde labeling from one eye shows that the two hemispheric pathways remain segregated through the proximal nerve and chiasm with the uncrossed confined laterally. ⋯ Recently it has been shown that this distinction is not a true dichotomy between placental mammals and marsupials, as fiber order in tree shrews and humans mirrors the marsupial pattern. Architectural differences in the mature chiasm probably reflect different developmental mechanisms regulating pathway choice. Our results therefore suggest that both the organization and development of the primate optic chiasm differ markedly from that revealed in rodents and carnivores.