Neuroscience
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Aquaporin-4 (AQP4) is the predominant water channel in the neuropil of the central nervous system. It is expressed primarily in astrocytes, but also occurs in ependymocytes and endothelial cells. A striking feature of AQP4 expression is its polarized distribution in brain astrocytes and retinal Muller cells. ⋯ We propose that AQP4 works in concert with Kir4.1 and the electrogenic bicarbonate transporter NBC and that water flux through AQP4 contributes to the activity dependent volume changes of the extracellular space. Such volume changes are important as they affect the extracellular solute concentrations and electrical fields, and hence neuronal excitability. We conclude that AQP4-mediated water flux represents an integral element of brain volume and ion homeostasis.
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We previously measured the time courses of hydrogen peroxide (H2O2), hydroxyl radical (*OH), and catalytic iron increases following traumatic spinal cord injury (SCI). This study determines whether the SCI-elevated level of *OH causes cell death. OH was generated by administering H2O2 and Fe2+ at the concentrations attained following SCI, each through a separate microdialysis fiber inserted laterally into the gray matter of the cord. ⋯ It also reduced the numbers of TUNEL-positive neurons (P=0.01). Electron microscopy confirmed that generated *OH induced neuronal and glial death with characteristic features of both necrosis and apoptosis. We conclude that 1) SCI-elevated *OH is sufficient to induce both necrosis and apoptosis, criteria for identifying an endogenous secondary damaging agent; 2) MnTBAP reduces *OH-induced cell death, perhaps by removing H2O2 administered in the tissue, thereby blocking formation of *OH, and also by scavenging downstream reactive species.
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Comparative Study
Synaptic properties and postsynaptic opioid effects in rat central amygdala neurons.
An important output of amygdaloid nuclei, the central nucleus of the amygdala (CeA) not only mediates negative emotional behaviors, but also participates in the stimulus-reward learning and expression of motivational aspects of many drugs of abuse, and links environmentally stressful conditions such as fear to endogenous pain-inhibiting mechanisms. The endogenous opioid system in the CeA is crucial for both reward behaviors and environmental stress-induced analgesia. In this study using whole-cell voltage-clamp recordings, we investigated synaptic inputs and the postsynaptic effects of opioid agonists in CeA neurons. ⋯ In contrast, the kappa-opioid receptor agonist hyperpolarized only type B neurons. These results illustrate three types of CeA neurons with distinctive membrane properties and differential responses to opioid agonists. They may represent functionally distinct CeA cell groups for the integration and execution of CeA outputs in the aforementioned CeA functions.
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The expression of purinoceptor (P2)Y-subtypes on astrocytes in vivo under physiological conditions and after stab wound injury was investigated. Reverse transcriptase-polymerase chain reaction with specific primers for the receptor-subtypes P2Y1,2,4,6,12 in tissue extracts of the nucleus accumbens of untreated rats revealed the presence of all P2Y receptor mRNAs investigated. Double immunofluorescence visualized with laser scanning microscopy indicated the expression of the P2Y1,4 receptors on glial fibrillary acidic protein (GFAP)-labeled astrocytes under physiological conditions. ⋯ The non-selective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, the P2Y1 receptor antagonist N6-methyl-2'-deoxyadenosine 3',5'-bisphosphate and the P2Y1 receptor-antibody itself inhibited the agonist-induced effects. The data indicate the region-specific presence of P2Y receptors on astrocytes in vivo and their up-regulation after injury as well as the co-localization of P2X and P2Y receptor-subtypes on the same astrocyte. The dominant role of P2Y1 receptors in proliferation and the additional stimulation of non-P2Y1 receptors has been demonstrated in vivo suggesting the involvement of this receptor-type in the gliotic response under physiological and pathological conditions.
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Comparative Study
Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea.
Chronic intermittent hypoxia (CIH), as occurs in obstructive sleep apnea (SA), is associated with substantial cortico-hippocampal damage leading to impairments of neurocognitive, respiratory and cardiovascular functions. Previous studies in a rat model have shown that CIH increases brain cortical neuronal cell death. However, the molecular events leading to CIH-mediated neuronal cell death remain largely undefined. ⋯ Furthermore, exposure of mice to CIH induced caspase-3 activation and increased some cortical neuronal cell apoptosis. On the other hand, transgenic mice overexpressing Cu,Zn-superoxide dismutase exposed to CIH conditions had a lower level of steady-state ROS production and reduced neuronal apoptosis in brain cortex compared with that of normal control mice. Taken together, these findings suggest that the increased ROS production and oxidative stress propagation contribute, at least partially, to CIH-mediated cortical neuronal apoptosis and neurocognitive dysfunction.