Neuroscience
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Aquaporin 1 (AQP1) is a member of a family of small, integral membrane water-transporting proteins, which facilitate water movement across cell membranes in response to osmotic gradients. Several papers have studied the expression and function of the AQPs in the central nervous system. However, little is known about the AQPs in the peripheral nervous system (PNS). ⋯ At the nodes of Ranvier, AQP1 co-localizes with actin in the paranodal regions of the nerve. Therefore, AQP1 might play an important role in myelin homeostasis maintaining the thermodynamic equilibrium across the plasma membrane in myelinated axons during electrical activity. Also the expression of AQP1 in non-myelinating Schwann cells supports the involvement of AQP1 in pain perception.
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The transcription factor Otx1 is specifically expressed in layer V pyramidal cells (L5PCs) in the cerebral cortex. Otx1 null mutant mice have a defect in the developmental axon pruning of L5PCs and show epileptic seizures. However, the role of Otx1 in electrophysiology, morphology and synaptology of the cortical neurons has not been fully investigated. ⋯ Taken together, it suggests an enhanced activity of neuronal network in the cortex of Otx1 mutant mice. These data indicate that the Otx1 expression is essential for the normal development of dendritic morphology, intrinsic electrophysiology and synaptic dynamics of L5PCs. This study provides new insights into molecular mechanisms underlying the spatial and temporal regulation of neuronal and synaptic properties of L5PCs, and improves our understanding on the generation of epileptic seizures.
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There is increasing evidence implicating astrocytes in multiple forms of chronic pain, as well as in the specific context of chemotherapy-induced peripheral neuropathy (CIPN). However, it is still unclear what the exact role of astrocytes may be in the context of CIPN. Findings in oxaliplatin and paclitaxel models have displayed altered expression of astrocytic gap junctions and glutamate transporters as means by which astrocytes may contribute to observed behavioral changes. ⋯ These changes were prevented by co-treatment with minocycline. Follow-up Western blotting data showed a shift in connexin 43 from a non-phosphorylated state to a phosphorylated state, indicating increased trafficking of expressed connexin 43 to the cell membrane. These data suggest that increases in behavioral sensitivity to cutaneous stimuli may be tied to persistent synaptic glutamate resulting from increased calcium flow between spinal astrocytes.
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The central vestibular system plays an important role in higher neural functions such as self-motion perception and spatial orientation. Its ability to store head angular velocity is called velocity storage mechanism (VSM), which has been thoroughly investigated across a wide range of species. However, little is known about the mouse VSM, because the mouse lacks typical ocular responses such as optokinetic after nystagmus or a dominant time constant of vestibulo-ocular reflex for which the VSM is critical. ⋯ On the other hand, to reach a plateau state of bias, a higher frequency rotation or a larger gravito-inertial force was considered to be necessary than other larger animals. Compared with modulation, the bias had a more variable profile, suggesting an inherent complexity of higher-order neural processes in the brain. Our data provide the basis for further study of the central vestibular system in mice, however, the underlying individual variability should be taken into consideration.
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We previously demonstrated that hydrogen peroxide concentration ([H2O2]) significantly increases after spinal cord injury (SCI). The present study explored (1) whether SCI-elevated [H2O2] is sufficient to induce oxidation and cell death, (2) if apoptosis is a pathway of H2O2-induced cell death, and (3) whether H2O2-induced oxidation and cell death could be reversed by treatment with the catalytic antioxidant Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP). H2O2 was perfused through a microcannula into the uninjured rat spinal cord to mimic the conditions induced by SCI. ⋯ H2O2 also significantly increased cell loss and the numbers of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-(dUTP)-biotin nick end labeling (TUNEL)-positive and active caspase-3-positive neurons by 2.3-, 2.8-, and 5.6-fold compared to ACSF controls, respectively. Our results directly and unequivocally demonstrate that SCI-elevated [H2O2] contributes to post-SCI MLP, protein, and DNA oxidation to induce cell death. Therefore, we conclude that (1) the role of H2O2 in secondary SCI is pro-oxidation and pro-cell death, (2) apoptosis is a pathway for SCI-elevated [H2O2] to induce cell death, (3) caspase activation is a mechanism of H2O2-induced apoptosis after SCI, and (4) MnTBAP treatment significantly decreased H2O2-induced oxidation, cell loss, and apoptosis to the levels of ACSF controls, further supporting MnTBAP's ability to scavenge H2O2 by in vivo evidence.