Neuroscience
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Mice deficient in the water channel aquaporin-4 (AQP4) demonstrate increased seizure duration in response to hippocampal stimulation as well as impaired extracellular K+ clearance. However, the expression of AQP4 in the hippocampus is not well described. In this study, we investigated (i) the developmental, laminar and cell-type specificity of AQP4 expression in the hippocampus; (ii) the effect of Kir4.1 deletion on AQP4 expression; and (iii) performed Western blot and RT-PCR analyses. ⋯ This study is the first to examine subregional AQP4 expression during development of the hippocampus. The strikingly high expression of AQP4 in the CA1 SLM and DG ML identifies these regions as potential sites of astrocytic K+ and H2O regulation. These results begin to delineate the functional capabilities of hippocampal subregions and cell types for K+ and H2O homeostasis, which is critical to excitability and serves as a potential target for modulation in diverse diseases.
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An immunocytochemical comparison of vGluT1 and vGluT3 in the cochlear nucleus (CN) of deafened versus normal hearing rats showed the first example of vGluT3 immunostaining in the dorsal and ventral CN and revealed temporal and spatial changes in vGluT1 localization in the CN after cochlear injury. In normal hearing rats vGluT1 immunostaining was restricted to terminals on CN neurons while vGluT3 immunolabeled the somata of the neurons. This changed in the ventral cochlear nucleus (VCN) 3 days following deafness, where vGluT1 immunostaining was no longer seen in large auditory nerve terminals but was instead found in somata of VCN neurons. ⋯ Therefore, loss of peripheral excitatory input results in co-localization of vGluT1 and vGluT3 in VCN neuronal somata. Postsynaptic glutamatergic neurons can use retrograde signaling to control their presynaptic inputs and these results suggest vGluTs could play a role in regulating retrograde signaling in the CN under different conditions of excitatory input. Changes in vGluT gene expression in CN neurons were found 3 weeks following deafness using qRT-PCR with significant increases in vGluT1 gene expression in both ventral and dorsal CN while vGluT3 gene expression decreased in VCN but increased in DCN.
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Spiral ganglion neurons (SGNs) extend processes that interact with Schwann cells (SCs) and with oligodendrocytes (OLs) and astrocytes (ACs). We investigated the ability of these glial cells to support SGN neurite growth. In the presence of cultured ACs, OLs and SCs, SGN neurites tended to follow SCs and OLs and cross-over ACs. ⋯ In explants plated on the borders of cultured OL-SC or AC-SC groups, more neurites extended onto SCs compared with OLs and ACs. Conditioned media (CM) from OL or AC cultures did not reduce neurite length, implying that the inhibition of neurite growth by central glia is not due to soluble factors. Taken together, these results demonstrate that homogeneous populations of central glia inhibit SGN neurite growth.
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The non-competitive N-methyl-D-aspartate NMDA receptor antagonist ketamine, a dissociative anesthetic capable of inducing analgesia, is known to have psychotomimetic actions, but the detailed mechanisms remain unclear because of its complex properties. The present study elucidated neural mechanisms of the effect of ketamine, at doses that exert psychotomimetic effects without anesthetic and analgesic effects, by evaluating cortical synaptic responses in vivo. Systemic administration (i.p.) of low (1 and 5 mg/kg), subanesthetic (25 mg/kg) and anesthetic (100 mg/kg) doses of ketamine dose-dependently decreased hippocampal stimulation-evoked potential in the medial prefrontal cortex (mPFC) in freely moving rats. ⋯ Ketamine (5 mg/kg, i.p.)-induced synaptic depression was blocked by pretreatment with dopamine D1 receptor antagonist SCH 23390 (10 μg/rat, i.c.v.) but not dopamine D2 receptor antagonist haloperidol (1.5 mg/kg, i.p.), suggesting that dopaminergic modulation mediated via D1 receptors are involved in the synaptic effects of ketamine. Furthermore, ketamine (5 mg/kg, i.p.)-induced synaptic depression was prevented also by GABAA receptor antagonist bicuculline (0.2 or 2 μg/rat, i.c.v.). These findings suggest that ketamine at the dose that exerts psychotomimetic symptoms depresses hippocampus-mPFC synaptic transmission through mechanisms involving dopaminergic modulation mediated via D1 receptors, which may lead to a net augmentation of synaptic inhibition mediated via GABAA receptors.
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It is well established that physical exercise can exert neuroprotection both in clinical settings and animal experiments. A series of studies have demonstrated that physical exercise may be a promising preconditioning method to induce brain ischemic tolerance through the promotion of angiogenesis, mediation of the inflammatory response, inhibition of glutamate over-activation, protection of the blood brain barrier (BBB) and inhibition of apoptosis. Through these mechanisms, exercise preconditioning may reduce the neural deficits associated with ischemia and the development of brain infarction and thus provide brain ischemic tolerance. An awareness of the benefits of exercise preconditioning may lead more patients to accept exercise therapy in cases of ischemic stroke.