Brain research
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Fast glutamatergic and GABAergic transmission in the central nucleus of the inferior colliculus (ICC), a major auditory midbrain structure, is mediated respectively by alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid (AMPA) and gamma-aminobutyric acid (GABA)(A) receptors. In this study, we used whole-cell patch clamp recordings in brain slices to investigate the effects of activation of metabotropic glutamate receptors (mGluRs) on synaptic responses mediated by AMPA and GABA(A) receptors in ICC neurons of young rats. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) mediated respectively by AMPA and GABA(A) receptors were elicited by stimulation of the lateral lemniscus, the major afferent pathway to the ICC. ⋯ The agonists for groups I and III, (RS)-3,5-dihydroxyphenylglycine (DHPG) and L-SOP, respectively, did not affect AMPA or GABA(A) receptor-mediated responses. The reduction of the synaptic responses by LY379268 was accompanied by a substantial increase in a ratio of the second to the first AMPA receptor-mediated EPSCs and GABA(A) receptor-mediated IPSCs to paired-pulse stimulation. The results suggest that group II mGluRs regulate both fast glutamatergic and GABAergic synaptic transmission in the ICC, probably through a presynaptic mechanism due to reduction of transmitter release.
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It has been proved that chronic administration and pre-treatment with atorvastatin could protect brain tissue against ischemic injury. However, little is known regarding the effect of atorvastatin in the acute phase of ischemic stroke. This study investigated the potential neuroprotective effects of atorvastatin and underlying mechanisms in vivo. ⋯ Atorvastatin protected brain from damage caused by MCAO at the early stage; this effect may be through down-regulation of 12/15-LOX, p38MAPK and cPLA2 expressions, and ameliorating BBB permeability.
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Degeneration of noradrenergic neurons in the locus coeruleus (LC) and dysfunction of the prefrontal cortex were regarded as playing a specific role in the occurrence of non-motor symptoms in Parkinson's disease. The present study examined the spontaneous firing rate and firing pattern of medial prefrontal cortex (mPFC) pyramidal neurons, and effects of alpha(2)-adrenoceptor agonist UK-14,304 and antagonist yohimbine on the neuronal activity in rats with 6-hydroxydopamine lesions of the LC, medial forebrain bundle (MFB) and with combined MFB and LC lesions. ⋯ The local administration of UK-14,304 in the mPFC inhibited the firing activity of the pyramidal neurons in normal rats and rats with lesions of the LC, MFB and with combined LC and MFB lesions, while yohimbine increased the firing activity of the pyramidal neurons. These results indicate that the lesions of the LC lead to hyperactivity of mPFC pyramidal neurons in normal and MFB-lesioned rats, and the postsynaptic alpha(2)-adrenoceptors may partially mediate the inhibitory effects of LC-noradrenergic system on the firing activity of pyramidal neurons in the mPFC, suggesting that LC-noradrenergic system plays an important role in the functional disorders of mPFC in Parkinson's disease.
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Treatment with amyloid beta(1-42) (Abeta(1-42)) at 1microM for 60min increased phagocytosis of latex beads by cultured rat microglia. This increase was reduced dose-dependently by prostaglandin E(2) (PGE(2)), but PGD(2), PGF(2alpha), iloprost, or U-46619 had no effects. PGE(2) also reduced the phagocytosis of fluorescent-labeled Abeta(1-42). ⋯ On the other hand, Abeta(1-42)-induced phagocytosis was not affected by SC-560, a cyclooxygenase-1 (COX-1) inhibitor, NS-398, a COX-2 inhibitor, or ibuprofen, a non-specific COX inhibitor. Abeta(1-42) or PGE(2) had little effect on the expression levels of COX-1 or COX-2. These results indicate that Abeta(1-42)-induced microglial phagocytosis is reduced by PGE(2) through EP2.
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Traumatic brain injury can initiate an array of chronic neurological deficits, effecting executive function, language and sensorimotor integration. Mechanical forces produce the diffuse pathology that disrupts neural circuit activation across vulnerable brain regions. The present manuscript explores the hypothesis that the extent of functional activation of brain-injured circuits is a consequence of initial disruption and consequent reorganization. ⋯ In the thalamus, the delayed restoration of plasticity markers may explain the broad distribution of neuronal activation extending into the striatum and hippocampus with whisker stimulation. The sprouting of diffuse-injured circuits into diffuse-injured tissue likely establishes maladaptive circuits responsible for behavioral morbidity. Therapeutic interventions to promote adaptive circuit restructuring may mitigate post-traumatic morbidity.