Brain research
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Comparative Study
The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.
Cortical dysplasia (CD) is often associated with pharmacoresistant epilepsy. Previous studies showed increased expression of the NMDA receptor subunit NR2B in dysplastic and epileptic human neocortex. We tested the hypothesis that differential increase of NR2B constitutes an epileptogenic mechanism in humans. ⋯ In both dysplastic and non-dysplastic slices, EFP were suppressed by a non-specific NMDAR antagonist (APV) or AMPA receptor antagonist (CNQX). These results provide additional evidence that the differential expression of NR2B in dysplastic human neocortex may play a role in the expression of in-situ epileptogenesis in human CD. NR2B may constitute a target for new diagnostic and pharmacotherapeutic approaches.
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The central body temperature (T(b)) regulation system during hibernation was investigated in Syrian hamsters of either sex. Hibernation induced in Syrian hamsters by housing them in a cold room under short day-light/dark cycle was confirmed by marked reductions in the heart rate, T(b) and respiratory rate. The hibernation of hamsters was classified into (i) entrance, (ii) maintenance and (iii) arousal phases according to T(b) changes. ⋯ Furthermore, ICV injection of the anti-TRH antibody ameliorated the T(b) elevations induced by tactile stimulation. These results suggest that activation of the A1-receptor by adenosine is important for the generation of hypothermia in the entrance phase, and that activation of the mu1-opioid receptor by opioid peptides is required for perpetuation of hypothermia in the maintenance phase. In addition, TRH is a key endogenous substance involved in T(b) elevations during the arousal phase of hibernating hamsters.
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Neuropeptide W-23 (NPW23) is an endogenous ligand of both GPR7 and GPR8, and neuropeptide B (NPB) is an endogenous ligand of GPR7. GPR7 mRNA has been detected in regions of the cortex, the hippocampus, the hypothalamus, and the spinal cord in the rat, but GPR8 has not been found in rodents. GPR7 and GPR8 receptors have structural features in common with both opioid and somatostatin receptors. ⋯ I.t. injection of either 10 microg of NPW23 or 10 microg of NPB had no effect in the mechanical nociceptive test. I.t. injection of either 10 microg of NPW23 or 10 microg of NPB significantly suppressed the expression of Fos-like immunoreactivity of the L4-5 spinal dorsal horn induced by paw formalin injection. These data suggest that both spinally-applied NPW23 and NPB suppressed the input of nociceptive information to the spinal dorsal horn, produced an analgesic effect in the formalin test, and attenuated the level of mechanical allodynia in the carrageenan test, and that either spinally applied NPW23 or spinally applied NPB had no effect in the physiological condition.
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Sprague-Dawley rats with unilateral lesion of the medial forebrain bundle by 6-hydroxydopamine showed marked decrease in the expression of dopamine D1 and D2 receptors in the prefrontal cortex. Simvastatin (10 mg/kg/day for 4 weeks) restored receptor expression to control levels. Given the association of dopaminergic dysfunction in the prefrontal cortex and cognitive deficits in Parkinson's disease, these findings may have implication in the treatment of cognitive decline in advanced Parkinson's disease.
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, characterized by the degeneration of upper and lower motor neurons (MNs). Central nervous system features include a loss of Betz cells and other pyramidal cells from sensorimotor cortex. The intrinsic mechanism underlying this selective motor neuron loss has not been identified. ⋯ These results suggest that, not only has a PCD pathway been activated in the cortical MNs, but one that may be unique to ALS. Moreover, these findings suggest that earlier diagnosis and therapeutic intervention may be possible for successful treatment of ALS. Consequently, these enzymes may provide the biochemical markers to enable earlier diagnosis of ALS and molecular targets for the development of new therapeutic compounds.