Neuroscience
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Susceptibility to develop Parkinson's disease has been linked to abnormalities of P450 enzyme function. Multiple P450 enzymes are expressed in brain but the relationship of these to Parkinson's disease is unknown. We have investigated the expression of P450 enzymes in the rat substantia nigra and their co-localization in tyrosine hydroxylase-positive neurons and astrocytes. ⋯ At least two P450 enzymes are found in nigral dopamine containing cells and one, namely CYP2E1, is selectively localized to this cell population. CYP2E1 is a potent generator of free radicals which may contribute to nigral pathology in Parkinson's disease. The expression of CYP2E1 in dopaminergic neurons in substantia nigra raises the possibility of a causal association with Parkinson's disease.
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Whole-cell patch-clamp recordings were obtained from nodose ganglion neurons acutely dissociated from 10-30-day-old rats to characterize the Ca2+ channel types that are modulated by GABA(B) and mu-opioid receptors. Five components of high-threshold current were distinguished on the basis of their sensitivity to blockade by omega-conotoxin GVIA, nifedipine, omega-agatoxin IVA and omega-conotoxin MVIIC. Administration of the mu-opioid agonist H-Tyr-D-Ala-Gly-Phe(N-Me)-Gly-ol (0.3-1 mM) or the GABA(B) agonist baclofen in saturating concentrations suppressed high-threshold Ca2+ currents by 49.9+/-2.4% (n=69) and 18.7+/-2.1% (n=35), respectively. ⋯ These data indicate that in nodose ganglion neurons mu-opioid receptors are negatively coupled to N-, P- and Q-type channels as well as to a fourth, unidentified toxin-resistant Ca2+ channel. In contrast, GABA(B) receptors are coupled only to N-type channels. Furthermore, the results do not support a role for either protein kinase C or A in the modulatory pathway(s) coupling mu-opioid and GABA(B) receptors to Ca2+ channels, but rather lend credence to the notion that the signalling mechanisms utilized by these two receptors might simply compete for inhibitory control of a common pool of N-type channels.
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Gamma-Aminobutyric acid (GABA) receptors are present in membrane preparations from Hydra vulgaris, one of the most primitive organisms with a nervous system. These receptors are sensitive to muscimol and benzodiazepines and appear to be important in the regulation of the feeding response. The effects of neurosteroids, general anaesthetics, and GABA antagonists on GABA(A) receptors in membranes prepared from Hydra and on the feeding response have now been investigated. ⋯ Alphaxalone (10 microM) similarly increased (+33%) the effect of glutathione. The effects of steroids on the feeding response were inhibited by SR 95531 in a dose-dependent manner; t-butylbyclophosphorothyonate (1 microM), a specific Cl- channel blocker, which per se, like picrotoxin but not bicuculline, shortened the duration of the response, also counteracted the steroids effects at 1 microM. These results suggest that the modulation of GABA(A) receptors by steroids is an ancient characteristic of the animal kingdom and that the pharmacological properties of these receptors have been highly conserved through evolution.
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Single-unit recording combined with iontophoresis of dopamine, GABA, and glutamate was used in awake, unrestrained rats to characterize the electrophysiological and receptor properties of neurons in the ventral tegmental area under naturally occurring behavioural conditions. All isolated ventral tegmental area units (n=90) were analysed and compared with cells (n=58) recorded from dorsally adjacent areas of the pre-rubral area and red nucleus. Two distinct neuronal groups were identified in the ventral tegmental area: units with triphasic, long-duration spikes (78/90) and units with biphasic, short-duration spikes (12/90). ⋯ Type I, long-spike units match the characteristics of histochemically-identified dopamine neurons, and they appear to express dopamine autoreceptors, which may explain the relatively slow, stable rate of activity and the limited responsiveness to excitatory inputs. Although the nature of the other long-spike units in our sample is unclear, they may include dopamine neurons without autoreceptors as well as non-dopamine cells. The heterogeneity of ventral tegmental area neurons is an important consideration for further attempts to assess the role of the mesocorticolimbic dopamine system in motivated behaviour.
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Gap junctions are intercellular channels which mediate the traffic of ions and a variety of molecular messengers between contiguous cells. Here, we report on the possibility that atypical gap junctions develop between heterologous tissues, such as regenerating nerve axons and Schwann cells, during peripheral nerve regeneration in adult rats. ⋯ Biocytin, a small molecular weight dye, was transported from regenerating axons into adjoining Schwann cells. The present findings suggest that regenerating axons communicate directly with adjacent Schwann cells through small gap junctions, which may play a role in the mechanism of regeneration following nerve transection.