Neuroscience
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Comparative Study
Changes in GABA(B) receptor mRNA expression in the rodent basal ganglia and thalamus following lesion of the nigrostriatal pathway.
Loss of striatal dopaminergic innervation in Parkinson's disease (PD) is accompanied by widespread alterations in GABAergic activity within the basal ganglia and thalamus. Accompanying changes in GABA(B) receptor binding have been noted in some basal ganglia regions in parkinsonian primates, suggesting that plasticity of this receptor may also occur in PD. However, the molecular mechanisms underlying the changes in receptor binding and the manner and extent to which different GABA(B) receptor mRNA subunits and splice-variants are affected remain unknown. ⋯ Expression of the GABA(B(1a)) variant was significantly increased in the substantia nigra pars reticulata (33+/-2%), entopeduncular nucleus (26+/-1%) and the subthalamic nucleus (16+/-1%). Since these regions all receive reduced GABAergic innervation following nigrostriatal tract lesioning, it is possible that the increased expression occurs as a compensatory measure. In conclusion, these data demonstrate that GABA(B) receptor genes exhibit regional- and subunit/variant-specific plasticity at the molecular level under parkinsonian conditions.
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Glial cell line-derived neurotrophic factor (GDNF) is necessary for the development of sensory neurons, and appears to be critical for the survival of dorsal root ganglion (DRG) cells that bind the lectin IB4. Intrathecal infusion of GDNF has been shown to prevent and reverse the behavioral expression of experimental neuropathic pain arising from injury to spinal nerves. This effect of GDNF has been attributed to a blockade of the expression of the voltage gated, tetrodotoxin-sensitive sodium channel subtype, Na(V)1.3, in the injured DRG. ⋯ These observations suggest that high dose, exogenous GDNF has a broad neuroprotective role in injured primary afferent. The receptor(s) that mediates these effects of GDNF is not known. GDNF's ability to block neuropathic pain states is not likely to be specific to Na(V)1.3 expression.
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Comparative Study
Intraseptal infusion of oxotremorine impairs memory in a delayed-non-match-to-sample radial maze task.
The medial septal nucleus is part of the forebrain circuitry that supports memory. This nucleus is rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive-enhancing drugs. Septal neurons, primarily cholinergic and GABAergic, innervate the entire hippocampal formation and regulate hippocampal formation physiology and emergent function. ⋯ The persistent deficit contrasts with the acute amnestic effects of other intraseptally administered drugs including the cholinomimetics carbachol and tacrine. Thus, intraseptal oxotremorine produced a preferential disruption of memory consolidation as well as a persistent alteration of medial septal circuits. These findings are discussed with regards to multi-stage models of hippocampal-dependent memory formation and the further development of therapeutic strategies in the treatment of mild cognitive impairment as well as age-related decline and Alzheimer's dementia.
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Comparative Study
P2 receptors in satellite glial cells in trigeminal ganglia of mice.
There is strong evidence for the presence of nucleotide (P2) receptors in sensory neurons, which might play a role in the transmission of pain signals. In contrast, virtually nothing is known about P2 receptors in satellite glial cells (SGCs), which are the main glial cells in sensory ganglia. We investigated the possibility that P2 receptors exist in SGCs in murine trigeminal ganglia, using Ca(2+) imaging, patch-clamp recordings, and immunohistochemistry. ⋯ Patch-clamp recordings of SGCs did not reveal any inward current due to ATP. Therefore, there was no evidence for the activation of ionotropic P2X receptors under the present conditions. The results indicate the presence of functional nucleotide (P2Y) receptors in SGCs.
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Comparative Study
Differential psychostimulant-induced activation of neural circuits in dopamine transporter knockout and wild type mice.
Dopamine (DA) is a neurotransmitter that has been implicated in a wide variety of psychiatric disorders that include attention deficit-hyperactivity disorder (ADHD), schizophrenia, and drug abuse. Recently, we have been working with a mouse in which the gene for the DA transporter (DAT) has been disrupted. This mouse is hyperactive in the open field, displays an inability to inhibit ongoing behaviors, and is deficient on learning and memory tasks. ⋯ Since the DAT gene is disrupted in the KO mouse, these findings suggest that dopaminergic mechanisms may mediate the WT responses, whereas non-dopaminergic systems predominate in the mutant. In the mutants, it appears that limbic areas and non-dopaminergic transmitter systems within these brain regions may mediate responses to psychostimulants. Inasmuch as the KO mouse may represent a useful animal model for ADHD and because psychostimulants such as cocaine are reinforcing to these animals, our results may provide some useful insights into the neural mechanisms-other than DA-that may contribute to the symptoms of ADHD and/or drug abuse in human patients.