Neuroscience
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Interaction between basal ganglia and cerebral cortex is critical for normal goal-directed behavior. In the present study we have used the immediate early gene zif/268, as functional marker to investigate how the stimulation of adenosine A2A receptors, i.e. of the "indirect" striatal output pathway, affects striatal and cortical function in "weaver" mouse, a genetic model of dopamine deficiency. Furthermore, we have examined the effect of A2A receptor stimulation on glutamate receptor expression in the "weaver" brain. ⋯ Furthermore, the up-regulation of epsilon2 subunit mRNA of the NMDA receptor, induced by CGS21680 administration, seen in striatum and cortex of the "weaver" mouse, would lead to overactivity of these receptors worsening dyskinesias. These results suggest adenosine to play a significant role in regulating striatal and cortical neurochemistry in a dopamine-depleted mouse. Blockade of these receptors by specific A2A antagonists could ameliorate parkinsonian symptoms.
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Comparative Study
Early increase of apoptosis-linked gene-2 interacting protein X in areas of kainate-induced neurodegeneration.
Apoptosis-linked gene-2 interacting protein X (Alix) is thought to be involved in both cell death and vesicular trafficking. We examined Alix expression 2 h, 6 h and 24 h after triggering seizure-dependent neuronal death by i.p. kainic acid injection. In the hippocampus, intense, transient immunolabelling was observed in the strata lucidum, oriens and radiatum, areas of high synaptic activity. ⋯ The increase persisted 24 h after kainate-injection in CA3 and the piriform cortex which are areas with massive swelling and numerous pyknotic neurons. This suggests that Alix may play an early role in the mechanisms leading to cell death. Taken together, our results suggest that Alix may be a molecular link between synaptic functioning and neuronal death.
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Previous studies have established the usefulness of endothelin-1 (ET-1) for the production of focal cerebral ischemia. The present study assessed the behavioral effects of focal ET-1-induced lesions of the sensorimotor cortex (SMC) in adult rats as well as cellular and structural changes in the contralateral homotopic motor cortex at early (2 days) and later (14 days) post-lesion time points. ET-1 lesions resulted in somatosensory and postural-motor impairments in the contralateral (to the lesion) forelimb as assessed on a battery of sensitive measures of sensorimotor function. ⋯ In comparison to sham-operated rats, in layer V of the motor cortex opposite the lesions, there were time- and laminar-dependent increases in the surface density of dendritic processes immunoreactive for microtubule-associated protein 2, in the optical density of N-methyl-D-asparate receptor (NMDA) subunit 1 immunoreactivity, and in the numerical density of cells immunolabeled for Fos, the protein product of the immediate early gene c-fos. These findings corroborate and extend previous findings of the effects of electrolytic lesions of the SMC. It is likely that compensatory forelimb behavioral changes and transcallosal degeneration play important roles in these changes in the cortex opposite the lesion, similar to previously reported effects of electrolytic SMC lesions.
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Abdominal surgery induces mu opioid receptor endocytosis in enteric neurons of the guinea-pig ileum.
Immunohistochemistry and confocal microscopy were used to investigate mu opioid receptor (muOR) internalization in enteric neurons of the guinea-pig ileum following abdominal surgery. The following surgical procedures were performed under halothane or isofluorane anesthesia: a) midline abdominal skin incision, b) laparotomy or c) laparotomy with intestinal manipulation. Gastrointestinal transit was evaluated by using a non-absorbable marker and measuring fecal pellet output. ⋯ M.), whereas it was significantly increased by laparotomy (46.5+/-6.1%; P<0.01 vs. controls) or laparotomy plus intestinal manipulation (40.5+/-6.1%; P<0.01 vs. controls) 30 min following surgery compared with controls. muOR endocytosis remained elevated at 4 h (38.6+/-1.2%; P<0.01 vs. controls), whereas it was similar to controls at 6 and 12 h (17.5+/-5.8% and 11.2+/-3.0%). muOR endocytosis occurred in cholinergic and nitrergic neurons. Gastrointestinal transit was significantly delayed by laparotomy or laparotomy plus intestinal manipulation (12.8+/-1.2 and 13.8+/-0.6 h vs. 7.0+/-0.5 in controls; P<0.01), but was not significantly changed by skin incision (8.2+/-0.6 h). The findings of the present study support the concept that the noxious stimulation caused by abdominal surgery induces release of endogenous opioids thus resulting in muOR endocytosis in neurochemically distinct enteric neurons. muOR internalization can serve as indirect evidence of opioid release and as a means to visualize neuronal pathways activated by opioids.
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Excitotoxic oligodendroglial death is one of the mechanisms which has been proposed to underlie demyelinating diseases of the CNS. We describe here functional consequences of excitotoxic lesions to the rabbit optic nerve by studying the visual evoked potentials (VEPs) measured in the visual cortex. Nerves were slowly infused with the excitotoxin kainate a subcutaneously implanted osmotic pump which delivered the toxin through a cannula onto the optic nerve. ⋯ These observations were confirmed and extended by immunohistochemical analyses using markers to neurofilaments, myelin basic protein and the oligodendrocyte marker APC. The results of the present paper indicate that the consequences of excitotoxicity in the optic nerve share functional and morphological alterations which are found in demyelinating disorders. In addition, this experimental paradigm may be useful to evaluate the functional recovery of demyelinated optic nerves following various repair strategies.