Neuroscience
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Comparative Study
Local sensory ganglion ischemia induced by endothelin vasoconstriction: vulnerability of diabetic neurons and microvessels.
In some disorders of the peripheral nervous system, it is relevant to understand how sensory neurons respond to selective ganglion ischemia. Sensory dorsal root ganglia may be susceptible to ischemic damage and irretrievable neuron loss because of their metabolic requirements. In diabetes, heightened sensitivity to ischemia associated with elevated endothelin levels might render ganglia particularly vulnerable. ⋯ Both intraganglionic axons and downstream sural sensory axons developed evidence of axonal degeneration. Local endothelin-induced vasoconstriction of microvessels supplying dorsal root ganglia provides a selective model of ischemia. Diabetic vessels and neurons, exposed to a greater depth and duration of ischemia from endothelin, are especially vulnerable.
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Inflammation and reduced forebrain norepinephrine are features of Alzheimer's disease that may interact to contribute to the degeneration of specific neural systems. We reproduced these conditions within the basal forebrain cholinergic system, a region that is vulnerable to degeneration in Alzheimer's disease. Tumor necrosis factor-alpha was infused into the basal forebrain of young mice pretreated with a norepinephrine neuronal toxin, N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP4), with the expectation that the loss of noradrenergic input would enhance the loss of cholinergic neurons. ⋯ Infusion of tumor necrosis factor-alpha into DSP4-pretreated mice also reduced cortical choline acetyltransferase activity on the side of the infusion; however, the decline was not significantly greater than that produced by the infusion of tumor necrosis factor-alpha alone. The neurodegeneration seen may be indirect since a double-immunofluorescence investigation did not find evidence for the co-existence of tumor necrosis factor-alpha type I receptors on choline acetyltransferase-positive cells in the basal forebrain. The results suggest that noradrenergic cell loss in Alzheimer's disease does not augment the consequences of the chronic neuroinflammation and does not enhance neurodegeneration of forebrain cholinergic neurons.
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Comparative Study
Propagation pattern of entorhinal cortex subfields to the dentate gyrus in the guinea-pig: an electrophysiological study.
Anatomical studies demonstrated that neurons located in the superficial layers of the medial and lateral aspects of the rat entorhinal cortex (EC) project to temporal and septal portions of both the dentate gyrus (DG) and the CA1 region of the hippocampus, respectively. In the present study we investigated with electrophysiological techniques the propagation pattern of different EC subfields to the DG of the in vitro isolated brain of the guinea-pig. Laminar field potential profiles from different portions of the DG were recorded with multi-channel silicon probes following direct stimulation of the ipsilateral EC surface performed in different positions under direct visual control. ⋯ The EC-evoked monosynaptic DG potentials were followed by disynaptic responses coupled with sinks located in the inner molecular layer, proximal to the EC-induced sink, where intra-DG associative synapses were demonstrated by anatomical studies. The present detailed topographical study of the EC connections with the DG in the guinea-pig demonstrates with an electrophysiological approach a projection pattern similar, even if not identical, to that described with tracer techniques in the rat. This report is essential for future studies of the dynamic parahippocampal-hippocampal interactions in the guinea-pig, and in particular in the isolated guinea-pig brain preparation.
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Comparative Study
Frequency-dependent expression of corticotropin releasing factor in the rat's cerebellum.
Corticotropin releasing factor (CRF), localized in extrinsic afferents in the mammalian cerebellum, is defined as a neuromodulator within cerebellar circuits, and appears to be an essential element in the generation of long term depression, a proposed mechanism for motor learning. These physiological studies are based on exogenous application of CRF and do not address potential mechanisms that may influence endogenous release of the peptide. In the present study, immunohistochemistry was used to analyze changes in the lobular distribution of CRF-like immunoreactivity (LIR). ⋯ Quantitatively, the RIA studies indicate that there is a significant increase in CRF levels in the vermis, hemispheres and flocculus that correlates closely with stimulation frequency. In conclusion, stimulation of cerebellar afferents induces a significant change in the distribution and levels of CRF-LIR in climbing fibers, mossy fibers and glial cells. This suggests that the modulatory effects ascribed to CRF may influence a greater number of target neurons when levels of activity in afferent systems is increased.
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Comparative Study
The mouse nac1 gene, encoding a cocaine-regulated Bric-a-brac Tramtrac Broad complex/Pox virus and Zinc finger protein, is regulated by AP1.
NAC1 cDNA was identified as a novel transcript induced in the nucleus accumbens from rats chronically treated with cocaine. NAC1 is a member of the Bric-a-brac Tramtrac Broad complex/Pox virus and Zinc finger family of transcription factors and has been shown by overexpression studies to prevent the development of behavioral sensitization resulting from repeated cocaine treatment. This paper reports the cloning and characterization of the corresponding gene. ⋯ Activation of immediate early genes such as c-fos and c-jun following chronic drug treatments has been well characterized. The present data describe one potential regulatory cascade involving these transcription factors and activation of NAC1. Identification of drug induced alterations in gene expression is key to understanding the types of molecular adaptations underlying addiction.