Journal of neuroscience research
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Spinal cord injury (SCI) leads to a complex sequence of cellular responses, including astrocyte activation, oligodendrocyte death, and ependymal cell proliferation. Inhibitors of DNA binding (Id1, Id2, Id3) belong to a helix-loop-helix (HLH) gene family. Id genes have been implicated in playing a vital role in the proliferation of many cell types, including astrocytes and myoblasts. ⋯ Cells having a neural progenitor morphology and the marker nestin appeared after SCI and they expressed Id1, Id2, and Id3 mRNA. Interestingly, some Rip+ oligodendrocytes located in the areas close to the central canal expressed Id3 mRNA after injury. In conclusion, Id genes are upregulated in a time-dependent manner in astrocytes, oligodendrocytes, and neural progenitor subpopulations after SCI, suggesting that they play major roles in cellular responses following SCI.
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Comparative Study
Monitoring arterio-venous differences of glucose and lactate in the anesthetized rat with or without brain damage with ultrafiltration and biosensor technology.
Continuous monitoring of arterio-venous glucose and lactate differences may serve as a diagnostic tool to assess normal brain function and brain pathology. We describe a method and some results obtained with arterio-venous measurements of glucose and lactate in the blood of the halothane-anesthetized rat and after brain injury. The method is based on low flow rate ultrafiltration for continuous collection of blood filtrate combined with flow injection analysis and biosensors for the detection of glucose and lactate. ⋯ Net cerebral lactate efflux and glucose uptake was seen under control conditions and at low blood lactate levels. During brain injury both lactate release and glucose uptake were reduced and there was a net lactate influx at high arterial lactate levels. These results indicate that the flux of lactate in and out of the brain is not only dependent on the lactate concentration in the brain, but on blood levels as well, possibly because of bi-directional flux through the monocarboxylate transporter type 1.
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Nicotine and other nicotinic acetylcholine receptor agonists have been shown to exert neuroprotective actions in vivo and in vitro by an as yet unknown mechanism. Even the identification of the subtype of nicotinic receptor(s) mediating this action has not been determined. In neural cell lines, the induction of cytoprotection often requires exposure to nicotine for up to 24 hr to produce a full protective effect. ⋯ Under similar conditions of incubation, the nicotinic receptor agonist cytisine (that was least effective in terms of neuroprotection) failed to increase the number of [(125)I]alphaBGT binding sites. Cells expressing increased levels of cell surface [(125)I]alphaBGT binding sites received added neuroprotective benefit from nicotine. Thus the induced upregulation of the alpha7 subtype of nicotinic receptors during chronic exposure to nicotine may be responsible for the drug's neuroprotective action.
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The main objective of the present study was to develop an alternative singly-transgenic (tg) hAPP model where amyloid deposition will occur at an earlier age. For this purpose, we generated lines of tg mice expressing hAPP751 cDNA containing the London (V717I) and Swedish (K670M/N671L) mutations under the regulatory control of the murine (m)Thy-1 gene (mThy1-hAPP751). In the brains of the highest (line 41) and intermediate (lines 16 and 11) expressers, high levels of hAPP expression were found in neurons in layers 4-5 of the neocortex, hippocampal CA1 and olfactory bulb. ⋯ Mice from line 11 developed diffuse amyloid deposits at 11 months of age, whereas mice from line 16 did not show evidence of amyloid deposition. Analysis of Abeta by ELISA showed that levels of Abeta(1-40) were higher in mice that did not show any amyloid deposits (line 16), whereas Abeta(1-42) was the predominant species in tg animals from the lines showing plaque formation (lines 41 and 11). Taken together this study indicates that early onset plaque formation depends on levels of Abeta(1-42).
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Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family and regulates the survival, differentiation, and maintenance of function in different neuronal populations. BDNF is strongly expressed in hypothalamic neurons, where it exerts long- or short-lasting actions. Because glutamate has been associated with regulations of hypothalamic hormones, we examined the regulation of the four promoters of the BDNF gene by glutamate in fetal hypothalamic neurons. ⋯ Actinomycin D blocked the increase of all transcripts, whereas cycloheximide treatment inhibited stimulation only of exon I and II mRNAs. Trk B mRNA was rapidly and transiently reduced after glutamate application. Our results demonstrate that glutamate 1) regulates BDNF mRNA expression at an early developmental stage in hypothalamic neurons and 2) exerts a differential regulation of BDNF transcripts.