The Journal of neuroscience : the official journal of the Society for Neuroscience
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Comparative Study
Elements in the 5' flanking sequences of the mouse low-affinity NGF receptor gene direct appropriate CNS, but not PNS, expression in transgenic mice.
We have initiated a characterization of the cis-acting regulatory elements of the murine low-affinity NGF receptor (p75NGFR) gene. Despite studies in cultured cells that suggest the p75NGFR promoter is constitutive, a detailed analysis of this promoter in five lines of transgenic mice demonstrated a high degree of cell-type specificity: 8.4 kb of 5' flanking sequence directs expression of a lacZ reporter to retinal and CNS neurons normally expressing p75NGFR. A transgene with 470 bp of 5' flanking sequence is also expressed in the CNS, but its regulation is aberrant, with a loss of basal forebrain expression. ⋯ Further regulatory elements are possibly required for expression in at least some sensory and sympathetic neurons in the PNS and in Schwann cells. To identify potential regulatory elements in the 470 bp of 5' flanking sequence from the smaller transgene, we compared the sequences of equivalent regions from the mouse, rat, and human p75NGFR genes. This "phylogenetic footprint" identified conserved motifs potentially important for the regulation of this gene in the CNS.
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Intraperitoneal administration of hypertonic saline is a potent stimulus to the "stress" responsive hypophysiotrophic parvicellular neurons of the hypothalamic paraventricular nucleus (PVN), as well as to magnocellular neurons of the hypothalamo-neurohypophysial system. Precise identification of the pathways gating information about the "stress" of intraperitoneal hypertonic saline to the PVN has not been ascertained earlier. In this study we demonstrate that intraperitoneal injection of hypertonic saline induces increased expression of c-fos immunoreactivity within neurons of the medial parvicellular division of the PVN, within the circumventricular organs surrounding the anteroventral tip of the third ventricle, and within the magnocellular neurons of the PVN and supraoptic nucleus. ⋯ In the brainstem, the "stressor" induced expression of c-fos-IR nuclei in almost all of the retrogradely labeled cells of the ventrolateral part of the medulla oblongata (A1 and C1), while only about 25% of the ChB-labeled cells of the caudal part of the nucleus of the solitary tract (A2) were concomitantly immunoreactive to c-fos. Within the parabrachial nucleus, only 20% of the ChB-labeled cells were also immunoreactive for c-fos. The present results provide evidence that information about the "stress" of intraperitoneal hypertonic saline is conveyed to both magnocellular neurons projecting to the neurohypophysis and hypophysiotrophic parvicellular neurons the PVN via afferent projections from a variety of neurons in the osmosensitive anteroventral tip of the third ventricle and visceromotor neurons of the parabrachial nucleus, the ventrolateral medulla and the nucleus of the solitary tract.
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Studies in mice and rats have shown that antinociception produced by intrathecal (i.t.) administration of opioids can be partially inhibited by intracerebroventricular (i.c.v.) administration of naloxone. In this study we tested the hypothesis that this inhibition by i.c.v. naloxone results from antagonism of supraspinal endogenous opioid-mediated antinociception produced by the action of i.t. opioids on an ascending antinociceptive pathway. In rats lightly anesthetized with urethane/alpha-chloralose, i.t. ⋯ Microinjection of naloxone methiodide into nucleus accumbens but not into the rostral ventral medulla (RVM) or the periaqueductal gray matter (PAG) antagonized the suppression of the JOR produced by i.t. DAMGO or lidocaine. The possibility that this ascending pathway may represent a source of spinal input to mesolimbic circuitry involved in setting the state of sensorimotor reactivity to noxious stimuli is discussed.
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Aged rats have impairments in several types of cognitive functions, including spatial working memory (WM), that are dependent upon the septohippocampal cholinergic system. The present series of experiments was designed to assess the effectiveness of pharmacological manipulations of the medial septal area (MSA) in order to influence the physiology of the septohippocampal pathway and, therefore, the brain functions in which this pathway participates. Aged (22MO) and young (4MO) Fischer-344 rats received microinfusions into the MSA with either saline, the muscarinic agonist, oxotremorine (OXO), or the muscarinic antagonist, scopolamine (SCOP). ⋯ SCOP produced a shift of the hippocampal theta to a higher frequency and a lower peak power, and a decrease in the initial slope of pEPSP. In 4MO rats, SCOP altered hippocampal theta similarly to 22MO, but did not affect the pEPSP slope. These results indicate that (1) cholinergic receptors in the MSA are a useful target for drugs to improve WM in aging rats, (2) age-related changes in the activity of the septohippocampal pathway may increase its sensitivity to drugs which alter its activity, and (3) alterations in hippocampal physiology may contribute differently to changes in WM in young and in old rats.
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The developmental stage at which nerve cells initially express specific neurotransmitters and their corresponding receptors remains elusive. In the present study, the distribution patterns of transcripts for the GABA-synthesizing enzyme, glutamate decarboxylase (GAD67), and specific GABAA receptor subunits were examined in the proliferative zone of the rat central nervous system using in situ hybridization. In order to define the DNA synthetic zone of the germinal matrix, tissue sections were taken from embryos whose mothers had been injected with 5-bromo-2'-deoxyuridine (BrdU) and had survived for 1 hr. ⋯ In clear contrast, GAD67 mRNA was abundant in the outer half of the germinal matrix (i.e., TZ or SV), and in the intermediate zone as well. Immunocytochemical staining of E17 neocortex with anti-GABA antibody revealed a well defined band of GABA-immunoreactive cells and processes in the SV and occasional positive cells in the VZ. It appears that cells in the proliferative zone may express GABA at the migratory stage, whereas cells in the VZ may express mRNAs for GABAA receptor alpha 4, beta 1, and gamma 1 subunits at the premigratory stage, just after completing cell division.(ABSTRACT TRUNCATED AT 400 WORDS)