Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Olfactory Cortex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed1996

Steady-state methadone in rats does not change mRNA levels of corticotropin-releasing factor, its pituitary receptor or proopiomelanocortin.

Male Fischer rats received either methadone (a long-acting opioid agonist, 10 mg/kg/day) or saline (24 microliters/day) subcutaneously by osmotic minipumps for 7 days. Chronic steady-state methadone administration did not alter (a) corticotropin-releasing factor (CRF) mRNA in the hypothalamus, (b) proopiomelanocortin (POMC) and CRF type 1 receptor (CRF-R1) mRNAs in the anterior lobe and neurointermediate/posterior lobe of the pituitary, or (c) circulating levels of corticosterone. No change was found in levels of either POMC mRNA in the hypothalamus and amygdala, or CRF mRNA in the frontal cortex, olfactory bulb and amygdala. These results demonstrate that neither the activity of the hypothalamic-pituitary-adrenal axis, nor the beta-endorphin and CRF systems in the brain, are altered by steady-state occupancy of opioid receptors with the long-acting opioid agonist methadone.

Animals↗
PubMed1997

Interactions between cocaine and (-)-DS 121: studies with 2-deoxyglucose autoradiography and microdialysis in the rat brain.

(-)-DS 121 [S-(-)-3-(3-cyanophenyl)-N-n-propyl piperidine], a dopamine autoreceptor preferring antagonist, has been shown to stimulate locomotor activity and induce conditioned place preference. However, the drug fails to facilitate intracranial self-stimulation or substitute for cocaine in cueing experiments, and it blocks cocaine self-administration. In the present study using 2-deoxyglucose autoradiography, (-)-DS 121 (at 50 but not 15 mg/kg i.p.) significantly and selectively increased local cerebral glucose utilization in the olfactory cortex, medial and lateral septum, hippocampal areas, substantia nigra pars reticulata, caudate, and mammillary body. Local cerebral glucose utilization was depressed in caudal areas of the cortex. Interestingly, however, both doses of (-)-DS 121 blocked the increases in local cerebral glucose utilization produced by 5 mg/kg i.v. cocaine. The present study also evaluated the effects of (-)-DS 121 of extracellular striatal dopamine levels using microdialysis in freely moving rats. By itself, 15 mg/kg of (-)-DS 121 increased extracellular striatal dopamine levels to approximately 300% of controls. Cocaine (5 mg/kg i.v.) produced a 370% increase in striatal dopamine levels. When rats were pretreated with (-)-DS 121, a subsequent dose of cocaine augmented the increase in extracellular striatal dopamine to 870% of controls. The results support the contention that (-)-DS 121 possesses weak cocaine-mimetic effects and that its antagonism of cocaine's subjective effects are due to interactions with dopamine at postsynaptic sites. It is hypothesized that, like other preferential autoreceptor antagonists, (-)-DS 121 may be useful as a pharmacotherapy in drug addiction.

Animals↗
PubMed1999

Ischemia induces metallothionein III expression in neurons of rat brain.

Metallothionein III (MT-III) is a brain-specific member of the metallothionein family and binds zinc in vivo. In order to confirm the precise localization of MT-III in normal rat brain and the change of MT-III expression after transient whole brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT-III. Immunohistochemical analysis revealed that MT-III in normal brain is localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus, dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum. This expression pattern of MT-III was similar to that of MT-III mRNA observed by in situ hybridization studies. ELISA and Northern blot analysis revealed that MT-III protein as well as mRNA levels were up-regulated in cerebrum soon after ischemic stress. Immunohistochemical analysis also demonstrated intense staining in neurons in injured brain after ischemia, which distributed in the same regions as in normal brain. These results suggest that MT-III plays an important role in protecting neurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia.

Animals↗
PubMed1997

Total parenteral nutrition alters NPY/PYY receptor levels in the rat brain.

The regulation of appetite and satiety is complex and may involve peptide mediators such as cholecystokinin (CCK) and neuropeptide Y (NPY). Studies have indicated that calories administered enterally and parenterally impact on feeding, and possibly via the release of such mediators. Recent data from our laboratory have shown that total parenteral nutrition (TPN) reduces sham feeding in dogs by 50%. We hypothesized that TPN may alter feeding via an NPY-mediated mechanism. To test our hypothesis, we examined the effect of continuous administration of TPN on NPY receptor levels in the rat brain. Rats were surgically prepared with intravenous catheters. After 72 h of TPN infusion, the rats were anesthesized with sodium pentobarbital and their brains were removed. Neuropeptide Y receptor density was assessed by autoradiography in the paraventricular nucleus, olfactory cortex, dentate gyrus, and thalamus. These results were compared to the control group receiving intravenous saline. A third group receiving enteral nutrition was examined as well. Neuropeptide Y receptor numbers were significantly increased in the paraventricular nucleus of rats receiving TPN compared to the groups receiving intravenous saline or enteral nutrition. We conclude that continuous parenteral nutrition significantly increases NPY receptor density in the rat brain suggesting that TPN may impact feeding via the regulation of NPY receptor-mediated effects.

Animals↗
PubMed1997

Behavioral and neurochemical effects induced by subchronic l-deprenyl administration.

(-)Deprenyl was administered orally to rats for 15 days. In the staircase maze, a reduction of incorrect responses was observed at 0.9 mg/kg/day; higher or lower doses (3.5 or 0.35 mg/kg/day) were ineffective. In the same range of doses, the subchronic administration of (-)deprenyl did not modify the levels of norepinephrine, 5-hydroxytryptamine, 5-hydroxyindolacetic acid or the density and affinity of alpha-noradrenergic receptors in the cortex, olfactory system, hippocampus and striatum. An increase of the dopamine and a reduction of dihydroxyphenylacetic acid levels was observed only at the highest tested doses, at which no behavioral modification was observed. Only at 1.0 mg/kg/day did (-)deprenyl increase the acetylcholine (ACh) levels in the olfactory system, hippocampus and striatum. This neurochemical effect may be correlated to the behavioral effect observed in the same range of doses. We propose that this increase of ACh levels is determined by an activation of dopaminergic systems, resulting from the increase in the levels of PE caused by the inhibition of monoamine oxidase B (MAO-B) by (-)deprenyl.

Acetylcholine↗
PubMed1998

The small-eye mutation results in abnormalities in the lateral cortical migratory stream.

Mice with homozygous mutations of the Pax-6 gene exhibit a constellation of developmental problems including the absence of eyes and nasal cavities and problems in the movement of neuroblasts out of the germinal epithelium. In this paper, we demonstrate further disturbances in neuronal migration. Normally, cells produced along the lateral ventricles move laterally across the pallium, ultimately coming to reside in the lateral neocortex and primary olfactory cortex. In mutant animals, these cells continue to migrate to the pial surface of the brain.

Animals↗
PubMed1997

Changes in the expression of novel Cdk5 activator messenger RNA (p39nck5ai mRNA) during rat brain development.

We previously reported that a neuron-specific Cdk5 activator, p35nck5ai, was most prominent in the newborn rat brain. In the adult brain, the expression decreased in most regions except hippocampus and primary olfactory cortex. A novel neuron-specific Cdk5 activator, p39nck5ai, has been recently cloned. To clarify whether two activators were differentially distributed throughout brain development, in this study, we examined the spatial and temporal expression of p39nck5ai in the development rat brain. Northern blot analysis showed that p39nck5ai expression was low in 15-day old fetuses and newborn, and was most prominent in the 1-3 week-old rat brains. In the adult rat brain, expression declined to the same level as in newborn rat brain. In situ hybridization showed that p39nck5ai mRNA was weakly expressed in all neurons of all regions in the newborn rat brain and the transcriptional level was highest in all regions in the 3 week-old rat brain. In the adult, expression was decreased in most neurons except Purkinje and granule cells in the cerebellum which retained high levels. These results suggest that p35nck5a and p39nck5ai may have different functional roles in distinct brain regions during different states of the rat brain development.

Aging↗
PubMed2000

Regional expression of a gene encoding a neuron-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain.

We have analyzed expression of a gene encoding a brain-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI), which was recently cloned from human brain, in rat forebrain using in situ hybridization. The expression of DNPI mRNA showed a widespread but highly heterogeneous pattern of distribution in the forebrain, where hybridization signals were observed in neurons but not in any other types of cells. Neurons expressing the mRNA were far more numerous in the diencephalon than in the telencephalon. In the thalamus, a number of neurons with high levels of signals were localized to all nuclei of the dorsal thalamus, habenular nuclei and subthalamic nucleus, but not the reticular nucleus and zona incerta. Moderate signal levels were seen in many neurons throughout the hypothalamus, particularly the ventromedial, paraventricular, supraoptic and arcuate nuclei, lateral hypothalamic area and mammillary complex. In contrast, expression of DNPI mRNA in the telencephalon was generally at a low level and occurred locally in some restricted regions within the neocortex, retrosplenial cortex, piriform cortex, olfactory regions, hippocampal formation and medial amygdaloid nucleus. The present results suggest that DNPI functions in heterogeneous neuron populations as a neuron-specific Na(+)-dependent inorganic phosphate cotransport system predominantly expressed in the diencephalon of the rat.

Animals↗
PubMed2001

Structure and expression of the glycine cleavage system in rat central nervous system.

The glycine cleavage system (GCS) is a mitochondrial multienzyme system consisting of four individual proteins, three specific components (P-, T-, and H-proteins) and one house-keeping enzyme, dihydrolipoamide dehydrogenase. Inherited deficiency of the GCS causes nonketotic hyperglycinemia (NKH), an inborn error of glycine metabolism. NKH is characterized by massive accumulation of glycine in serum and cerebrospinal fluids and severe neuronal dysfunction in neonates. To elucidate the neuropathogenesis of NKH, we cloned cDNAs encoding three specific components of the GCS and studied the gene expression in rat central nervous system. P-, T-, and H-protein cDNAs encoded 1024, 403, and 170 amino acids, respectively. In situ hybridization analysis revealed that P-protein mRNA was expressed mainly in glial-like cells, including Bergmann glias in the cerebellum, while T- and H-protein mRNAs were detected in both glial-like cells and neurons. T- and H-protein mRNAs, but not P-protein mRNA, were expressed in the spinal cord. Primary astrocyte cultures established from cerebral cortex had higher GCS activities than hepatocytes whereas those from spinal cord expressed only H-protein mRNA and had no enzymatic activity. An important role of glycine as inhibitory neurotransmitter has been established in the brainstem and spinal cord and another role of glycine as an excitation modulator of N-methyl-D-aspartate receptor is suggested in the hippocampus, cerebral cortex, olfactory bulbus, and cerebellum. Our results suggest that the GCS plays a major role in the forebrain and cerebellum rather than in the spinal cord, and that N-methyl-D-aspartate receptor may participate in neuropathogenesis of NKH.

Age Factors↗
PubMed1996

Distinct localization of two serine-threonine kinase receptors for activin and TGF-beta in the rat brain and down-regulation of type I activin receptor during peripheral nerve regeneration.

The localizations of serine-threonine kinase receptor mRNA for the novel type I TGF-beta and/or activin receptor named B1 (rat), ALK-4 (mouse) or ActR-IB (human) were demonstrated by in situ hybridization. As the putative ligand for this receptor in the brain has not yet been clearly determined, we compared its localization to type II activin receptor (ActR-II) which is the counterpart of the type I activin receptor. B1 mRNA was widely observed in neuronal cells throughout the brain, and especially strong positive signals were found in the cerebral cortex, olfactory tubercle, and hippocampus. The localization of B1 mRNA coincided well with that of ActR-II. This strongly suggests that B1 (ALK-4/ActR-IB) could be the type I activin receptor, as type I and type II activin receptor were supposed to form a receptor complex. In addition, we examined the localization of type II TGF-beta receptor (TbetaRII) mRNA which is an essential counterpart of the type I TGF-beta receptors for TGF-beta signaling. TbetaRII mRNA was expressed mainly in non-neuronal cells such as choroid plexus. In addition, TbetaRII mRNA expression was also found in a minor population of neuronal cells. TbetaRII mRNA-positive neurons were observed in the reticular thalamus, laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus and the ventral tegmental nucleus. The localization of TbetaRII was markedly different from that of activin receptors in the rat brain. Since TGF-betas and activins are known as growth factors and/or survival factors, we examined changes in levels of B1 and TbetaRII mRNA expression during peripheral nerve regeneration. Expression of B1 mRNA in the axotomized hypoglossal motoneurons was substantially decreased from day 3 after axotomy and this decrease was significant until postoperative day 28, whereas no TbetaRII signal was observed in hypoglossal nucleus prior or after axotomy. This transient down-regulation of B1 mRNA expression suggests that activin signaling is somehow suppressed during peripheral nerve regeneration.

Activin Receptors↗
PubMed1998

New evidence for presence of tyrosinase in substantia nigra, forebrain and midbrain.

Tyrosinase and tyrosinase-related proteins (TRP-1 and TRP-2) are essential for melanin synthesis and are expressed in neural crest-derived melanocytes and in the pigment epithelium of the retina. Recent results suggest expression of all three proteins within the central nervous system. We performed a transgenic assay using beta-galactosidase as reporter gene to monitor tyrosinase promoter activity in vivo. During embryogenesis, we found expression in several locations of developing forebrain and midbrain. Tyrosinase, TRP-1 and TRP-2 had been equally found in extracts of adult mouse brain. In adult brain, we detected tyrosinase promoter activity in cortex, olfactory system, hippocampus, epithalamus and substantia nigra, areas corresponding to positive staining during embryogenesis. Thus, tyrosinase promoter is active throughout murine brain development, and tyrosinase could be implicated in neuromelanin formation in the substantia nigra, and in neurodegenerative disorders like Parkinson's disease.

Animals↗
PubMed1998

Testosterone as well as estrogen increases serotonin2A receptor mRNA and binding site densities in the male rat brain.

Our previous findings in female rats suggest that the potent effects of sex steroids on mood and mental state may be mediated, in part, by the effect of estrogen on the 5-hydroxytryptamine2A receptor (5-HT2AR) in brain. The aim of the present study was to determine the effect of acute (approximately 32h) sex steroid manipulation on central 5-HT2AR in the adult male Wistar rat. Castration (under halothane anesthesia) decreased while testosterone or estrogen, but not 5alpha-dihydrotestosterone (5alpha-DHT), increased significantly the 5-HT2AR mRNA content in dorsal raphe nucleus and the density of 5-HT2AR binding sites in frontal, cingulate and primary olfactory cortex and nucleus accumbens. The lack of effect of 5alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5alpha-DHT, increased the density of 5-HT2AR binding sites in the caudate-putamen, a brain region where aromatase is scarce. These findings are discussed in relation to the possible role of the 5-HT2AR in depression, schizophrenia and Alzheimer's Disease.

Animals↗
PubMed2000

Direct visualization of cholecystokinin subtype2 receptors in rat central nervous system using anti-peptide antibodies.

The cholecystokinin receptor, subtype 2 (CCK(2)R), is considered, based on receptor autoradiography, to be the predominant receptor for this peptide transmitter in the mammalian central nervous system. To directly visualize the CCK(2)R we utilized a convenient and sensitive immunohistochemical procedure using antipeptide receptor antibodies raised in rabbits against unique portions of the carboxyl tail and third intracellular loop of the CCK(2)R. Antibodies were characterized by ELISA and Western blotting, and used for immunohistochemistry in rat brain sections. Studies with both antibodies revealed a widespread topographic distribution of CCK(2)R-like immunoreactivity (CCK(2)R-LI) in regions such as cortex, olfactory bulb, nucleus accumbens, septum, striatum, hippocampus, basolateral amygdala, habenula, hypothalamus, thalamus, ventral mesencephalon, inferior colliculus, parabrachial nucleus, pontine nucleus, supercolliculus, red nucleus, subcommisural and occulomotor nucleus, area postrema, solitary, olivary, cochlear, cuneate and trigeminal nuclei and spinal cord dorsal horn in agreement with the results of previous receptor autoradiography.

Amino Acid Sequence↗
PubMed1996

Regional expression of c-fos in rat brain following stimulation of the ventral tegmental area.

This study has investigated the effect of stimulating the region of origin of the mesolimbic dopaminergic system, the ventral tegmental area (VTA), with the substance P analogue DiMe-C7 on the regional expression of c-fos in the rat forebrain. We have previously shown this treatment produced a prolonged increase in blood pressure and heart rate which was mediated by both dopaminergic mechanisms and vasopressin release. Stimulation of the VTA resulted in increased levels of c-Fos immunostaining in several target regions of the mesolimbic dopaminergic system (such as the frontal cortex, olfactory tubercle, islands of Calleja and amygdala), with the notable exception of the nucleus accumbens. A marked increase in c-fos expression was also found in the supraoptic nucleus but not the paraventricular nucleus in the hypothalamus. These results support a role for a number of target areas of the mesolimbic dopaminergic system and vasopressin release in the increase in blood pressure and heart rate produced by stimulation of the VTA.

Animals↗
PubMed2000

Regulation of brain-derived neurotrophic factor messenger RNA levels in avian hypothalamic slice cultures.

Mechanisms regulating the expression of brain-derived neurotrophic factor, a member of the neurotrophin family, have been extensively studied in the rat cerebral cortex, hippocampus and cerebellum. In contrast, little is known regarding the regulation of this growth factor in the hypothalamus. Here we present an analysis of the regulation of brain-derived neurotrophic factor messenger RNA levels in chick embryo hypothalamic slice cultures following exposure to potassium chloride, glutamate agonists and sex steroids. Following a week in chemically-defined media the tissue was depolarized by exposure to 50 mM potassium chloride for 6h, resulting in a significant 4.2-fold increase in the level of brain-derived neurotrophic factor messenger RNA. This result is consistent with studies of other brain regions. Similar 6-h acute exposures of the hypothalamic cultures to 25 microM N-methyl-D-aspartic acid, 25 microM kainic acid and 25 microM alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid also significantly increased messenger RNA levels 2.5-, 2.1- and 1.4-fold, respectively. It was previously reported that brain-derived neurotrophic factor levels within the rat cerebral cortex, olfactory bulb and hippocampus are altered by exposure to 17beta-estradiol. Here we show that in hypothalamic slice cultures neither acute nor chronic treatments with 10 and 100 nM 17beta-estradiol and 10nM testosterone significantly altered the steady-state level of this growth factor. These findings show that neuronal activity, induced by glutamate agonists and potassium chloride, can regulate brain-derived neurotrophic factor messenger RNA levels within embryonic hypothalamic slice cultures. This regulation could play a critical role in the modulation of programmed cell death and synaptic maturation during development of the hypothalamus.

Animals↗
PubMed1999

Localization of a glutathione-dependent dehydroascorbate reductase within the central nervous system of the rat.

In this study, we describe for the first time the occurrence, within the central nervous system of the rat, of a dehydroascorbate reductase analogous to the one we recently described in the liver. Dehydroascorbate reductase plays a pivotal role in regenerating ascorbic acid from its oxidation product, dehydroascorbate. In a first set of experiments, we showed that a dehydroascorbate reductase activity is present in brain cytosol; immunoblotting analysis confirmed the presence of an immunoreactive cytosolic protein in selected brain areas. Immunotitration showed that approximately 65% of dehydroascorbate reductase activity of brain cytosol which was recovered in the ammonium sulphate fraction can be attributed to this enzyme. Using immunohistochemistry, we found that a variety of brain areas expresses the enzyme. Immunoreactivity was confined to the gray matter. Amongst the several brain regions, the cerebellum appears to be the most densely stained. The enzyme was also abundant in the hippocampus and the olfactory cortex. The lesion of norepinephrine terminals following systemic administration of DSP-4 markedly decreased immunoreactivity in the cerebellum. Apart from the possible co-localization of the enzyme with norepinephrine, the relative content of dehydroascorbate reductase in different brain regions might be crucial in conditioning regional sensitivity to free radical-induced brain damage. Given the scarcity of protective mechanisms demonstrated in the brain, the discovery of a new enzyme with antioxidant properties might represent a starting-point to increase our knowledge about the antioxidant mechanisms operating in several central nervous system disorders.

Animals↗
PubMed1998

Resistance of gonadotropin-releasing hormone neurons to glutamatergic neurotoxicity.

Although many studies provide evidence that glutamatergic pathways regulate the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, it is controversial as to whether they act directly upon GnRH neurons. The aim of the current study was to determine whether GnRH neurons are susceptible to the neurotoxic actions of specific glutamate agonists (N-methyl-D-aspartate [NMDA] and kainic acid), the rationale being that neurotoxic loss of GnRH neurons would provide evidence that the perikarya possess specific classes of glutamate receptor. Unilateral 1-microl injections of NMDA (12-120 mM), kainic acid (0.5-2.5 mM), or vehicle were stereotaxically directed at the preoptic area (mPOA)/diagonal band of Broca (dbB) in the region of the organum vasculosum of the lamina terminalis (OVLT) of male adult hamsters (Phodopus sungorus). The number and appearance of GnRH neurons were determined by immunocytochemistry 3-8 days later. The morphology of GnRH neurons in the vicinity of the injection sites appeared normal after both kainic acid and NMDA treatment, and there was no significant decrease in the numbers of GnRH perikarya identified following these treatments. Both agonists caused massive cellular loss when injected directly into cortical areas and striatum. In the experimental studies, there was little neuronal loss within the mPOA or dbB after either toxin, despite clear neuronal loss in areas adjacent to the injection sites, including ventral striatum and olfactory cortex. In follow-up studies, immunocytochemical and in situ hybridisation analysis of the NMDAR1 and NMDAR2 glutamate receptor subunits confirmed their widespread distribution in regions containing GnRH perikarya, but no colocalization within GnRH neurons was observed. The susceptibility of neural areas to NMDA neurotoxicity did not correlate with any difference in the regional expression of these glutamate receptor subunits. The resistance of GnRH neurons to the neurotoxic actions of two different glutamate agonists and the failure to detect colocalisation of NMDAR1 or NMDAR2 subunits within GnRH perikarya are consistent with the notion that the effects of glutamate upon GnRH secretion are not exerted directly upon GnRH cell bodies.

Animals↗
PubMed1985

Highly sensitive assay for acetylcholinesterase activity by high-performance liquid chromatography with electrochemical detection.

A highly sensitive assay for acetylcholinesterase (AChE) activity was devised by high-performance liquid chromatography with electrochemical detection. It is based on the separation of acetylcholine and choline on an octadecylsilane reversed-phase column, followed by their enzymatic conversion into hydrogen peroxide through the post-column reaction with immobilized AChE and choline oxidase. The system is highly sensitive, and the relationship between the peak height and the amount of choline is linear over the range 5 pmol to 5 nmol. When homogenate of bovine caudate nucleus was used as enzyme, the Michaelis constant of the enzyme for acetylcholine was 0.4 mM. The regional distribution of AChE activity in rat brain was examined, and the order of the activity from the highest to the lowest agreed with the reported brain distribution of AChE: striatum, thalamus plus hypothalamus, pons plus medulla oblongata, cerebral cortex, olfactory bulb, and cerebellum.

Acetylcholine↗