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 1,135 records · Page 63Linked to original sources
PubMed1997

Detection of Borna disease virus genome in normal human brain tissue.

Borna disease virus (BDV), a neurotropic virus naturally infecting horses and sheep, has been suggested to be associated with human psychiatric disorders. Thus far no extensive studies have been done, providing the evidence of BDV genome in normal human brain tissue. We therefore examined four brain regions of 30 normal autopsy brains for BDV p24 genome. By highly sensitive nested reverse transcriptase (RT)-mediated PCR analysis, we found positive PCR products in two brains: one in frontal and temporal cortices and hippocampus and another in frontal cortex and olfactory bulb. Our results suggest that BDV can infect human brain tissue latently, without causing an apparent neuropsychiatric disorder.

Adult↗
PubMed1997

The anticonvulsant properties of antisense c-fos oligodeoxynucleotides in kainic acid-induced seizures.

Evidence has accumulated that the immediate early gene c-fos has important physiological and pharmacological properties in the central nervous system. The role of c-fos in seizures and, in particular, kainic acid-induced seizures, is unclear. It is unknown if c-fos stimulation after kainic acid is a consequence of neuronal activation, or an intrinsic critical component of the metabolic pathways leading to seizure. To elucidate this problem we have pretreated male Wistar rats with antisense c-fos and nonsense c-fos oligodeoxynucleotides 12 h prior to kainic acid 10 mg/kg intraperitoneal. Antisense c-fos inhibited the number of wet dog shakes and the appearance of limbic motor seizures, effects not seen with nonsense or vehicle. The anticonvulsant effects were associated with reduction of both Fos and NGFI-A immunoreactivity and neuroprotection in the hippocampus, thalamus and primary olfactory cortex-amygdaloid region. Four days after antisense c-fos limbic motor seizures were not inhibited, and there was no decrease in Fos or NGFI-A immunoreactivity and no neuroprotection, indicating that the anticonvulsant effects were not secondary to a toxic effect. Sense oligonucleotides had no anticonvulsant effects when given 12 h prior to kainic acid and did not influence immunoreactivity or neuronal survival. In conclusion, these findings suggest a role for c-fos in the generation of kainic acid-induced limbic seizures and neuronal death.

Animals↗
PubMed1998

The neuroprotective effects of the recombinant interleukin-1 receptor antagonist rhIL-1ra after excitotoxic stimulation with kainic acid and its relationship to the amyloid precursor protein gene.

The cytokine interleukin-1 (IL-1) and its endogenous antagonist (IL-1ra) have important functions in the central nervous system. Recent experimental observations have suggested that recombinant IL-1RA (rhIL-1ra) has neuroprotective properties in ischaemia, excitotoxicity, and trauma. We wished to see what effect rhIL-1ra had on kainic acid-induced neuronal death and to investigate how this might relate to changes in expression of the amyloid precursor protein gene (APP) and glial fibrillary acid protein (GFAP) using in situ hybridization. Wistar rats were treated by intracerebroventricular administration with rhIL-1ra at doses of 10, 20 and 40 microg given 10 min before and 10 min after intraperitoneal kainic acid 10 mg/kg. Behaviour was measured and, after 10 days, the brains were removed for histology and in situ hybridization. There were no anticonvulsant effects on kainic acid-induced wet dog shakes or limbic motor seizures. There were no differences in the effects of rhIL-1ra at all doses tested on hippocampal temperature, blood pressure, blood gases, pH, and glucose in comparison to control. With rhIL-1ra 10 microg given twice, there was significant protection of neurons in the CA1 and CA3 field of the hippocampus and dorsal thalamus, but not in the primary olfactory cortex-amygdaloid region. Small, but insignificant, neuroprotective effects were observed in the same anatomical regions with a dose of 20 microg given twice, and no neuroprotective effects were observed with 40 microg. The enhanced neuronal survival in CA1, CA3 and the dorsal thalamus was associated with preservation of APP 695 mRNA (neuronal form) and lack of stimulation of APP 770 (glial form) and GFAP messages. Where there was no neuroprotection APP 695 mRNA was reduced and stimulation of both APP 770 and GFAP mRNAs was observed. In conclusion, rhIL-1ra has dose- and region-dependent effects on neuronal survival after kainic acid and prevents damage-induced changes in APP and GFAP mRNAs.

Amyloid beta-Protein Precursor↗
PubMed2001

Regional expression of the splice variants of Kv4.3 in rat brain and effects of C-terminus deletion on expressed K+ currents.

In situ hybridization and RT-PCR analyses have revealed that, among three Kv4.3 splice variants (a, b, and c) with distinct C-terminal cytoplasmic domains, the mRNA for Kv4.3a is abundant in cerebral cortex, cerebellum, olfactory bulb, and medulla oblongata, whereas the mRNA for Kv4.3c is localized mainly to hippocampus. Three new distinct splice variants of Kv4.3 (Kv4.3d, e and f), which consist of 601, 635, and 628 amino acids, respectively, and have distinct C-terminal cytoplasmic domains, were isolated from rat brain by RT-PCR. Kv4.3b, d, e and f were expressed at much lower levels in brain. Mutagenesis which removed 149 amino acids in C-terminal domain of Kv4.3a significantly slowed its rate of recovery from inactivation as measured in heterologous expression in HEK293 cells. Surprisingly, however, neither the rate of inactivation nor voltage dependence of the activation and inactivation were changed.

Amino Acid Sequence↗
PubMed1997

Transient gene transfer to neurons and glia: analysis of adenoviral vector performance in the CNS and PNS.

In this paper a detailed protocol is presented for neuroscientists planning to start work on first generation recombinant adenoviral vectors as gene transfer agents for the nervous system. The performance of a prototype adenoviral vector encoding the bacterial lacZ gene as a reporter was studied, following direct injection in several regions of the central and peripheral nervous system. The distribution of the cells expressing the transgene appears to be determined by natural anatomical boundaries and possibly by the degree of myelinization of a particular brain region. In highly myelinated areas with a compact cellular structure (e.g. the cortex and olfactory bulb) the spread of the viral vector is limited to the region close to the injection needle, while in areas with a laminar structure (e.g. the hippocampus and the eye) more widespread transgene expression is observed. Retrograde transport of the viral vector may serve as an attractive alternative route of transgene delivery. A time course of expression of beta-galactosidase in neural cells in the facial nucleus revealed high expression during the first week after AdLacZ injection. However, a significant decline in transgene expression during the second and third week was observed. This may be caused by an immune response against the transduced cells or by silencing of the cytomegalovirus promoter used to drive transgene expression. Taken together, the data underscore that for each application of adenoviral vectors as gene transfer agents in the nervous system it is important to examine vector spread in and infectability of the neural structure that is subject to genetic modification.

Adenoviruses, Human↗
PubMed2000

GFP-tagged expression and immunohistochemical studies to determine the subcellular localization of the tubby gene family members.

The tubby gene family consists of four members, TUB, TULP1, TULP2 and TULP3, with unknown function. However, a splice junction mutation within the mouse tub gene leads to retinal and cochlear degeneration, as well as maturity onset obesity and insulin resistance. Mutations within human TULP1 have also been shown to co-segregate in several cases of autosomal recessive retinitis pigmentosa (RP) and TULP1 deficiency in mice leads to retinal degeneration. The primary amino acid sequences of the tubby family members do not predict a likely biochemical function. As a first step in defining their function, we present a detailed characterization of the cellular and subcellular localization of the human (TUB) and mouse (tub) homologous gene products. We report the isolation of TUB splice variants which have different subcellular localizations (nuclear versus cytoplasmic) and which define a nuclear localization signal. In addition, using green fluorescent protein (GFP) tags, we observe a nuclear localization for TULP1, similar to TUB splicing forms TUB 561 and TUB 506. Finally, we report tubby expression in mouse brain by in situ hybridization and by immunohistochemistry with polyclonal antibodies. Protein was found in both the hypothalamic satiety centers and in a variety of other CNS structures including the cortex, cerebellum, olfactory bulb and hippocampus. Both nuclear and cytoplasmic signals were detected with a series of independently generated polyclonal antibodies, consistent with the presence of multiple alternatively spliced isoforms within the CNS.

Adaptor Proteins, Signal Transducing↗
PubMed1996

The expression of MEF2 genes is implicated in CNS neuronal differentiation.

The myocyte enhancer factor-2 (MEF2) proteins are transcription factors required for muscle differentiation. In the present study we examined MEF2 expression in developing cerebellar granule neurons. In the developing postnatal cerebellum, RNA blot analysis revealed that MEF2A and MEF2D RNA levels increase after birth. The majority of this increase occurs around postnatal day 9 reaching a peak at postnatal day 15-18 which is maintained in adults. This time course of expression coincides with the expression of GABA(A) receptor alpha6 subunit RNA, a marker for the differentiation of the mature cerebellar granule neurons. We further observed, using the polyclonal antibody generated against an MEF2A peptide, that MEF2 protein expression occurs primarily in the internal granule cell layer of the developing cerebellum. Thus, MEF2 expression increases as granule neurons differentiate and mature. Experiments also indicated that MEF2 expression not only occurs in the cerebellum but also in other regions of the CNS. In adult mice, expression of RNA for the MEF2 isoforms A, C and D occurs throughout the CNS. MEF2A and D expression occurs at highest levels in the olfactory bulb, hippocampus and cerebellum. The expression of MEF2C differs with low levels of expression in the cerebellum and hindbrain. Using the MEF2A polyclonal antibody, we observed a similar adult pattern of expression for the MEF2 protein with high level of expression in the olfactory bulb, cortex, hippocampus, thalamus and cerebellum. These observations suggest that MEF2 molecules may be an important factor involved in CNS neuron differentiation similar to their role in muscle differentiation.

Amino Acid Sequence↗
PubMed1997

Induction of protein tyrosine phosphatase epsilon transcripts during NGF-induced neuronal differentiation of PC12D cells and during the development of the cerebellum.

We have investigated a possible role played by protein tyrosine phosphatase epsilon (PTPepsilon), which was recently cloned and predominantly expressed in brain, in neural differentiation and function. During neuronal cell differentiation of PC12D cells triggered by NGF or FGF, PTPepsilon transcripts were transiently induced at a time between the appearance of transcripts for immediate-early genes and for neuronal cell-specific markers. PTPepsilon was the only PTPase whose transcripts were induced during PC12D cell differentiation among over two dozen PTPase transcripts so far examined. Moreover, in situ hybridization revealed that PTPepsilon transcripts were detected in the neural tube of day 12 postcoitum embryo, and in the nervous system including brain, spinal cord, and ganglions in a ubiquitous manner in late gestational stages. In 4-day-old neonatal mice, the transcripts were widely distributed in the central nervous system where the strongest expression was detected in the hippocampus, cerebral cortex, and olfactory bulb. Interestingly, in day 7 and 16 neonatal brains, the strongest PTPepsilon gene expression was localized in the granular cells of cerebellum, which might indicate that PTPepsilon is involved in the differentiation of the granular cells. The biological significance of PTPepsilon in neuronal differentiation and brain functions is discussed.

Animals↗
PubMed1998

Identification and characterization of RPTP rho, a novel RPTP mu/kappa-like receptor protein tyrosine phosphatase whose expression is restricted to the central nervous system.

We describe the cloning, chromosomal localization and characterization of RPTPrho, a new member of the RPTPmu/kappa phosphatase subfamily. Receptor tyrosine phosphatases in this subfamily are comprised of a MAM domain near the N-terminal, an immunoglobulin-like domain, four fibronectin type III repeats, a single transmembrane domain, and a large juxtamembrane segment followed by two intracellular phosphatase domains. An alternatively spliced mini-exon was identified in the extracellular segment of RPTPrho, between the fourth fibronectin type III repeat and the transmembrane domain. The RPTPrho gene was mapped to human chromosome 20 and mouse chromosome 2. Northern blot analysis demonstrated that RPTPrho expression was restricted to the central nervous system, and in situ hybridization studies showed that the RPTPrho transcript was distributed throughout the murine brain and spinal cord. Exceptionally high levels of the transcript were present in the cortex and olfactory bulbs during perinatal development, but were down-regulated during postnatal week two. The motifs found in the extracellular segment of type II receptor protein tyrosine phosphatases are commonly found in neural cell adhesion molecules, suggesting that RPTPrho may be involved in both signal transduction and cellular adhesion in the central nervous system.

Adult↗
PubMed1997

The cholinergic system in Alzheimer's disease.

The past decade has witnessed an enormous increase in our knowledge of the variety and complexity of neuropathological and neurochemical changes in Alzheimer's disease. Although the disease is characterized by multiple deficits of neurotransmitters in the brain, this overview emphasizes the structural and neurochemical localization of the elements of the acetylcholine system (choline acetyltransferase, acetylcholinesterase, and muscarinic and nicotinic acetylcholine receptors) in the non-demented brain and in Alzheimer's disease brain samples. The results demonstrate a great variation in the distribution of acetylcholinesterase, choline acetyltransferase, and the nicotinic and muscarinic acetylcholine receptors in the different brain areas, nuclei and subnuclei. When stratification is present in certain brain regions (olfactory bulb, cortex, hippocampus, etc.), differences can be detected as regards the laminar distribution of the elements of the acetylcholine system. Alzheimer's disease involves a substantial loss of the elements of the cholinergic system. There is evidence that the most affected areas include the cortex, the entorhinal area, the hippocampus, the ventral striatum and the basal part of the forebrain. Other brain areas are less affected. The fact that the acetylcholine system, which plays a significant role in the memory function, is seriously impaired in Alzheimer's disease has accelerated work on the development of new drugs for treatment of the disease of the 20th century.

Acetylcholinesterase↗
PubMed2001

Purification, characterization and developmental expression of rat brain PSP protein.

We have isolated a perchloric acid-soluble protein designated as B-PSP1 from the postmitochondria supernatant fraction of rat brain. It was purified by gel filtration and anti-PSP1 affinity chromatography. Immunoblotting, peptide mapping, partial amino acid sequencing and reverse transcriptase-polymerase chain reaction showed that the amino acid sequence of B-PSP1 was identical with that of PSP isolated from rat liver. B-PSP1 was expressed in all regions including frontal cortex, posterior cortex, cerebellum, hippocampus, olfactory bulb, striatum, thalamus, midbrain, entorhinal cortex, pons, medulla and spinal cord. Immunohistochemical study showed that the expression of B-PSP1 was observed in ependymal cells of choroid plexus and glial cells of the other region. The expression of B-PSP1 in brain increased gradually from the first day to the 60th day of postnatal age, but the expression of B-PSP1 was slower than that of GFAP which is a marker protein of glial cells. The expression of PSP may be related to the cellular function rather than the developmental regulation of the glial cells. Thus, our findings are the first report on the presence of a PSP in rat brain which may be involved in the regulation of cellular function.

Animals↗
PubMed2001

Dystroglycan distribution in adult mouse brain: a light and electron microscopy study.

Dystroglycan, originally identified in muscle as a component of the dystrophin-associated glycoprotein complex, is a ubiquitously expressed cell-surface receptor that forms a transmembrane link between the extracellular matrix and the cytoskeleton. It contains two subunits, alpha and beta, formed by proteolytic cleavage of a common precursor. In the brain, different neuronal subtypes and glial cells may express dystroglycan in complex with distinct cytoplasmic proteins such as dystrophin, utrophin and their truncated forms. To examine the distribution of dystroglycan in adult mouse brain, we raised antibodies against the recombinant amino- and carboxyl-terminal domains of alpha-dystroglycan. On western blot, the antibodies recognized specifically alpha-dystroglycan in cerebellar extracts. Using light microscopy, alpha-dystroglycan was found in neurons of the cerebral cortex, hippocampus, olfactory bulb, basal ganglia, thalamus, hypothalamus, brainstem and cerebellum, where dystrophin and its truncated isoforms are also known to be present. Electron microscopy revealed that alpha-dystroglycan immunoreactivity was preferentially associated with the postsynaptic specializations. Dystroglycan immunostaining was also detected in perivascular astrocytes and in those facing the pia mater, where utrophin and dystrophin truncated isoforms are present. The cell body and endfeet of astrocytes around blood vessels and the endothelial cells at the blood-brain barrier also expressed dystroglycan. From these data, we suggest that dystroglycan, by bridging the extracellular matrix and the cytoskeleton, may play an important functional role at specialized intercellular contacts, synapses and the blood-brain barrier, whose structural and functional organization strictly depend on the integrity of the extracellular matrix-cytoskeleton linkage.

Animals↗
PubMed2003

Distribution of the rhythm-related genes rPERIOD1, rPERIOD2, and rCLOCK, in the rat brain.

High densities of mRNAs for three rhythm-related genes, rPeriod1 (rPer1), rPer2, and rClock, which share high homology in Drosophila and mice, were found in the hypothalamic suprachiasmatic nucleus (SCN). The SCN, however, is not the only brain region that expresses these genes. To understand the distributions and possible physiological roles of these rhythm-related genes, we examined the gene expressions of rPer1, rPer2, and rClock in different brain regions by serial coronal, sagittal, and horizontal brain sections in Sprague-Dawley male rats. Animals were housed in a light-controlled room (lights on from 0600 to 1800 h) and killed at 1000 or 1200 h, which corresponds to Zeitgeber time 4 or 6. Semi-quantitative in situ hybridization with (35)S-riboprobes was used to evaluate mRNA levels. The mRNAs of rPer1, rPer2, and rClock were widely distributed in the rat CNS, including the olfactory bulb, cortex, piriform cortex, SCN, ventromedial hypothalamus, arcuate nucleus, hippocampus, mammillary nucleus, pontine nucleus, superior and inferior colliculus, cerebellum, median eminence/pars tuberalis, pineal gland, and pituitary. The expression patterns of mRNAs for rPer1 and rPer2 were almost identical. In contrast, different expression patterns were observed between rClock and rPer1 or rPer2 in several brain regions, including the hypothalamic supraoptic and suprachiasmatic nuclei, the paraventricular zone of the caudate putamen, the superior olivary nucleus, and anterior and intermediate lobes of the pituitary. These findings suggest that the different expression patterns observed for rPer1, rPer2, and rClock might be due to their different physiological role(s) in those brain regions.

Animals↗
PubMed2003

Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation.

Cytochrome oxidase activity was examined in a transgenic mouse model of Alzheimer's disease with overexpression of the 751 amino acid isoform of beta-amyloid precursor protein with the Swedish mutation under control of the murine thy-1 promoter. The neuritic plaques, abundantly localized in the hippocampus and anterior neocortical areas, showed a core devoid of enzymatic activity surrounded by higher cytochrome oxidase activity at the sites of the dystrophic neurites and activated glial cells. Quantitative measures, taken only in the healthy-appearing regional areas without neuritic plaques, were higher in numerous limbic and non-limbic regions of transgenic mice in comparison with controls. Enzymatic activity was higher in the dentate gyrus and CA2-CA3 region of the hippocampus, the anterior cingulate and primary visual cortex, two olfactory structures, the ventral part of the neostriatum, the parafascicularis nucleus of the thalamus, and the subthalamic nucleus. Brainstem regions anatomically related with altered forebrain regions were more heavily labeled as well, including the substantia nigra, the periaqueductal gray, the superior colliculus, the medial raphe, the locus coeruleus and the adjacent parabrachial nucleus, as well as the pontine nuclei, red nucleus, and trigeminal motor nucleus. Functional brain organization is discussed in the context of Alzheimer's disease. Although hypometabolism is generally observed in this pathology, the increased cytochrome oxidase activity obtained in these transgenic mice can be the result of a functional compensation on the surviving neurons, or of an early mitochondrial alteration related to increased oxidative damage.

Alzheimer Disease↗
PubMed1999

Localization of the Norrie disease gene mRNA by in situ hybridization.

Norrie disease is a rare X-linked recessive neurodevelopmental disorder. The affected males manifest congenital blindness, which is often associated with hearing loss, mental retardation and psychiatric problems. Genetic linkage studies have localized the gene to the short arm of the X-chromosome and the gene has been isolated recently. The encoded protein is a member of the superfamily of growth factors containing a cystine knot motif and may be involved in cell adhesion and neurodevelopment. Molecular genetic analysis revealed a large number of missense, nonsense, deletion, and splice-site mutations among Norrie patients. In order to further determine the role of the Norrie disease gene, we studied the distribution pattern of its mRNA in the retina and in brain by in situ hybridization. The results show abundant hybridization signals in outer nuclear, inner nuclear, and ganglion cell layers of the retina in all three species (mice, rabbit, and human) examined. There was no significant expression in the vitreous body, lens, and rod outer segment. High expression levels were also observed in the cerebellar granular layer, hippocampus, olfactory bulb, cortex, and epithelium of the rabbit brain. These data suggest that the Norrie disease gene could play a critical role in the differentiation or maintenance of the differentiated state of the retina.

Animals↗
PubMed2000

Comparative neurobiological effects of ibogaine and MK-801 in rats.

Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties. Although ibogaine binds to multiple targets in the brain, recent evidence suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK-801. The purpose of the present study was to compare neurochemical and neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of rats (N=6-8/group) were decapitated 30 or 60 min after injection. Brains were harvested for analysis of dopamine (DA) and its metabolites, while trunk blood was collected for analysis of plasma corticosterone and prolactin. Ibogaine produced marked dose-dependent reductions in tissue DA with concurrent increases in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently observed in the cortex, striatum, olfactory tubercle, and hypothalamus. MK-801, on the other hand, did not reduce DA levels in any brain region but did cause modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused comparable elevations in circulating corticosterone, but only ibogaine increased prolactin. The present findings show that the effects of ibogaine on DA neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801. Thus, the wide spectrum of in vivo actions of ibogaine can probably not be explained simply on the basis of antagonism at NMDA receptors.

Animals↗
PubMed2000

Formin-2, a novel formin homology protein of the cappuccino subfamily, is highly expressed in the developing and adult central nervous system.

Formin-1 is the founding member of a family of genes of emerging biological and medical importance that share specific domains of homology, allowing them to be classified together as the formin homology proteins. Although deficiency mutations in formin-1 lead to profound developmental defects in limb and kidney formation, similar deficiency mutations in more distantly related members of this family (diaphanous and cappuccino in Drosophila and BNI1 in yeast) have ostensibly unrelated phenotypes. Here we describe murine and human formin-2 (Fmn2), a gene which bears a high degree of similarity to formin-1 and cappuccino. The mouse gene, which encodes a putative 1567-amino-acid open reading frame and maps to mouse Chromosome 1, is expressed almost exclusively in the developing and mature central nervous system. Expression begins at embryonic day 9. 5 in the developing spinal cord and brain structures and continues in neonatal and adult brain structures including the olfactory bulb, cortex, thalamus, hypothalamus, hippocampus and cerebellum. Human formin-2 has a similar expression pattern.

Adult↗