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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The hippocampus is an important brain structure for working and spatial memory in animals and humans, and it is also a vulnerable as well as plastic brain structure as far as sensitivity to epilepsy, ischemia, head trauma, stress, and aging. 2. The hippocampus is also a target brain area for the actions of hormones of the steroid/thyroid hormone family, which traditionally have been thought to work by regulating gene expression. "Genomic" actions of steroid hormones involve intracellular receptors, whereas "nongenomic" effects of steroids involve putative cell surface receptors. Although this distinction is valid, it does not go far enough in addressing the variety of mechanisms that steroid hormones use to produce their effects on cells. This is because cell surface receptors may signal changes in gene expression, while genomic actions sometimes affect neuronal excitability, often doing so quite rapidly. 3. Moreover, steroid hormones and neurotransmitters may operate together to produce effects, and sometimes these effects involve collaborations between groups of neurons. For example, a number of steroid actions in the hippocampus involve the coparticipation of excitatory amino acids. These interactions are evident for the regulation of synaptogenesis by estradiol in the CA1 pyramidal neurons of hippocampus and for the induction of dendritic atrophy of CA3 neurons by repeated stress as well as by glucocorticoid injections. In addition, neurogenesis in the adult and developing dentate gyrus is "contained" by adrenal steroids as well as by excitatory amino acids. In each of these three examples, NMDA receptors are involved. 4. These results not only point to a high degree of interdependency between certain neurotransmitters and the actions of steroid hormones, but also emphasize the degree to which structural plasticity is an important aspect of steroid hormone action in the adult as well as developing nervous system.
Cell Mol Neurobiol 1996 Apr
PMID:Gonadal and adrenal steroids regulate neurochemical and structural plasticity of the hippocampus via cellular mechanisms involving NMDA receptors. 874 63

The sodium channel beta 1 subunit (Na beta 1) is a component of the rat brain voltage-dependent sodium channel. We have used nonradioactive in situ hybridization cytochemical techniques to demonstrate that transcript levels of Na beta 1 are differentially upregulated during postnatal development of several CNS regions, with selective labeling of specific neuronal populations. In the hippocampus, labeling of the pyramidal cell layer (particularly in the CA3 region) and dentate granule cells was initially observed at postnatal day 2 (P2) and P10, respectively, and became progressively more intense with maturation. Labeled cells were first observed in the hilus at P10. In the developing cerebellum, transient labeling was observed in the external granule cell layer beginning at P1 while label increased in the internal granule cell layer up to P21. Purkinje cells showed significant label beginning at P4 and increasing up to P21. Weak signal was seen in neurons of deep nuclei at P1 and increased up to P21. Na beta 1 labeling in the spinal cord was first observed in the ventral horn at P2, and the intensity of labeling in these large motoneurons gradually increased. In addition, there was a ventral-dorsal gradient in this region, with label appearing subsequently in neurons of Rexed laminae IX, VII and VIII, and in the dorsal horn (Rexed laminae I-VI). In these regions, the labeling reached a plateau within the first 2-3 weeks after birth and persisted into the adult rat. The time course and regional heterogeneity of Na beta 1 expression are consistent with the hypothesis that the expression of mature Na+ channels, including Na beta 1, contributes to the development of circuitry that supports complex patterns of electrogenesis.
Brain Res Mol Brain Res 1995 Dec 28
PMID:Na+ channel beta 1 subunit mRNA expression in developing rat central nervous system. 875 Aug 27

Three days after long-term potentiation (LTP) there is a decrease in the gene expression of protein F1 (GAP-43) and gamma-PKC in CA3 pyramidal cells that is correlated with the magnitude of LTP. We predicted these decreases would be preceded by an increment in gene expression. At 1 h, but not at 2 h after LTP, F1/GAP-43 and gamma-PKC mRNA hybridization were increased, but increases were also observed after control stimulation. At both 1 and 2 h after LTP, changes in F1/GAP-43 hybridization were positively correlated with gamma-PKC hybridization and negatively correlated with LTP magnitude. These data indicate that correlated alterations in F1/GAP-43 gene expression and synaptic efficacy can occur as early as 1 h after LTP and persist for days.
Brain Res Mol Brain Res 1995 Dec 28
PMID:Protein F1/GAP-43 and PKC gene expression patterns in hippocampus are altered 1-2 h after LTP. 875 Aug 40

Chronic exposure to stress levels of corticosteroids alters many aspects of hippocampal function and may lead to neurodegeneration. Male rats were treated for 10 days with corticosterone (CORT) or vehicle pellets, and mRNA levels for six gamma-aminobutyric acid (GABAA) receptor subunits were measured. Effects of castration on subunit mRNA levels in CORT- and vehicle-treated animals were also examined. In situ hybridization studies demonstrated that mRNA levels for hippocampal GABAA receptor alpha 1, alpha 2, beta 1, beta 2, beta 3, and gamma 2 subunits were differentially altered by CORT treatment. Levels of alpha 1 and alpha 2 mRNA decreased in the dentate gyrus, and beta 1 mRNA levels decreased in CA1 and dentate gyrus of CORT-, compared to vehicle-treated, animals. In contrast, beta 2 subunit levels increased in all hippocampal regions examined, beta 3 levels increased in the dentate gyrus, and gamma 2 levels increased in CA1-CA3. The alpha 1, beta 1, and beta 2 mRNA levels all increased in the cingulate cortex of CORT-treated animals. There was no significant effect of gonadal state on any of the subunits examined, but there was a significant negative correlation between testosterone levels and mRNA levels of alpha 1, alpha 2 and beta 3 in specific regions. These data demonstrate that chronic exposure to stress levels of CORT produces complex changes in the mRNA levels of multiple GABAA receptor subunits, independently of the CORT-induced suppression of circulating testosterone.
Brain Res Mol Brain Res 1995 Dec 01
PMID:Chronic exposure to stress levels of corticosterone alters GABAA receptor subunit mRNA levels in rat hippocampus. 875 Aug 58

Injured neurons in the CNS are known to synthesize high levels of proliferation related oncogene products and heat shock proteins without dividing. Statin is a cell cycle regulated nuclear phosphoprotein, selectively associated with the non-proliferative state in a wide variety of cell types. In the present study, neuronal statin was examined following lethal or sublethal neuronal injuries in the hippocampus of Alzheimer's disease patients, in rats receiving kainate lesions to the dorsal hippocampus and in entorhinal cortex lesioned rats. Immunolabelling of nuclear statin showed that statin immunoreactivity increased preferentially in CA1 pyramidal neurons of the hippocampus in Alzheimer's disease. In kainate lesioned rats, statin immunoreactivity was markedly induced in the CA3 hippocampal region in association with neuronal loss. Entorhinal cortex lesioned rats showed a transient induction of statin between 2 and 6 days post lesion in CA1 neurons. However, cell counts in entorhinal cortex lesioned rats remained unaltered in the CA1 and granule cell layers during the entire 30 day time course, indicating that increased statin levels are not secondary to neuronal degeneration and are not necessarily accompanied by irreversible neuronal death. It is concluded that, in addition to proliferation related gene products, neuronal injury induces an increase in levels of statin, a nuclear marker of cell cycle arrest. Furthermore, statin may be a potentially useful marker of injurious neuronal stress, even under conditions that do not necessarily lead to irreversible cell death.
Brain Res Mol Brain Res 1995 Dec 01
PMID:Increased levels of statin, a marker of cell cycle arrest, in response to hippocampal neuronal injury. 875 Aug 61

The purpose of the present study was to determine if gonadal steroids can alter the amounts of GnRH receptor mRNA in the pyramidal and granule neurons of the hippocampus of female and male rats and if GnRH causes a change in the production of inositol phosphates in hippocampal slices in vitro. The results show that in the ovariectomized rat the amount of GnRH receptor mRNA is increased to 137% in area CA1 and to 147% in area CA3 and in the dentate gyrus when compared to the ovariectomized, estradiol-progesterone treated animal. Similarly, in the orchidectomized male rat the amount of GnRH receptor mRNA is increased to 155% in area CA1, to 146% in area CA3 and to 145% in the dentate gyrus when compared to the intact male rat. There was no significant difference in the relative amounts of GnRH receptor mRNA when gonadectomized male and female rats were compared. Addition of GnRH (100 pM-1 microM) to hippocampal slices in vitro caused a dose-dependent increase in the production of [3H]inositol phosphate which was abolished by co-administration of a GnRH antagonist. The increase in inositol phosphate production was significantly higher at low doses of GnRH (100 pM-1 nM) in estradiol-progesterone treated female and in intact male rats when compared to gonadectomized rats. The results suggest that the amount of GnRH receptor mRNA in the hippocampus is at least in part regulated by gonadal steroids and that the steroid hormones can sensitize the GnRH target neurons to respond more robustly to a GnRH stimulus.
Brain Res Mol Brain Res 1995 Oct
PMID:Regulation of hippocampal gonadotropin releasing hormone (GnRH) receptor mRNA and GnRH-stimulated inositol phosphate production by gonadal steroid hormones. 877 51

The distribution of messenger ribonucleic acids (mRNA) for serotonin (5-HT) receptors of 1A, 2A and 1D alpha type (5-HT1A, 5-HT2A, and 5-HT1D alpha) was examined and compared in autoptic human brain by means of in-situ hybridization using cRNA probes, in those areas with the highest density of the receptors, as observed with binding techniques. The results showed that the 5-HT1A receptor mRNA was abundantly expressed in the layers II-VI of all cortical areas under examination, but the highest expression was found in the hippocampus, particularly in the granular cells of the dentate gyrus and in the pyramidal cell layer of the Hammon's horn. The 5-HT2A receptor mRNA was mainly present in the layers III-V of the cortex, with regional differences which were particularly marked in the striate area where the layer IV was specifically labeled. On the other hand, in the hippocampus, 5-HT2A receptor mRNA was restricted to the pyramidal cell layer of the CA1 field of the Hammon's horn. No expression of both 5-HT2A and 5-HT1D alpha receptors was detected in the caudate nucleus and in putamen where only a light labeling by means of the 5-HT1A receptor probe was detected. The 5-HT1D alpha receptor mRNA was found only in the CA3 field of the Hammon's horn. These findings confirm that 5-HT receptors are widely distributed in the brain, but that the different subtypes possess a selective localization in different neuronal populations which, in turn, may express one or more receptors. The regional differences may represent the anatomical substrate of different serotonergic functions and dysfunctions.
Brain Res Mol Brain Res 1996 Jul
PMID:Comparative anatomical distribution of serotonin 1A, 1D alpha and 2A receptor mRNAs in human brain postmortem. 880 30

To determine if impaired energy metabolism might contribute to some aspects of Alzheimer disease (AD), including the vulnerability of the CA1 region of the hippocampal formation and the altered cytoskeleton evident in neurofibrillary tangles, we examined the effects of metabolic poisons on neuronal damage and cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death, particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but sparing of axonal gamma. MK-801 (a noncompetitive NMDA receptor antagonist) did not atentuate the lesions produced by intrahippocampal injection of malonate. MK-801, however, was effective against intrastriatal malonate. Acute systemic 3-NP resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but sparing of gamma. The neuronal loss in CA1 was delayed as compared to striatum. Chronic intraventricular infusion of 3-NP produced a different pattern of neuronal damage. Loss of gamma-1 immuno-reactivity was observed in CA3 and CA1 s. orients, whereas MAP2 immunostaining was preserved. These results demonstrate that chronic and acute administration of metabolic inhibitors produce distinct patterns of neuronal damage and cytoskeletal disruption. The results further suggest a differential involvement of the NMDA receptor in malonate-induced neuronal damage in striatum as compared to the hippocampus. The pattern of neuronal damage and cytoskeletal disruption observed following acute metabolic impairment resembled some aspects of neurofibrillary pathology in AD, but did not result in gamma hyperphosphorylation.
Mol Chem Neuropathol
PMID:Hippocampal damage and cytoskeletal disruption resulting from impaired energy metabolism. Implications for Alzheimer disease. 887 43

We began these experiments as an attempt to replicate in the mouse the induction by kainate (KA) of F1/GAP-43 mRNA we observed in adult rat hippocampal granule cells [Mol. Brain Res., 33 (1995) 22-28]. However, even though KA induced behavioral seizures in the mouse similar to those in the rat, neither induction of F1/GAP-43 mRNA nor subsequent mossy fiber sprouting observed in the rat was detected in three different mouse strains. It was also surprising that the distribution of constitutive levels of F1/GAP-43 mRNA in mouse and rat hippocampus was qualitatively different. Indeed, F1/GAP-43 expression in CA3 pyramidal cells was significantly greater in rat than mouse, while F1/GAP-43 expression in CA1 cells of rat and mouse was equivalent using densitometric analysis. Thus, F1/GAP-43 expression in rat is quantitatively higher in CA3 and CA1 pyramidal cells. In mouse, expression was equivalent in these two subfields. In a transgenic mouse bearing a rat F1/GAP-43 promoter-reporter (lacZ) construct (line 252), in-vivo promoter activity of F1/GAP-43 was studied in hippocampal cells. Transgene expression in hippocampal pyramidal subfields, high in CA3, low in CA1 pyramidal cells, paralleled the distribution of rat F1/GAP-43 mRNA levels, not mouse. Differences in the constitutive F1/GAP-43 expression pattern in hippocampus between rat and mouse may therefore be determined by different recognition elements present on the F1/GAP-43 promoter. KA injected into the line 252 transgenic mouse did not activate the rat F1/GAP-43 promoter in mouse hippocampal granule cells. The absence of both F1/GAP-43 mRNA expression induction and promoter activation in mouse granule cells after KA is likely related to genera differences in transcriptional regulatory mechanisms, though post-transcriptional mechanisms cannot be excluded. Since the different hippocampal chemistry of F1/GAP-43 in rat and mouse likely extends to other molecular species, behaviors in rat and mouse that depend on hippocampal function might be different as well. We therefore evaluated spatial memory ability in a delayed matching-to-sample task. In contrast to rat, we were surprised to find no evidence of the ability to learn this task in three different mouse strains. Since interest in mouse genetics in relation to behavior and memory functions of hippocampus is growing, generalizations concerning hippocampal function from studies carried out on the mouse need to be made with caution considering the specific behavioral, pharmacological, and general molecular differences observed here. One can also be opportunistic and exploit the natural variations between these two genera to gain insight into the molecular mechanisms underlying information storage.
Brain Res Mol Brain Res 1996 Sep 01
PMID:Distinctions between hippocampus of mouse and rat: protein F1/GAP-43 gene expression, promoter activity, and spatial memory. 887 1

Growth factors belonging to the TGF beta superfamily bind to and signal through a receptor complex comprising two transmembrane serine/threonine kinases, called type I and type II. Each receptor is responsible for the signaling of the individual TGF beta superfamily members. So far, five type II and six type I receptors have been cloned from mammalian sources. We report here the molecular cloning of a novel type I receptor serine/threonine kinase, ALK7 (activin receptor-like kinase 7), from rat brain. ALK7 shows a significant sequence similarity with TGF beta RI and ActRIB in the intracellular kinase domain and is quite distinct from other type I receptors in the extracellular domain. ALK7 mRNA is expressed in embryonic and in adult rat brain, where it was localized in superficial layers of the forebrain, the CA3 pyramidal subfield of hippocampus, the basal ganglia, the thalamus, and the cerebellar cortex. The functionality of the receptor was demonstrated by the identification of a constitutively active point mutant of ALK7 that activates the TGF beta/activin-responsive reporter without any ligand stimulation. Although the endogenous ligand for ALK7 has yet to be identified, its extensive anatomic distribution in brain, gut, spleen, and lung suggests important roles for this orphan receptor.
Mol Cell Neurosci 1996 Jun
PMID:Molecular cloning of a novel type I receptor serine/threonine kinase for the TGF beta superfamily from rat brain. 887 30


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