Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.26.9 (ribonuclease)
6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several reports indicate that Alzheimer disease (AD) brain contains elevated levels of heat shock 70 proteins. To determine the cellular localization of the heat shock 70 mRNAs, specific oligonucleotide probes were in situ hybridized to AD and control brains. When oligonucleotides were in situ hybridized to brain sections with no AD neuropathology, hybridization was cell-specific and prior ribonuclease (RNase) treatment of adjacent sections resulted in no hybridization signal. However, in situ hybridization to AD hippocampus resulted in heavy grain deposition over senile plaques and neurofibrillary tangles. Despite altering a number of experimental variables, we observed a similar pattern of grain deposition with most of the oligonucleotides tested, including one oligonucleotide specific for glutamic acid decarboxylase mRNA. In situ hybridization with either an RNA probe for glutamic acid decarboxylase or an oligonucleotide probe specific for 18S rRNA did not show this pattern of grain deposition. In control studies a sense hsc70 oligonucleotide showed no grain deposition in either cerebellum or hippocampus. Sections from AD hippocampus pretreated with RNase prior to in situ hybridization demonstrated enhanced grain deposition with the majority of probes tested. Anomalous in situ hybridization to AD hippocampus was usually eliminated by removing formamide from the posthybridization washes, although post-RNase sticking often remained intense. These findings indicate that artifactual probe binding to senile plaques and neurofibrillary tangles may complicate the analysis of in situ hybridization studies using oligonucleotide probes to determine mRNA distribution in AD brain.
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PMID:Anomalous binding of radiolabeled oligonucleotide probes to plaques and tangles in Alzheimer disease hippocampus. 791 65

gamma-Aminobutyric acid (GABA)ergic neurons terminating in the rostral hypothalamus are stimulated by testosterone. To investigate whether this action is mediated locally through androgen receptors in the rostral hypothalamus, bilateral microcannulas (28 gauge) containing the androgen receptor antagonist, hydroxyflutamide (HF), were stereotaxically implanted into the rostral medial preoptic area (rMPA) just dorsal to the major population of GnRH cell bodies. Two days later, blood samples were collected for assay of LH, and animals were killed for determination of GABAergic neuronal activity in tissue dissected from the site of the implanted cannulas. Animals were decapitated either without treatment or 60 min after inhibition of GABA degradation by aminooxyacetic acid (100 mg/kg, ip). The rate of GABA accumulation in the tissue after aminooxyacetic acid treatment was used as a measure of GABA turnover. Levels of messenger RNA for both forms of glutamic acid decarboxylase (GAD65 and GAD67), the rate-limiting enzyme responsible for GABA synthesis also were measured by a microlysate ribonuclease protection assay. LH levels were significantly increased (1.8-fold) in HF-treated animals compared with controls. In the MPA, beneath the implant cannulas, GABA turnover was significantly reduced in HF-treated rats. There was no effect of treatment in the frontal cortex, which was used as a control region. Surprisingly, levels of messenger RNA for both GAD65 and GAD67 were significantly increased in HF-treated rats. The results indicate that GABAergic neurons terminating in the rostral hypothalamus are tonically stimulated by testosterone acting by means of androgen receptors localized in this region. These findings support the working hypothesis that androgen-sensitive GABAergic neurons in the rMPA mediate the negative feedback action of testosterone on GnRH secretion in the male rat.
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PMID:Antiandrogen microimplants into the rostral medial preoptic area decrease gamma-aminobutyric acidergic neuronal activity and increase luteinizing hormone secretion in the intact male rat. 882 73

There is considerable evidence that GABAergic neurons play an important role in the regulation of gonadotropin-releasing hormone (GnRH) secretion, and that these neurons may mediate the feedback actions of gonadal steroids on GnRH neurons. The aim of the present study was to investigate whether endogenous changes in ovarian steroid secretion during the estrous cycle influenced GABAergic neuronal activity in the preoptic region of the hypothalamus, and in other steroid-sensitive brain regions. Intact, adult female rats were sacrificed at various times during the days of metestrus or proestrus. GABAergic neuronal activity was estimated by measuring the rate of accumulation of GABA in microdissected brain regions after pharmacological inhibition of GABA degradation. Concentrations of mRNA for both forms of glutamic acid decarboxylase (GAD65 and GAD67) were quantified in microdissected brain regions by a microlysate ribonuclease protection assay. In the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis (DBB(ovlt)), GABAergic neuronal activity was significantly reduced during the afternoon of proestrus compared with the morning of either proestrus or metestrus. In the lateral septal nucleus, GABAergic neuronal activity was significantly increased in the afternoon of proestrus compared with the morning. There were no significant effects of time of day or day of estrous cycle in the medial preoptic nucleus, median eminence, ventromedial nucleus, suprachiasmatic nucleus, medial septal nucleus, hippocampus (CA1 region), or cingulate cortex. In the DBB(ovlt), mRNA levels for both GAD65 and GAD67 were significantly reduced in the afternoon of proestrus compared with the afternoon of metestrus. By contrast, there was no change in GAD65 and GAD67 mRNA levels in the cingulate cortex at any of the times examined. These results demonstrate that GABAergic neuronal activity, and mRNA levels for both GAD65 and GAD67, are reduced in the DBB(ovlt) during the afternoon of proestrus. These results support the hypothesis that decreased GABAergic neuronal activity in this region plays a major permissive role in the generation and maintenance of the estrogen-induced LH surge.
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PMID:GABAergic neuronal activity and mRNA levels for both forms of glutamic acid decarboxylase (GAD65 and GAD67) are reduced in the diagonal band of Broca during the afternoon of proestrus. 889 Dec 47

The principal role of estrogen is its control of the female ovulatory cycle via negative and positive feedback on gonadotropin secretion. However, a detailed, cohesive picture of how the steroid specifically regulates the excitability of hypothalamic neurons involved in the central control of gonadotropin secretion is still emerging. Here, we used an ovariectomized female guinea pig model to test the hypothesis that estrogen acts on GABAergic neurons in the preoptic area (POA) to elicit a biphasic profile of luteinizing hormone (LH) secretion. Intracellular electrophysiological recordings revealed that estradiol benzoate (EB; 25 microgram, s.c.) decreased the hyperpolarizing response of GABAergic neurons to the GABA(B) receptor agonist baclofen 24 hr after treatment. This effect of GABA(B) receptor stimulation in unidentified POA neurons was still depressed 42 hr after EB administration. By the use of a ribonuclease protection assay, however, EB reduced glutamic acid decarboxylase mRNA expression 42 hr but not 24 hr after its administration. Thus, estrogen attenuated the autoinhibition of GABAergic POA neurons during the initial LH suppressive (i.e., negative feedback) phase and subsequently reduced GABAergic function during the LH surge (i.e., positive feedback). These studies demonstrate that the effects of estrogen on hypothalamic GABAergic neurons coincide with the inhibitory and stimulatory actions, respectively, of the steroid on LH secretion. Furthermore, the data provide novel insights into the mechanism by which estrogen regulates hypothalamic GABAergic neurons, which are critical for the biphasic modulation of LH release observed over the course of the female ovulatory cycle.
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PMID:Estrogen biphasically modifies hypothalamic GABAergic function concomitantly with negative and positive control of luteinizing hormone release. 1124 92

Inositolphosphates and phosphatidylinositides are important second messengers. Previously p42(IP4), a protein with high affinity for both Ins(1,3,4,5)P(4) and PtdIns(3,4,5)P(3) has been characterized in our laboratory. In the present study mRNA levels of p42(IP4) were quantified during development (ages: 7, 14, 21 days and adult) by means of ribonuclease protection assay in various rat brain regions (cerebellum, cortex, striatum, thalamus, hypothalamus, olfactory bulb, hippocampus and tectum (superior and inferior colliculus)). A high level of p42(IP4) mRNA was detected in the cortex (ca. 1 pg specific RNA per microg of total RNA) which stayed highly independent of the age of the animals. In hippocampus and in the thalamus, p42(IP4) mRNA levels were comparable to those in the cortex in the first and second week postnatally, but decreased to lower levels in the adult brain. In striatum, the mRNA increased, albeit less intensely than in hippocampus and thalamus, until day 21 postnatally, and then decreased in the adult rat brain. Cerebellar p42(IP4) mRNA showed a slow increase within the first 3 weeks postnatally, and remained rather high in the adult brain. The protein expression of p42(IP4), tested within the same samples by Western blot staining, was consistent with mRNA values. For comparison, glutamic acid decarboxylase (isoforms GAD65/GAD67), an enzyme, for which some regional brain specific distribution is already known, was also examined. The mRNA levels of GAD and its developmental regulation clearly differed from that of p42(IP4). In summary, p42(IP4) expressed in several neuronal cell types, did not seem to be restricted to specific developmental stages, but the high absolute expression levels at all developmental stages indicated that p42(IP4) is a protein fundamental for neuronal functioning.
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PMID:Expression of the brain-specific membrane adapter protein p42IP4/centaurin alpha, a Ins(1,3,4,5)P4/PtdIns(3,4,5)P3 binding protein, in developing rat brain. 1269 46

The present study tested the hypothesis that estradiol reduces tissue infarction after middle cerebral artery occlusion (MCAO) in estradiol-deficient females by augmenting glutamic acid decarboxylase (GAD) expression and thus activity, leading to increases in gamma-amino-butyric acid (GABA) tissue levels. Glutamic acid decarboxylase is the principal enzyme for GABA synthesis and has two isoforms, GAD65 and GAD67, which differ in size and cellular distribution. Rats were ovariectomized 7 to 8 days before receiving no hormone, placebo, or 25 microg estradiol via subcutaneous implant 7 to 10 days before harvesting tissue in either ischemic cohorts after 2 h of MCAO (end-ischemia) or in nonischemic cohorts. Selected cortical and striatal regions were microdissected from harvested brains. GAD65/67 mRNA levels were determined by microlysate ribonuclease protection assay. End-ischemic GABA concentrations were determined by HPLC. Steroid treatment selectively decreased ischemic cortical GAD67 mRNA levels. In most brain regions evaluated, regional GABA concentrations increased with ischemia regardless of treatment. Estradiol blocked MCAO-induced increases in GABA concentration only in dorsomedial cortex. These data suggest that estradiol repletion in ischemic rat brain selectively decreases GAD67 mRNA levels but does not alter steady-state GABA concentrations. It may be that estradiol under ischemic conditions is attenuating GABA metabolism rather than enhancing synthesis or is augmenting other aspects of GABAergic transmission such as GABA transporters and receptors.
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PMID:Estradiol alters only GAD67 mRNA levels in ischemic rat brain with no consequent effects on GABA. 1609 13

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