共查询到20条相似文献,搜索用时 140 毫秒
1.
Progesterone is a neuroactive hormone with non‐genomic effects on GABA A receptors (GABA AR). Changes in the expression of GABA AR subunits are related to depressive‐like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABA AR α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats ( n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg –1) or vehicle, during two complete female estrous cycles (8–10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive‐like behaviors and GABA AR α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABA AR γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABA A system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABA AR α1 subunit expression in the right prefrontal cortex of female rats. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
2.
Aims Rutin is one of the flavonoids that has many beneficial effects on the health. Previously, we showed that rutin has a protective
effect on trimethyltin (TMT)-induced memory dysfunction in rats. The aim of this study was to investigate the protective effects
of rutin on TMT-induced hippocampal injury and the time course profiles of these effects in rats. Methods Four-week-old male Sprague-Dawley (SD) rats were fed chow with or without rutin (0.75%) during the experimental period and
were administered with a single dose of TMT (8.5 mg/kg b.w., p.o.) or vehicle at 6 weeks of age. The rats were sacrificed
5, 10, or 20 days after the TMT administration and then histological and molecular examinations of the hippocampus were performed.
Results Rutin supplementation suppressed the TMT-induced decrease in the number of hippocampal pyramidal neurons 20 days after TMT
administration. The TMT-induced up-regulation of the mRNA expression levels of reactive microglia marker and pro-inflammatory
cytokines were reversed by rutin supplementation 10 or 20 days after the TMT administration. Conclusions These results suggested that the neuroprotective effect of rutin on TMT-induced spatial memory impairment could be attributable
to its inhibitory effect against microglial activation and its role in synapse formation via neurotrophic factors in the hippocampus. 相似文献
3.
Previous research indicates that the GABA Aergic system is involved in the pathophysiology of the fragile X syndrome, a frequent form of inherited intellectual disability and associated with autism spectrum disorder. However, the molecular mechanism underlying GABA Aergic deficits has remained largely unknown. Here, we demonstrate reduced mRNA expression of GABA A receptor subunits in the cortex and cerebellum of young Fmr1 knockout mice. In addition, we show that the previously reported underexpression of specific subunits of the GABA A receptor can be corrected in YAC transgenic rescue mice, containing the full-length human FMR1 gene in an Fmr1 knockout background. Moreover, we demonstrate that FMRP directly binds several GABA A receptor mRNAs. Finally, positive allosteric modulation of GABA A receptors with the neurosteroid ganaxolone can modulate specific behaviors in Fmr1 knockout mice, emphasizing the therapeutic potential of the receptor. 相似文献
4.
The equilibrium potential for GABA-A receptor mediated currents (E GABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K +/Cl - co-transporter (KCC2) but a relatively high expression of Na +-K +-Cl - cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in E GABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on E GABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus E GABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in E GABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in E GABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in E GABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary. 相似文献
5.
Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine well known for its role in inflammation enhancement. However, a growing body of evidence is emerging on its role in energy metabolism in insulin sensitive tissues such as hippocampus, a brain region implicated in cognition, learning and memory. We hypothesized that genetic deletion of MIF may result in the specific behavioral changes, which may be linked tо impairments in brain or systemic insulin sensitivity by possible changes of the hippocampal synaptic plasticity. To assess memory, exploratory behavior and anxiety, three behavioral tests were applied on Mif gene-deficient (MIF −/−) and “wild type” C57BL/6J mice (WT). The parameters of systemic and hippocampal insulin sensitivity were also determined. The impact of MIF deficiency on hippocampal plasticity was evaluated by analyzing the level of synaptosomal polysialylated-neural cell adhesion molecule (PSA-NCAM) plasticity marker and mRNA levels of different neurotrophic factors.The results showed that MIF −/− mice exhibit emphasized anxiety-like behaviors, as well as impaired recognition memory, which may be hippocampus-dependent. This behavioral phenotype was associated with impaired systemic insulin sensitivity and attenuated hippocampal insulin sensitivity, characterized by increased inhibitory Ser 307 phosphorylation of insulin receptor substrate 1 (IRS1). Finally, MIF −/− mice displayed a decreased hippocampal PSA-NCAM level and unchanged Bdnf, NT- 3, NT- 4 and Igf- 1 mRNA levels.The results suggest that the lack of MIF leads to disturbances of systemic and hippocampal insulin sensitivity, which are possibly responsible for memory deficits and anxiety, most likely through decreased PSA-NCAM-mediated neuroplasticity rather than through neurotrophic factors. 相似文献
6.
Abstract: The GABA A receptor is a heterooligomeric protein complex composed of multiple receptor subunits. Developmental changes in the pattern of expression of 11 GABA A receptor subunits in individual rat embryonic hippocampal neurons on days 1–21 in culture and acutely dissociated hippocampal neurons from postnatal day (PND) 5 rat pups were investigated using the technique of single-cell mRNA amplification. We demonstrate that multiple GABA A receptor subunits are expressed within individual hippocampal neurons, with most cells simultaneously expressing α1, α2, α5, β1, and γ2 mRNAs. Further, relative expression of several GABA A receptor subunit mRNAs changes significantly in embryonic hippocampal neurons during in vitro development, with the relative abundance (compared with β-actin) of α1, α5, and γ2 mRNAs increasing 2.3-, 2.7-, and 3.8-fold, respectively, from days 1 to 14, and β1 increasing 5-fold from days 1 to 21. In situ hybridization with antisense digoxigenin-labeled α1, β1, and γ2 RNA probes demonstrates a similar increase in expression of subunit mRNAs as embryonic hippocampal neurons mature in vitro. Relative abundances of α1, β1, and γ2 subunit mRNAs in acutely dissociated PND 5 hippocampal neurons are also significantly greater than in embryonic day 17 neurons on day 1 in vitro and exceed the peak values seen in cultured neurons on days 14–21, suggesting that GABA A receptor subunit mRNA expression within individual hippocampal neurons follows a similar, if somewhat delayed, developmental pattern in vitro compared with in vivo. These findings suggest that embryonic hippocampal neuronal culture provides a useful model in which to study the developmental regulation of GABA A receptor expression and that developmental changes in GABA A receptor subunit expression may underlie some of the differences in functional properties of GABA A receptors in neonatal and mature hippocampal neurons. 相似文献
7.
The neurosteroid allopregnanolone is a potent positive allosteric modulator of GABA action at GABA A receptors. Allopregnanolone is synthesized in the brain from progesterone by the sequential action of 5α-reductase type I
(5α-RI) and 3α-hydroxysteroid dehydrogenase (3α-HSD). 5α-RI and 3α-HSD are co-expressed in cortical, hippocampal, and olfactory
bulb glutamatergic neurons and in output neurons of the amygdala, thalamus, cerebellum, and striatum. Neither 5α-RI nor 3α-HSD
mRNAs is expressed in glial cells or in cortical or hippocampal GABAergic interneurons. It is likely that allopregnanolone
synthesized in principal output neurons locally modulates GABA A receptor function by reaching GABA A receptor intracellular sites through lateral membrane diffusion.
This review will focus on the behavioral effects of allopregnanolone on mouse models that are related to a sexually dimorphic
regulation of brain allopregnanolone biosynthesis. Animal models of psychiatric disorders, including socially isolated male
mice or mice that receive a long-term treatment with anabolic androgenic steroids (AAS), show abnormal behaviors such as altered
fear responses and aggression. In these animal models, the cortico-limbic mRNA expression of 5α-RI is regulated in a sexually
dimorphic manner. Hence, in selected glutamatergic pyramidal neurons of the cortex, CA3, and basolateral amygdala and in granular
cells of the dentate gyrus, mRNA expression of 5α-RI is decreased, which results in a downregulation of allopregnanolone content.
In contrast, 5α-RI mRNA expression fails to change in the striatum medium spiny neurons and in the reticular thalamic nucleus
neurons, which are GABAergic.
By manipulating allopregnanolone levels in glutamatergic cortico-limbic neurons in opposite directions to improve [using the
potent selective brain steroidogenic stimulant (SBSS) S-norfluoxetine] or induce (using the potent 5α-RI inhibitor SKF 105,111)
behavioral deficits, respectively, we have established the fundamental role of cortico-limbic allopregnanolone levels in the
sexually dimorphic regulation of aggression and fear. By selectively targeting allopregnanolone downregulation in glutamatergic
cortico-limbic neurons, i.e., by improving the response of GABA A receptors to GABA, new therapeutics would offer appropriate and safe management of psychiatric conditions, including impulsive
aggression, irritability, irrational fear, anxiety, posttraumatic stress disorders, and depression.
Special issue article in honor of Dr. Ji-Sheng Han. 相似文献
8.
The proliferation and differentiation of neural progenitor (NP) cells can be regulated by neurotransmitters including GABA and dopamine. The present study aimed to examine how these two neurotransmitter systems interact to affect post‐natal hippocampal NP cell proliferation in vitro. Mouse hippocampal NP cells express functional GABA A receptors, which upon activation led to an increase in intracellular calcium levels via the opening of L‐type calcium channels. Activation of these GABA A receptors also caused a significant decrease in proliferation; an effect that required the entry of calcium through L‐type calcium channels. Furthermore, while activation of D 1‐like dopamine receptors had no effect on proliferation, it abrogated the suppressive effects of GABA A receptor activation on proliferation. The effects of D 1‐like dopamine receptors are associated with a decrease in the ability of GABA A receptors to increase intracellular calcium levels, and a reduction in the surface expression of GABA A receptors. In this way, D 1‐like dopamine receptor activation can increase the proliferation of NP cells by preventing GABA A receptor‐mediated inhibition of proliferation. These results suggest that, in conditions where NP cell proliferation is under the tonic suppression of GABA, agonists which act through D 1‐like dopamine receptors may increase the proliferation of neural progenitors. 相似文献
10.
Anatomical evidence indicates that γ-aminobutyric acid (GABA)-ergic and opioidergic systems are closely linked and act on
the same neurons. However, the regulatory mechanisms between GABAergic and opioidergic system have not been well characterized.
In the present study, we investigated whether there are changes in GABA A receptors in mice lacking μ-opioid receptor gene. The GABA A receptor binding was carried out by autoradiography using [ 3H]-muscimol (GABA A), [ 3H]-flunitrazepam (FNZ, native type 1 benzodiazepine) and [ 35S]- t-butylbicyclophosphorothionate (TBPS, binding to GABA A-gated chloride channels) in brain slices of wild type and μ-opioid receptor knockout mice. The binding of [ 3H]-FNZ in μ-opioid receptor knockout mice was significantly higher than that of the wild type controls in most of the cortex
and hippocampal CA1 and CA2 formations. μ-Opioid receptor knockout mice show significantly lower binding of [ 35S]-TBPS than that of the wild type mice in few of the cortical areas including ectorhinal cortex layers I, III, and V, but
not in the hippocampus. There was no significant difference in binding of [ 3H]-muscimol between μ-opioid receptor knockout and wild type mice in the cortex and hippocampus. These data indicate that
there are specific regional changes in GABA A receptor binding sites in μ-opioid receptor knockout mice. These data also suggest that there are compensatory up-regulation
of benzodiazepine binding site of GABA A receptors in the cortex and hippocampus and down-regulation of GABA-gated chloride channel binding site of GABA A receptors in the cortex of the μ-opioid receptor knockout mice. 相似文献
11.
Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue sydrome (CFS) and neuron
apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis.
We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral
weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and
CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in
the CFS model and TJ-41 treated mice, while no significant difference was found between them. We improved a murine model to
investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated
with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running
activity of the model, which was independent of brain recovery. 相似文献
12.
Astrocytes are the major glial cells in brain tissue and are involved, among many functions, ionic and metabolic homeostasis maintenance of synapses. These cells express receptors and transporters for neurotransmitters, including GABA. GABA signaling is reportedly able to affect astroglial response to injury, as evaluated by specific astrocyte markers such as glial fibrillary acid protein and the calcium-binding protein, S100B. Herein, we investigated the modulatory effects of the GABAA receptor on astrocyte S100B secretion in acute hippocampal slices and astrocyte cultures, using the agonist, muscimol, and the antagonists pentylenetetrazol (PTZ) and bicuculline. These effects were analyzed in the presence of tetrodotoxin (TTX), fluorocitrate (FLC), cobalt and barium. PTZ positively modify S100B secretion in hippocampal slices and astrocyte cultures; in contrast, bicuculline inhibited S100B secretion only in hippocampal slices. Muscimol, per se, did not change S100B secretion, but prevented the effects of PTZ and bicuculline. Moreover, PTZ-induced S100B secretion was prevented by TTX, FLC, cobalt and barium indicating a complex GABAA communication between astrocytes and neurons. The effects of two putative agonists of GABAA, β-hydroxybutyrate and methylglyoxal, on S100B secretion were also evaluated. In view of the neurotrophic role of extracellular S100B under conditions of injury, our data reinforce the idea that GABAA receptors act directly on astrocytes, and indirectly on neurons, to modulate astroglial response. 相似文献
13.
Abstract: We have shown that the vertebrate neuropeptide N-acetylaspartylglutamate (NAAG) meets the criteria for a neurotransmitter, including function as a selective metabotropic glutamate receptor (mGluR) 3 agonist. Short-term treatment of cerebellar granule cells with NAAG (30 µ M) results in the transient increase in content of GABA Aα6 subunit mRNA. Using quantitative PCR, this increase was determined to be up to 170% of control values. Similar effects are seen following treatment with trans-1-aminocyclopentane-1,3-dicarboxylate and glutamate and are blocked by the mGluR antagonists (2 S,3 S,4 S)-2-methyl-2-(carboxycyclopropyl)glycine and (2 S)-α-ethylglutamic acid. The effect is pertussis toxin-sensitive. The increase in α6 subunit mRNA level can be simulated by activation of other receptors negatively linked to adenylate cyclase activity, such as adenosine A1, α2-adrenergic, muscarinic, and GABA B receptors. Forskolin stimulation of cyclic AMP (cAMP) levels abolished the effect of NAAG. The change in α6 levels induced by 30 µ M NAAG can be inhibited in a dose-dependent manner by simultaneous application of increasing doses of the β-adrenergic receptor agonist isoproterenol. The increase in α6 mRNA content is followed by a fourfold increase in α6 protein level 6 h posttreatment. Under voltage-clamped conditions, NAAG-treated granule cells demonstrate an increase in the furosemide-induced inhibition of GABA-gated currents in a concentration-dependent manner, indicating an increase in functional α6-containing GABA A receptors. These data support the hypothesis that NAAG, acting through mGluR3, regulates expression of the GABA Aα6 subunit via a cAMP-mediated pathway and that cAMP-coupled receptors for other neurotransmitters may similarly influence GABA A receptor subunit composition. 相似文献
14.
Recent studies have suggested that the GABA A, receptor complex, the site of action of the inhibitory neurotransmitter gamma amino-butyric acid (GABA A) and the anxiolytic benzodiazepines, is heterogeneous. Moreover, its composition may change during development. To better understand the molecular basis of receptor heterogeneity, the levels and distribution of the mRNA encoding the α1 receptor subunit were examined in the developing and adult rat brain with quantitative in situ hybridization histochemistry. Our studies demonstrate that α1 subunit mRNA expression changes during ontogeny. At late embryonic stages and in the first postnatal week, low levels of the mRNA were detected in the cortex, inferior colliculus, and hippocampus. The mRNA levels in these regions increased during the second and third postnatal weeks. Furthermore, a dramatic change in the distribution of the α1 subunit mRNA was seen in the second postnatal week when the message first became detectable in the cerebellar cortex. During subsequent development and in the mature brain, the α1 subunit mRNA was most abundant in the cerebellum, olfactory bulb, and inferior colliculus, although the absolute levels of mRNA varied by as much as sixfold in selected brain regions. The mature distribution of α1 subunit mRNA, along with its temporal appearance in the cerebellum, suggests that this subunit is a constituent of the Type 1 benzodiazepine site of the GABA A receptor complex. Furthermore, the onset of α1 subunit mRNA expression in the cerebellar cortex coincides with a period of extensive synapse formation, raising the possibility that synaptic interactions modulate the appearance of this GABA A receptor subunit in the cerebellum. 相似文献
15.
GABA B receptors function as heterodimeric G-protein-coupled receptors for the neurotransmitter γ-aminobutyric acid (GABA). Receptor subtypes, based on isoforms of the ligand-binding subunit GABA B1, are thought to involve a differential set of associated proteins. Here, we describe two mouse lines that allow a straightforward biochemical isolation of GABA B receptors. The transgenic mice express GABA B1 isoforms that contain sequences for a two-step affinity purification, in addition to their endogenous subunit repertoire. Comparative analyses of purified samples from the transgenic mice and wild-type control animals revealed two novel components of the GABA B1 complex. One of the identified proteins, potassium channel tetramerization domain-containing protein 12, associates with heterodimeric GABA B receptors via the GABA B2 subunit. In transfected hippocampal neurons, potassium channel tetramerization domain-containing protein 12 augmented axonal surface targeting of GABA B2. The mice equipped with tags on GABA B1 facilitate validation and identification of native binding partners of GABA B receptors, providing insight into the molecular mechanisms of synaptic modulation. 相似文献
16.
The responses of inhibitory neurons/synapses to motoneuron injury in the cranial nervous system remain to be elucidated. In this study, we analyzed GABA A receptor (GABA AR) and GABAergic neurons at the protein level in the transected rat facial nucleus. Immunoblotting revealed that the GABA ARα1 protein levels in the axotomized facial nucleus decreased significantly 5–14 days post-insult, and these levels remained low for 5 weeks. Immunohistochemical analysis indicated that the GABA ARα1-expressing cells were motoneurons. We next examined the specific components of GABAergic neurons, including glutamate decarboxylase (GAD), vesicular GABA transporter (VGAT) and GABA transporter-1 (GAT-1). Immunoblotting indicated that the protein levels of GAD, VGAT and GAT-1 decreased transiently in the transected facial nucleus from 5 to 14 days post-insult, but returned to the control levels at 5 weeks post-insult. Although GABA ARα1 protein levels in the transected nucleus did not return to their control levels for 5 weeks post-insult, the administration of glial cell line—derived neurotrophic factor at the cut site significantly ameliorated the reductions. Through these findings, we verified that the injured facial motoneurons suppressed the levels of GABA ARα1 protein over the 5 weeks post-insult, presumably due to the deprivation of neurotrophic factor. On the other hand, the levels of the GAD, VGAT and GAT-1 proteins in GABAergic neurons were transiently reduced in the axotomized facial nucleus at 5–14 days post-insult, but recovered at 4–5 weeks post-insult. 相似文献
17.
GABA B receptors are the G‐protein‐coupled receptors for the neurotransmitter γ‐aminobutyric acid (GABA). Receptor subtypes are based on the subunit isoforms GABA B1a and GABA B1b, which combine with GABA B2 subunits to form heteromeric receptors. Here, we used a modified bacterial artificial chromosome (BAC) containing the GABAB1 gene to generate transgenic mice expressing GABA B1a and GABA B1b subunits fused to the enhanced green fluorescence protein (eGFP). We demonstrate that the GABA B1‐eGFP fusion proteins reproduce the cellular expression patterns of endogenous GABA B1 proteins in the brain and in peripheral tissue. Crossing the GABAB1‐eGFP BAC transgene into the GABAB1?/? background restores pre and postsynaptic GABA B functions, showing that the GABA B1‐eGFP fusion proteins substitute for the lack of endogenous GABA B1 proteins. Finally, we demonstrate that the GABA B1‐eGFP fusion proteins replicate the temporal expression patterns of native GABA B receptors in cultured neurons. These transgenic mice therefore provide a validated tool for direct visualization of native GABA B receptors. genesis 47:595–602, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
18.
BackgroundTaurine is one of the most abundant free amino acids especially in excitable tissues, with wide physiological actions. Chronic supplementation of taurine in drinking water to mice increases brain excitability mainly through alterations in the inhibitory GABAergic system. These changes include elevated expression level of glutamic acid decarboxylase (GAD) and increased levels of GABA. Additionally we reported that GABAA receptors were down regulated with chronic administration of taurine. Here, we investigated pharmacologically the functional significance of decreased / or change in subunit composition of the GABAA receptors by determining the threshold for picrotoxin-induced seizures. Picrotoxin, an antagonist of GABAA receptors that blocks the channels while in the open state, binds within the pore of the channel between the β2 and β3 subunits. These are the same subunits to which GABA and presumably taurine binds.MethodsTwo-month-old male FVB/NJ mice were subcutaneously injected with picrotoxin (5 mg kg-1) and observed for a) latency until seizures began, b) duration of seizures, and c) frequency of seizures. For taurine treatment, mice were either fed taurine in drinking water (0.05%) or injected (43 mg/kg) 15 min prior to picrotoxin injection.ResultsWe found that taurine-fed mice are resistant to picrotoxin-induced seizures when compared to age-matched controls, as measured by increased latency to seizure, decreased occurrence of seizures and reduced mortality rate. In the picrotoxin-treated animals, latency and duration were significantly shorter than in taurine-treated animas. Injection of taurine 15 min before picrotoxin significantly delayed seizure onset, as did chronic administration of taurine in the diet. Further, taurine treatment significantly increased survival rates compared to the picrotoxin-treated mice.ConclusionsWe suggest that the elevated threshold for picrotoxin-induced seizures in taurine-fed mice is due to the reduced binding sites available for picrotoxin binding due to the reduced expression of the beta subunits of the GABAA receptor. The delayed effects of picrotoxin after acute taurine injection may indicate that the two molecules are competing for the same binding site on the GABAA receptor. Thus, taurine-fed mice have a functional alteration in the GABAergic system. These include: increased GAD expression, increased GABA levels, and changes in subunit composition of the GABAA receptors. Such a finding is relevant in conditions where agonists of GABAA receptors, such as anesthetics, are administered. 相似文献
19.
ABSTRACTThis study aims to study the effects of adenosine A 2A receptor (A 2AR) on hippocampal cell apoptosis and the putative mechanisms in a mouse model of chronic hypoxic-hypercapnia. Wild-type (WT) or A 2AR knockout (A 2AR KO) mice were randomly divided into normal control (NC) groups and chronic hypoxic-hypercapnia (4HH) groups. Compared with their corresponding NC groups (WT-NC and KO-NC), the apoptosis index (AI), caspase-3 activity, Bax mRNA and P-p38 protein expression in the hippocampus of 4HH groups (WT-4HH and KO-4HH) were significantly increased, while Bcl2 mRNA expression was significantly decreased (P < 0.05). Moreover, A 2AR deficiency significantly rescued the effect of chronic hypoxic-hypercapnia on apoptosis when compared with the WT-4HH group (P < 0.05). A 2AR deficiency inhibits hippocampal cell apoptosis in mice exposed to chronic hypoxic-hypercapnia, which might be associated with dampened p38 MAPK activation and Bax mRNA expression, and augmented Bcl-2 mRNA expression. 相似文献
|