Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cAMP-response element binding protein (CREB) is involved in antidepressant action, but the role of related CRE-binding transcription factors in the behavioral and endocrine responses to antidepressants is unclear. Alternative transcription of the cAMP response element-modulator (CREM) gene yields activator and repressor isoforms, including the strong repressor inducible cAMP early repressor (ICER). ICER is highly expressed in hypothalamic tissues and upregulated after electroconvulsive seizure. Thus, ICER may be a novel mediator of antidepressant action at endocrine and/or behavioral levels. Here we establish that both subchronic and chronic desipramine (DMI) treatments upregulate hypothalamic ICER expression in wild-type mice. Behavioral responses to DMI in the forced swim and tail suspension tests are unchanged in mice lacking ICER. However, the ability of DMI to suppress an acute corticosterone response after swim stress is compromised in ICER-deficient mice, suggesting that increased hypothalamic ICER mRNA after DMI treatment may be required for suppression of corticosterone release. To investigate the mechanism underlying this response, we measured corticotropin releasing factor (CRF), an upstream modulator of corticosterone release. Using real-time quantitative PCR, we establish that hypothalamic CRF expression is significantly reduced after swim exposure in DMI-treated wild-type mice, however DMI is unable to blunt hypothalamic CRF expression in ICER-deficient mice. Furthermore, we demonstrate that ICER is enriched in CRF-expressing neurons in the paraventricular nucleus of the hypothalamus. These data indicate that ICER is required for DMI to reduce stress-induced corticosterone release through regulation of hypothalamic CRF expression, revealing a novel role for ICER in antidepressant regulation of the hypothalamic-pituitary adrenal axis.
 ...
PMID:Inducible cAMP early repressor regulates corticosterone suppression after tricyclic antidepressant treatment. 1498 39

Convulsions are common complications of shigellosis in children. Corticotropin-releasing hormone (CRH), a stress neurohormone, has been implicated in the susceptibility of young children to seizures. We investigated the role of CRH in Shigella-related seizures. Pretreatment with Shigella dysenteriae sonicate enhanced mice response to pentylenetetrazole (PTZ)-induced seizures. Preinjection of antalarmin, a CRH-receptor 1 antagonist, decreased both the mean convulsion score (MCS: 1.6 vs. 1.1, p<0.05) and the percent of mice having seizures (48% vs. 28%, p=0.03). This indicates that CRH plays a role in the increased susceptibility to seizures following exposure to S. dysenteriae.
 ...
PMID:Involvement of the neuropeptide corticotropin-releasing hormone in an animal model of Shigella-related seizures. 1526 61

Neuropeptide Y (NPY) is one of the most abundant and widely distributed neuropeptides in the mammalian central nervous system (CNS). An overview of the distribution of the G-protein coupled NPY receptor family (Y(1), Y(2), Y(4), Y(5) receptors) in the brain is described. The coexistence of NPY with other neurotransmitters and its wide distribution in several brain areas predict the high importance of NPY as a neuromodulator. Thus, the effect of NPY on the release of several neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA), norepinephrine (NE), dopamine, somastotatin (SOM), serotonin (5-HT), nitric oxide (NO), growth hormone (GH) and corticotropin releasing factor (CRF) is reviewed. A neuroprotective role for NPY under physiological conditions and during hyperactivity such as epileptic-seizures has been suggested. We have shown previously that NPY inhibits glutamate release evoked from hippocampal nerve terminals and has a neuroprotective effect in rat organotypic hippocampal cultures exposed to an excitotoxic insult. Moreover, changes in NPY levels have been observed in different pathological conditions such as brain ischemia and neurodegenerative diseases (Huntington's, Alzheimer's and Parkinson's diseases). Taken together, these studies suggest that NPY and NPY receptors may represent pharmacological targets in different pathophysiological conditions in the CNS.
 ...
PMID:The putative neuroprotective role of neuropeptide Y in the central nervous system. 1610 53

Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.
 ...
PMID:Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor. 1702 40

Established treatments for depression are often effective. However, a significant number of patients show limited or no response. With advancements in the explanation of the underlying neurobiology of depression, several novel therapeutic approaches have been developed. Emerging drug targets include novel monoamine oxidase inhibitors, triple monoamine re-uptake inhibitors, omega-3 fatty acids, melatoninergic agonists and receptor antagonists for corticotropin-releasing factor(1), glucocorticoid, substance-P and NMDA. Developments in therapeutic focal brain stimulation include vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation. The role of psychotherapy, both as monotherapy and as adjunctive therapy, is an active avenue of investigation. Although data on these treatments are limited, preliminary results are encouraging. A major goal that remains to be achieved is the identification of predictors of response to the various antidepressant treatments that have diverse mechanisms of action.
 ...
PMID:Emerging treatments for depression. 1710 9

The present studies characterize working memory capabilities in the El mouse model of epilepsy using a species-typical social recognition memory task. As the El mouse exhibits a stress hyper-reactivity phenotype, the impact of hypertonic saline consumption, a memory modulatory treatment, upon social recognition performance was also examined. The hypotheses under test were: (1) that seizure susceptible El mice would perform poorly in the short-term working memory task relative to seizure resistant ddY controls, and (2) that the behavioral and neural responses to stressor exposure would be atypical in El mice. Results revealed a short-term working memory deficit and altered reactivity to social, environmental, and physiological stressors in El mice. In Experiment 1, El mice exhibited poor sociability and decreased olfactory investigation times, both anxiogenic-like traits, compared to ddY controls. In Experiment 2, El mice exhibited poor working memory performance compared to capable performance in ddY controls. Social recognition memory in ddY mice was abolished, however, by salt-loading whereas El mice were unaffected by exposure to this physiological stressor. In Experiment 3, all salt-loaded mice exhibited enhanced brain stress neuropeptide (corticotropin releasing factor-CRF) content, and salt-loaded El mice exhibited a 70% reduction in handling-induced seizures. These findings suggest that El mice exhibit high emotionality as well as atypical reactions to stressor exposure, and that these characteristics impact social working memory performance and seizure susceptibility.
Seizure 2007 Jan
PMID:Short-term social recognition memory deficit and atypical social and physiological stressor reactivity in seizure-susceptible El mice. 1711 13

The effects of centrally administered tripeptide fragment CRF(4-6) of corticotropin-releasing factor on convulsive activity in outbred albino rats were investigated. The peptide CRF(4-6) (icv; 6, 30, 150 nmol/head) causes dose-dependent increase in total EEG power in 1-40 Hz frequency range as a reflection of tripeptide-induced various epileptiform EEG signs such as single peaks and spike trains without external convulsion. Higher doses of CRF(4-6) (icv; 150, 225, 300 nmol per animal) induce tonicoclonic seizures. Switching to convulsive activity occurs at CRF(4-6) dose of 150 nmol per animal: injection of this dose leads only to EEG paroxysmal activity under habitual conditions and induces pathological locomotor activation under stressing conditions. Thus, CRF(4-6) similarly to full-length corticotropin-releasing factor induces epileptiform activity in rats.
 ...
PMID:[Epileptogenic activity of tripeptide corticotropin-releasing factor fragment (CRF(4-6))]. 1728 74

The El mouse strain provides a non-induced model of idiopathic, multifactorial epilepsy in which seizures are elicited in response to stressful environmental stimuli such as tail suspension handling. In the present studies, genetically seizure susceptible El and non-susceptible ddY control mice were exposed to tail suspension, foot-shock and social stressors in order to test the hypothesis that neural and physiological responses to such stimuli would be exaggerated in the El strain. The first experiment assessed neural cell density, stress neuropeptide (corticotropin releasing factor--CRF) levels, and plasma corticosterone activation in El and ddY mice in an unhandled control condition or following exposure to tail suspension or foot-shock stressors. The second experiment assessed brain electroencephalographic activity using telemetrically monitored skull surface electrodes in El and ddY mice exposed to tail suspension or social interaction stressors. Assessment of El mouse brains revealed higher cell counts in amygdala and elevated CRF peptide content in the paraventricular thalamic nucleus relative to ddY controls. El mice exhibited significantly elevated plasma corticosterone levels 60 min following exposure to tail suspension and foot-shock stressors relative to ddY controls. Finally, El mice exhibited significantly elevated brain electroencephalographic (1-4 Hz) activity in response to tail suspension, but not social interaction, relative to ddY controls. These results indicate that potentiated neural, endocrine and physiological activation arises in the El strain following exposure to a known seizure trigger stimulus, involuntary tail suspension handling. The findings support a diathesis-stress hypothesis in which genetically seizure susceptible El mice exhibit a multifaceted hyperreactivity to noxious environmental stimuli.
 ...
PMID:Neural, endocrine and electroencephalographic hyperreactivity to human contact: a diathesis-stress model of seizure susceptibility in El mice. 1732 61

Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are pivotal mediators of the hormonal response to stressors and are found within neurons of the paraventricular nucleus of the hypothalamus (PVN) and several extrahypothalamic sites where expression is activity-dependent. Previous work has shown increased CRH immunoreactivity in extrahypothalamic sites after kainic-acid (KA)-induced seizures in male rats. This study examined the induction of CRH heterogeneous nuclear RNA (hnRNA), AVP hnRNA and c-fos as a measure of gene transcription and cell activation following kainic-acid (KA)-induced seizures. KA or saline was administered to intact male rats, ovariectomized (OVX) females and OVX females treated with 17beta-estradiol (E2). Animals were sacrificed 0, 15, 60 or 120 min following KA treatment. In the PVN, CRH hnRNA levels were increased by KA treatment at 15, 60, and 120 min. AVP hnRNA and c-fos mRNA in the PVN were also significantly elevated above controls at all time points. Elevations in CRH hnRNA were also identified in hippocampus, the lateral bed nucleus of the stria terminalis (BNST) and globus pallidus at 60 and 120 min following KA and in the piriform cortex, and central nucleus of the amygdala at 120 min after KA. CRH hnRNA levels at 120 min in the PVN, amygdala, cingulate cortex, hippocampus (CA1), piriform cortex, and BNST were lower in OVX+E2 females compared to females without E2. To determine if the increases in CRH hnRNA translated to increased CRH peptide, immunocytochemistry was performed. CRH immunoreactivity was increased in the amygdala, BNST, cingulate cortex, PVN and globus pallidus within 3 h after KA treatment and in the piriform cortex and hippocampus by 6 h after KA. These results suggest a time-dependent activation of the CRH system following activation of kainate receptors, which may result in long-term changes in the expression of extrahypothalamic CRH.
 ...
PMID:Corticotropin-releasing hormone heterogeneous nuclear RNA (hnRNA) and immunoreactivity are induced in extrahypothalamic brain sites by kainic-acid-induced seizures and are modulated by estrogen. 1763 70

Alterations in the complexity of social and physical housing environments modulate seizure susceptibility in animal models of epilepsy. The studies described here tested the hypothesis that environmental enrichment would delay seizure onset in the epileptic (El) mouse. Neural activation measured via cFos expression, accumulation of the stress neuropeptide corticotropin-releasing factor (CRF), and behavioral seizure susceptibility were quantified in El mice to better understand the mechanisms of ictogenesis. Enrichment housing of El mice from Postnatal Days 21 to 49 produced a 100% decrease in seizure susceptibility relative to El controls. cFos expression increased in the primary motor cortex, locus ceruleus, and hippocampus of El mice relative to ddY controls, an effect attenuated by enrichment housing. CRF levels were elevated by enrichment in the hippocampus of ddY mice only. This study provides evidence that enrichment housing delays the onset of seizure susceptibility in El mice while altering the neuronal and stress-related responses in seizure-associated regions of the El brain.
 ...
PMID:Seizure susceptibility and locus ceruleus activation are reduced following environmental enrichment in an animal model of epilepsy. 1798 40


<< Previous 1 2 3 4 5 Next >>