The in vivo proconvulsant effects of corticotropin releasing hormone in the developing rat are independent of ionotropic glutamate receptor activation

Brunson, Kristen L.; Schultz, Linda; Baram, Tallie Z.

doi:10.1016/s0165-3806(98)00130-8

Cited by 24 publications

(30 citation statements)

References 45 publications

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“…Second, to determine whether the intense activation of limbic neurons (also induced by CRH) and the resultant induction of signal-transduction cascades (27) were sufficient to alter CRF 1 expression without the requirement for occupancy of this CRH receptor, a similar pattern and degree of limbic neuronal activation were generated by administration of the limbic stimulant, kainic acid (5,11). The compound induced prolonged limbic seizures which were of similar phenotype and duration to those induced by CRH (5,11). In addition, kainic-acid-induced seizures provoked glucocorticoid secretion, resulting in plasma levels similar to those arising from CRH-induced seizures (Fig.…”

Section: Changes In Crf 1 Expression and Binding Require Occupancy Anmentioning

confidence: 85%

“…The convulsant effects of the dose of CRH used here lasted ~3 h (see Ref. 11 for EEG procedures). The specificity of the effects of this dose of CRH was evident from their prevention by preadministration of nonselective antagonists of CRH that block both CRF 1 and CRF 2 receptors.…”

Section: Surgical Procedures and Crh Administrationmentioning

confidence: 99%

“…7) or CRF 1 mRNA expression (Fig. 8): to prevent molecular and electrophysiological measures of neuronal activation, a group of animals were given the short-acting barbiturate, pentobarbital, prior to CRH administration (11,56). As shown in Fig.…”

Section: Changes In Crf 1 Expression and Binding Require Occupancy Anmentioning

confidence: 99%

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Corticotropin-Releasing Hormone (CRH) Downregulates the Function of Its Receptor (CRF1) and Induces CRF1 Expression in Hippocampal and Cortical Regions of the Immature Rat Brain

Brunson

Grigoriadis

Lorang

et al. 2002

Experimental Neurology

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In addition to regulating the neuroendocrine stress response, corticotropin-releasing hormone (CRH) has been implicated in both normal and pathological behavioral and cognitive responses to stress. CRH-expressing cells and their target neurons possessing CRH receptors (CRF 1 and CRF 2 ) are distributed throughout the limbic system, but little is known about the regulation of limbic CRH receptor function and expression, including regulation by the peptide itself. Because CRH is released from limbic neuronal terminals during stress, this regulation might play a crucial role in the mechanisms by which stress contributes to human neuropsychiatric conditions such as depression or posttraumatic stress disorder. Therefore, these studies tested the hypothesis that CRH binding to CRF 1 influenced the levels and mRNA expression of this receptor in stress-associated limbic regions of immature rat. Binding capacities and mRNA levels of both CRF 1 and CRF 2 were determined at several time points after central CRH administration. CRH downregulated CRF 1 binding in frontal cortex significantly by 4 h. This transient reduction (no longer evident at 8 h) was associated with rapid increase of CRF 1 mRNA expression, persisting for >8 h. Enhanced CRF 1 expression-with a different time course-occurred also in hippocampal CA3, but not in CA1 or amygdala, CRF 2 binding and mRNA levels were not altered by CRH administration. To address the mechanisms by which CRH regulated CRF 1 , the specific contributions of ligand-receptor interactions and of the CRH-induced neuronal stimulation were examined. Neuronal excitation without occupation of CRF 1 induced by kainic acid, resulted in no change of CRF 1 binding capacity, and in modest induction of CRF 1 mRNA expression. Furthermore, blocking the neuroexcitant effects of CRH (using pentobarbital) abolished the alterations in CRF 1 binding and expression. These results indicate that CRF 1 regulation involves both occupancy of this receptor by its ligand, as well as "downstream" cellular activation and suggest that stress-induced perturbation of CRH-CRF 1 signaling may contribute to abnormal neuronal communication after some stressful situations.

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Section: Changes In Crf 1 Expression and Binding Require Occupancy Anmentioning

confidence: 85%

Section: Surgical Procedures and Crh Administrationmentioning

confidence: 99%

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Corticotropin-Releasing Hormone (CRH) Downregulates the Function of Its Receptor (CRF1) and Induces CRF1 Expression in Hippocampal and Cortical Regions of the Immature Rat Brain

Brunson

Grigoriadis

Lorang

et al. 2002

Experimental Neurology

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“…To examine further whether endogenous CRF is responsible for modulating ISF A␤ in mice subjected to 3 h of acute restraint stress, 3-month-old Tg2576 mice were pretreated with either vehicle or ␣CRF 9-41 , an antagonist of CRF receptors (17), by reverse microdialysis. ␣CRF 9-41 was continuously infused from 30 min before the onset of 3 h of restraint stress until the end of the experiment.…”

Section: Crf Mediates the Acute Stress-induced Increase In Isf A␤ Levmentioning

confidence: 99%

Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity

Kang¹,

Cirrito²,

Dong³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

206

163

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Aggregation of the amyloid-␤ (A␤) peptide in the extracellular space of the brain is critical in the pathogenesis of Alzheimer's disease. A␤ is produced by neurons and released into the brain interstitial fluid (ISF), a process regulated by synaptic activity. To determine whether behavioral stressors can regulate ISF A␤ levels, we assessed the effects of chronic and acute stress paradigms in amyloid precursor protein transgenic mice. Isolation stress over 3 months increased A␤ levels by 84%. Similarly, acute restraint stress increased A␤ levels over hours. Exogenous corticotropin-releasing factor (CRF) but not corticosterone mimicked the effects of acute restraint stress. Inhibition of endogenous CRF receptors or neuronal activity blocked the effects of acute stress on A␤. Thus, behavioral stressors can rapidly increase ISF A␤ through neuronal activity in a CRF-dependent manner, and the results suggest a mechanism by which behavioral stress may affect Alzheimer's disease pathogenesis.Alzheimer's disease ͉ synaptic activity ͉ environmental stress ͉ microdialysis ͉ transgenic E vidence indicates that the aggregation and accumulation of the amyloid-␤ (A␤) peptide in the brain extracellular space is a key initiating event in the pathogenesis of Alzheimer's disease (AD) (1). A number of studies demonstrate that aggregation of A␤ is concentration-dependent (2). Increasing the amount of A␤ produced by 50% or specifically increasing the more fibrillogenic A␤ 42 either by APP gene dose or mutations in amyloid precursor protein (APP), PS1, or PS2, accelerates the onset of A␤ deposition and AD (3). Conversely, decreasing A␤ by decreasing cleavage of APP or by enhancing clearance of A␤ delays the onset of A␤ deposition (4). Thus, determining factors that regulate the levels of A␤ in the brain extracellular space, where it likely changes conformation and aggregates, may provide insight into AD pathogenesis and treatment.A␤ is produced in the brain primarily by neurons after cleavage of APP by ␤-and ␥-secretase (1). A␤ levels in the extracellular space are then influenced by factors regulating its release from neurons as well as postsecretory events such as transport and clearance. Recent evidence (5, 6) has shown that A␤ release from neurons is regulated by neuronal and specifically synaptic activity over minutes to hours. However, whether behavioral manipulations regulate synaptic activity and interstitial fluid (ISF) A␤ levels has not been addressed.Evidence in both humans and animals suggests that environmental stressors may increase risk for AD or AD pathology. In humans, persons without dementia who are prone to psychological distress are more likely to develop AD (7,8). Also, plasma levels of the stress hormone, cortisol, are correlated with the rate of dementia progression in patients with AD (9). In mouse models of AD, animals subjected to isolation stress over months had decreased learning performance and accelerated A␤ deposition (10). To explore the potential mechanisms and links between behavioral stressors and A...

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“…The role of CRH in mood disorders has been extensively studied (for a review, see Holsboer, 2000) and was not the primary subject of this investigation. However, since CRH, in opposition to NPY, blocks feeding and has proconvulsant effects in rats (Brunson et al, 1998;Krahn et al, 1986), it was of interest to study it in this particular context. Galanin, in similarity to NPY, induces food ingestion in satiated rats and dampens the development of experimental epilepsy (Halford, 2001;Kokaia et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Husum

Kammen

Termeer

et al. 2003

Neuropsychopharmacol

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Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY-and galanin-like immunoreactivities (LI) while NPY-and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.

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The in vivo proconvulsant effects of corticotropin releasing hormone in the developing rat are independent of ionotropic glutamate receptor activation

Cited by 24 publications

References 45 publications

Corticotropin-Releasing Hormone (CRH) Downregulates the Function of Its Receptor (CRF1) and Induces CRF1 Expression in Hippocampal and Cortical Regions of the Immature Rat Brain

Corticotropin-Releasing Hormone (CRH) Downregulates the Function of Its Receptor (CRF1) and Induces CRF1 Expression in Hippocampal and Cortical Regions of the Immature Rat Brain

Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

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