Involvement of cAMP- and Ca2+/calmodulin-dependent neuronal protein phosphorylation in mechanisms underlying genetic predisposition to audiogenic seizures in rats

Yechikhov, Sergey; Morenkov, E. D.; Chulanova, Tatyana; Godukhin, O. V.; Shchipakina, T. G.

doi:10.1016/s0920-1211(01)00255-8

Cited by 33 publications

(20 citation statements)

References 33 publications

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“…Our data (not presented) concerning modulation of AS and postictal catalepsy by haloperidol injections, as well as data from the literature, e.g., [37], confirm such complicated interactions even during development [38]. In KM rats, the striatum DA system was shown to be different from that in rats of nonaudiogenic prone groups.…”

Section: Postictal "Audiogenic" Catalepsysupporting

confidence: 78%

“…The activity of PKA was higher both in the neocortex and in the hippocampus in audiogenic sensitive rats. Daily repeated audiogenic seizures induced a decrease of Ca(2 + )-independent CAMKII activity in the hippocampus and an increase in the neocortical PKA activity in nonseizure-prone animals in comparison to audiogenic rats [37]. In these studies, special attention was paid to the hippocampal physiological and/or morphological traits in KM rats [66].…”

Section: Neurochemical Investigations Of Audiogenic Seizure Pronenessmentioning

confidence: 99%

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The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years

Полетаева

Сурина

Kostina

et al. 2017

Epilepsy & Behavior

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Section: Postictal "Audiogenic" Catalepsysupporting

confidence: 78%

Section: Neurochemical Investigations Of Audiogenic Seizure Pronenessmentioning

confidence: 99%

The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years

Полетаева

Сурина

Kostina

et al. 2017

Epilepsy & Behavior

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“…Because CRF 2 receptors are coupled to AC/cAMP/PKA pathway and there is strong evidence demonstrating that cAMP and PKA signals exert a tonic control of epilepsy [53], [54], [55], [56], [57], [58], we tested the roles of this pathway in CRF-mediated facilitation of epileptiform activity. Slices were pretreated with the selective AC inhibitor MDL 12330A (50 µM) for ∼20 min and the same concentration of MDL 12330A was included in the PTX-containing extracellular solution and applied in the bath before and during the application of CRF.…”

Section: Resultsmentioning

confidence: 99%

Corticotropin-Releasing Factor Facilitates Epileptiform Activity in the Entorhinal Cortex: Roles of CRF2 Receptors and PKA Pathway

2014

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Whereas corticotropin-releasing factor (CRF) has been considered as the most potent epileptogenic neuropeptide in the brain, its action site and underlying mechanisms in epilepsy have not been determined. Here, we found that the entorhinal cortex (EC) expresses high level of CRF and CRF2 receptors without expression of CRF1 receptors. Bath application of CRF concentration-dependently increased the frequency of picrotoxin (PTX)-induced epileptiform activity recorded from layer III of the EC in entorhinal slices although CRF alone did not elicit epileptiform activity. CRF facilitated the induction of epileptiform activity in the presence of subthreshold concentration of PTX which normally would not elicit epileptiform activity. Bath application of the inhibitor for CRF-binding proteins, CRF6-33, also increased the frequency of PTX-induced epileptiform activity suggesting that endogenously released CRF is involved in epileptogenesis. CRF-induced facilitation of epileptiform activity was mediated via CRF2 receptors because pharmacological antagonism and knockout of CRF2 receptors blocked the facilitatory effects of CRF on epileptiform activity. Application of the adenylyl cyclase (AC) inhibitors blocked CRF-induced facilitation of epileptiform activity and elevation of intracellular cyclic AMP (cAMP) level by application of the AC activators or phosphodiesterase inhibitor increased the frequency of PTX-induced epileptiform activity, demonstrating that CRF-induced increases in epileptiform activity are mediated by an increase in intracellular cAMP. However, application of selective protein kinase A (PKA) inhibitors reduced, not completely blocked CRF-induced enhancement of epileptiform activity suggesting that PKA is only partially required. Our results provide a novel cellular and molecular mechanism whereby CRF modulates epilepsy.

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“…It was proposed that increased excitability in neurons underlying epileptic seizures would be maintained by abnormalities in protein phosphorylation systems (15,16). Regulation of NMDA and AMPA (17,18) receptors by cAMP-dependent protein kinase (PKA) is essentialforsynaptictransmission.Ca 2+ influxthrough NMDA receptors is closely related with protein kinase activity.…”

Section: Introductionmentioning

confidence: 99%

Role of cAMP-Dependent Protein Kinase on Acute Picrotoxin-Induced Seizures

2005

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cAMP-dependent protein kinase (PKA) is a major modulator of synaptic transmission likely to be involved in molecular and cellular events leading to epileptogenesis, but little is known about how it affects the onset of acute epileptic seizures. In this study, we determined PKA enzymatic activity in the rat hippocampus during picrotoxin-induced seizures, using H-9 dihydrochloride, a PKA inhibitor, to investigate the in vivo effects of this enzyme on seizures induced by picrotoxin microdialysis in the rat hippocampus. No significant modifications were found in PKA activity during seizures as compared to control rats, but H-9 dihydrochloride microperfusion (100 microM) prevented picrotoxin seizures in 50% of the animals and significantly reduced the mean number of seizures and mean seizure duration. These results suggest that acute picrotoxin-induced seizures occur without an increase in hippocampal PKA activity, but reduced PKA-mediated phosphorylation protects against picrotoxin seizures, probably by increasing the inhibitory potential of GABA(A) receptors. The possibility of other targets for H-9 dihydrochloride, such as PKC, PKG or CAMKII, however, cannot be ruled out.

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Involvement of cAMP- and Ca2+/calmodulin-dependent neuronal protein phosphorylation in mechanisms underlying genetic predisposition to audiogenic seizures in rats

Cited by 33 publications

References 33 publications

The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years

The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years

Corticotropin-Releasing Factor Facilitates Epileptiform Activity in the Entorhinal Cortex: Roles of CRF2 Receptors and PKA Pathway

Role of cAMP-Dependent Protein Kinase on Acute Picrotoxin-Induced Seizures

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