Activity-regulated cytoskeleton-associated protein (arc) is an immediate early gene (IEG) whose mRNA is targeted to dendrites of activated synapses. The present study investigated the expression of three IEGs, arc and two transcription factors (NGFI-B and Nurr 1), in regions of the brain of rats that were subjected to a single afterdischarge-inducing electrical stimulation of the left amygdala and in the amygdala-kindled rats that developed consecutive generalized seizures. One hour after a single stimulus was administered to non-kindled rats, mRNA levels of arc and Nurr1 increased significantly in the ipsilateral piriform cortex and medial amygdaloid nucleus. mRNA levels of NGFI-B increased significantly in the left piriform cortex, basolateral amygdaloid nucleus and medial amygdaloid nucleus. In the amygdala-kindled rats, mRNAs of the three IEGs increased significantly in bilateral brain regions including the piriform cortex and dentate gyrus at 0.5-1 h after the last generalized kindled seizure, and returned near to basal levels by 6 h after. Photographic emulsion autoradiograms showed that the arc mRNA signals induced by the last generalized kindled seizures were associated with the cell bodies of the dentate granule cell layer and extended beyond the granule cell layer into the molecular layer, which contains the dendrites of granule cells. These results support that arc serves as an effector IEG whose mRNA is associated with synaptic reorganization in kindling.
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http://dx.doi.org/10.1016/j.brainres.2007.10.102 | DOI Listing |
Neurobiol Stress
November 2024
Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
Prog Neurobiol
July 2022
Department of Pharmacology & Physiology, Georgetown University, Washington DC, USA; Interdisciplinary Program in Neuroscience, Georgetown University, Washington DC, USA; Department of Neuroscience, Georgetown University, Washington DC, USA. Electronic address:
There is a large unmet need for improved treatment for temporal lobe epilepsy (TLE); circuit-specific manipulation that disrupts the initiation and propagation of seizures is promising in this regard. The midline thalamus, including the mediodorsal nucleus (MD) is a critical distributor of seizure activity, but its afferent and efferent pathways that mediate seizure activity are unknown. Here, we used chemogenetics to silence input and output projections of the MD to discrete regions of the frontal cortex in the kindling model of TLE in rats.
View Article and Find Full Text PDFJ Physiol Sci
January 2022
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, 1411713116, Tehran, Iran.
The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT receptors. Cognitive impairment is common among people with epilepsy.
View Article and Find Full Text PDFEpilepsia
December 2021
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.
Objective: An attractive target to interfere with epileptic brain hyperexcitability is the enhancement of γ-aminobutyric acidergic (GABAergic) inhibition by inactivation of the GABA-metabolizing enzyme GABA aminotransferase (GABA-AT). GABA-AT inactivators were designed to control seizures by raising brain GABA levels. OV329, a novel drug candidate for the treatment of epilepsy and addiction, has been shown in vitro to be substantially more potent as a GABA-AT inactivator than vigabatrin, an antiseizure drug approved as an add-on therapy for adult patients with refractory complex partial seizures and monotherapy for pediatric patients with infantile spasms.
View Article and Find Full Text PDFEpilepsia
September 2021
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Objective: Focal impaired awareness seizures (FIASs) are the most common seizure type in adults and are often refractory to medication. Management of FIASs is clinically challenging, and new interventions are needed for better seizure control. The amygdala-kindling model is a preclinical model of FIASs with secondary generalization.
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