Universität zu Köln

Alpdogan, Serdar ORCID: 0000-0002-5188-9925, Neumaier, Felix ORCID: 0000-0002-6376-6391, Dibue-Adjei, Maxine, Hescheler, Juergen and Schneider, Toni ORCID: 0000-0003-2816-2696 (2019). Intracerebroventricular administration of histidine reduces kainic acid-induced convulsive seizures in mice. Exp. Brain Res., 237 (10). S. 2481 - 2494. NEW YORK: SPRINGER. ISSN 1432-1106

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Abstract

Kainic acid (KA)-induced seizures and other experimental models of epilepsy have been proven to be instrumental in identifying novel targets that could be responsible for human icto- and epileptogenesis. We have previously shown that the ablation of pharmacoresistant voltage-gated Ca2+ channels with Ca(v)2.3 as central ion-conducting pore (R-type Ca2+ channel) reduces the sensitivity towards KA-induced epilepsy in mice. In vivo, Ca(v)2.3 channels are thought to be under tight allosteric control by endogenous loosely bound trace metal cations (Zn2+ and Cu2+) that suppress channel gating via a highaffinity trace metal-binding site. Metal dyshomeostasis in the brain, which is a common feature of (KA-induced) seizures, could therefore alter the normal function of Ca(v)2.3 channels and may shift hippocampal and neocortical signaling towards hyperexcitation. To investigate the role of loosely bound metal ions for KA-induced hyperexcitation in vivo, we examined the effects of manipulating brain trace metal homeostasis in mice. To this end, we developed a murine system for intracerebroventricular administration of trace metal ions and/or histidine (His), which can bind Zn2+ and Cu2+ and is involved in their transendothelial transport at the blood-brain barrier. Unexpectedly, our preliminary findings indicate that application of His alone but not in the presence of Zn2+ has substantial beneficial effects on the outcome of KA-induced epilepsy in mice. As such, our results emphasize previous findings on the complex, two-sided role of loosely bound metal ions with regard to neuronal excitation and degeneration under pathophysiological conditions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Alpdogan, Serdar UNSPECIFIED orcid.org/0000-0002-5188-9925 UNSPECIFIED Neumaier, Felix UNSPECIFIED orcid.org/0000-0002-6376-6391 UNSPECIFIED Dibue-Adjei, Maxine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Toni UNSPECIFIED orcid.org/0000-0003-2816-2696 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-131662
DOI:	10.1007/s00221-019-05605-z
Journal or Publication Title:	Exp. Brain Res.
Volume:	237
Number:	10
Page Range:	S. 2481 - 2494
Date:	2019
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1106
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Medicine > Physiologie und Pathophysiologie > Institut für Neurophysiologie
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CALCIUM-CHANNELS; BRAIN; ZINC; PERMEABILITY; INHIBITION; MODULATION; CARNOSINE; DRUGS Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13166