Opposing reduced VPAC <subscript>1</subscript> and enhanced VPAC <subscript>2</subscript> VIP receptors in the hippocampus of the Li <superscript>2+</superscript> -pilocarpine rat model of temporal lobe epilepsy.

Serpa, A ; Bento, M ; et al.

In: Neurochemistry international, Jg. 158 (2022-09-01), S. 105383

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VIP binding sites are upregulated in mesial temporal lobe epilepsy (MTLE) patients, also suffering from severe cognitive deficits. Although altered VIP and VIP receptor levels were described in rodent models of epilepsy, the VIP receptor subtype(s) were never identified. We now investigated how VPAC 1 and VPAC 2 receptor levels change in the Li 2+ -pilocarpine rat model of MTLE. Cognitive decline and altered synaptic plasticity as estimated from phosphorylation of AMPA GluA1 subunit on Ser831 and Ser845 and AMPA GluA1/GluA2 ratio was also probed. Animals showing spontaneous recurrent seizures (SRSs) for at least 4 weeks showed impaired learning in the radial arm maze (RAM) and presented decreased VPAC 1 and increased VPAC 2 receptor levels. In addition, SRSs rats showed increased AMPA GluA1 phosphorylation in Ser831 and Ser845, marked decrease in GluA1 levels and a milder decrease in GluA2 levels. Consequently, the GluA1/GluA2 ratio was also decreased in SRSs rats. Altered VIP receptor levels may differentially prevent or contribute to MTLE pathology, since VPAC 1 receptors promote the endogenous control of LTP, mediate endogenous VIP neuroprotection against altered synaptic plasticity following epileptiform activity, and mediate anti-inflammatory actions in microglia, while VPAC 2 receptors mediate VIP endogenous neuroprotection against neonatal excitotoxicity and prevent reactive astrogliosis. This discovery imposes a different mindset for considering VIP receptors as therapeutic targets in MTLE, allowing a differential targeting of the cellular events contributing to epileptogenesis.

Titel:	Opposing reduced VPAC <subscript>1</subscript> and enhanced VPAC <subscript>2</subscript> VIP receptors in the hippocampus of the Li <superscript>2+</superscript> -pilocarpine rat model of temporal lobe epilepsy.
Autor/in / Beteiligte Person:	Serpa, A ; Bento, M ; Caulino-Rocha, A ; Pawlak, S ; Cunha-Reis, D
Link:	Zum Volltext
Zeitschrift:	Neurochemistry international, Jg. 158 (2022-09-01), S. 105383
Veröffentlichung:	Oxford [Elmsford, N. Y.] Pergamon Press., 2022
Medientyp:	academicJournal
ISSN:	1872-9754 (electronic)
DOI:	10.1016/j.neuint.2022.105383
Schlagwort:	Animals Hippocampus metabolism Pilocarpine toxicity Rats Seizures metabolism alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Epilepsy, Temporal Lobe chemically induced Epilepsy, Temporal Lobe metabolism Receptors, Vasoactive Intestinal Peptide metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Neurochem Int] 2022 Sep; Vol. 158, pp. 105383. <i>Date of Electronic Publication: </i>2022 Jul 03. MeSH Terms: Epilepsy, Temporal Lobe* / chemically induced ; Epilepsy, Temporal Lobe* / metabolism ; Receptors, Vasoactive Intestinal Peptide* / metabolism ; Animals ; Hippocampus / metabolism ; Pilocarpine / toxicity ; Rats ; Seizures / metabolism ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Contributed Indexing: Keywords: Epilepsy; Hippocampus; Learning and memory; VIP; VPAC(1) receptors; VPAC(2) receptors Substance Nomenclature: 0 (Receptors, Vasoactive Intestinal Peptide) ; 01MI4Q9DI3 (Pilocarpine) ; 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) Entry Date(s): Date Created: 20220705 Date Completed: 20220718 Latest Revision: 20220719 Update Code: 20231215

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