Document type
Journal articles
Document subtype
Full paper
Title
Opposing reduced VPAC1 and enhanced VPAC2 VIP receptors in the hippocampus of the Li2+-pilocarpine rat model of temporal lobe epilepsy
Participants in the publication
André Serpa (Author)
BioISI - Biosystems & Integrative Sciences Institute
Marta Bento (Author)
BioISI - Biosystems & Integrative Sciences Institute
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
Dep. Química e Bioquímica
BioISI
Ana Caulino-Rocha (Author)
Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Portugal.
Seweryn Pawlak (Author)
BioISI - Biosystems & Integrative Sciences Institute
BioISI
Diana Cunha-Reis (Author)
Dep. Química e Bioquímica
BioISI
Summary
VIP binding sites are upregulated in mesial temporal lobe epilepsy (MTLE) patients, also suffering from severe\\ncognitive deficits. Although altered VIP and VIP receptor levels were described in rodent models of epilepsy, the\\nVIP receptor subtype(s) were never identified. We now investigated how VPAC1 and VPAC2 receptor levels\\nchange in the Li2+-pilocarpine rat model of MTLE. Cognitive decline and altered synaptic plasticity as estimated\\nfrom phosphorylation of AMPA GluA1 subunit on Ser831 and Ser845 and AMPA GluA1/GluA2 ratio was also\\nprobed. Animals showing spontaneous recurrent seizures (SRSs) for at least 4 weeks showed impaired learning in\\nthe radial arm maze (RAM) and presented decreased VPAC1 and increased VPAC2 receptor levels. In addition,\\nSRSs rats showed increased AMPA GluA1 phosphorylation in Ser831 and Ser845, marked decrease in GluA1\\nlevels and a milder decrease in GluA2 levels. Consequently, the GluA1/GluA2 ratio was also decreased in SRSs\\nrats.\\nAltered VIP receptor levels may differentially prevent or contribute to MTLE pathology, since VPAC1 receptors\\npromote the endogenous control of LTP, mediate endogenous VIP neuroprotection against altered synaptic\\nplasticity following epileptiform activity, and mediate anti-inflammatory actions in microglia, while VPAC2\\nreceptors mediate VIP endogenous neuroprotection against neonatal excitotoxicity and prevent reactive astro-\\ngliosis. This discovery imposes a different mindset for considering VIP receptors as therapeutic targets in MTLE,\\nallowing a differential targeting of the cellular events contributing to epileptogenesis.
Date of Submisson/Request
2022-05-20
Date of Acceptance
2022-06-27
Date of Publication
2022-09
Institution
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
Where published
Neurochemistry International
Publication Identifiers
ISSN - 0197-0186
Publisher
Elsevier BV
Document Identifiers
DOI -
https://doi.org/10.1016/j.neuint.2022.105383
URL -
http://dx.doi.org/10.1016/j.neuint.2022.105383
Rankings
Web Of Science Q2 (2020) - 3.921 - BIOCHEMISTRY & MOLECULAR BIOLOGY - SCIE
Web Of Science Q2 (2020) - 3.921 - NEUROSCIENCES - SCIE
SCIMAGO Q2 (2020) - 1.241 - Cellular and Molecular Neuroscience
SCOPUS Q2 (2020) - 6.5 - Cellular and Molecular Neuroscience
Web Of Science Q2 (2021) - 4.29 - Neuroscience
Keywords
VIP
epilepsy
hippocampus
VPAC1 receptor
VPAC2 receptor