Anxiety-like features and spatial memory problems as a consequence of hippocampal SV2A expression

TY - JOUR

T1 - Anxiety-like features and spatial memory problems as a consequence of hippocampal SV2A expression

AU - Serrano, Maria Elisa

AU - Bartholomé, Odile

AU - Van den Ackerveken, Priscilla

AU - Ferrara, André

AU - Rogister, Bernard

AU - Plenevaux, Alain

AU - Tirelli, Ezio

PY - 2019

Y1 - 2019

N2 - The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose presence is reduced both in animal models and in patients with chronic epilepsy. Besides its implication in the epileptic process, the behavioural consequences of the changes in its expression remain unclear. The purpose of our research is to better understand the possible role(s) of this protein through the phenotype of cKO (Grik4 Cre+/-, SV2A lox/lox) mice, male and female, which present a specific decrease of SV2A expression levels in the hippocampal glutamatergic neurons but without any epileptic seizures. In this study, we compare the cKO mice with cHZ (Grik4 Cre+/-, SV2A lox/+) and WT (Grik4 Cre+/+, SV2A lox/lox) mice through a battery of tests, used to evaluate different features: the anxiety-related features (Elevated Plus Maze), the locomotor activity (Activity Chambers), the contextual fear-related memory (Contextual Fear Conditioning), and the spatial memory (Barnes Maze). Our results showed statistically significant differences in the habituation to a new environment, an increase in the anxiety levels and spatial memory deficit in the cHZ and cKO groups, compared to the WT group. No statistically significant differences due to the genotype appeared in the spontaneous locomotor activity or the fear-linked memory. However, sexual differences were observed in this last feature. These results highlight not only an important role of the SV2A protein in the cognitive and anxiety problems typically encountered in epileptic patients, but also a possible role in the symptomatology of other neurodegenerative diseases, such as the Alzheimer's disease.

AB - The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose presence is reduced both in animal models and in patients with chronic epilepsy. Besides its implication in the epileptic process, the behavioural consequences of the changes in its expression remain unclear. The purpose of our research is to better understand the possible role(s) of this protein through the phenotype of cKO (Grik4 Cre+/-, SV2A lox/lox) mice, male and female, which present a specific decrease of SV2A expression levels in the hippocampal glutamatergic neurons but without any epileptic seizures. In this study, we compare the cKO mice with cHZ (Grik4 Cre+/-, SV2A lox/+) and WT (Grik4 Cre+/+, SV2A lox/lox) mice through a battery of tests, used to evaluate different features: the anxiety-related features (Elevated Plus Maze), the locomotor activity (Activity Chambers), the contextual fear-related memory (Contextual Fear Conditioning), and the spatial memory (Barnes Maze). Our results showed statistically significant differences in the habituation to a new environment, an increase in the anxiety levels and spatial memory deficit in the cHZ and cKO groups, compared to the WT group. No statistically significant differences due to the genotype appeared in the spontaneous locomotor activity or the fear-linked memory. However, sexual differences were observed in this last feature. These results highlight not only an important role of the SV2A protein in the cognitive and anxiety problems typically encountered in epileptic patients, but also a possible role in the symptomatology of other neurodegenerative diseases, such as the Alzheimer's disease.

KW - Animals

KW - Anxiety/metabolism

KW - Behavior, Animal

KW - Conditioning, Classical

KW - Fear

KW - Female

KW - Hippocampus/metabolism

KW - Male

KW - Maze Learning

KW - Membrane Glycoproteins/metabolism

KW - Memory Disorders/metabolism

KW - Mice, Knockout

KW - Motor Activity

KW - Nerve Tissue Proteins/metabolism

KW - Spatial Memory

U2 - 10.1371/journal.pone.0217882

DO - 10.1371/journal.pone.0217882

M3 - Article

C2 - 31166988

SN - 1932-6203

VL - 14

SP - e0217882

JO - PLoS ONE

JF - PLoS ONE

IS - 6

ER -