Titre :

LRP1 in GABAergic neurons is a key link between obesity and memory function.

Auteur(s) :

Cristina Da Cruz Rodrigues, K. [Auteur]
Chan Kim, S. [Auteur]
Uner, A. A. [Auteur]
Hou, Z. S. [Auteur]
Young, J. [Auteur]
Campolim, C. [Auteur]
Aydogan, A. [Auteur]
Chung, B. [Auteur]
Choi, A. [Auteur]
Yang, W. M. [Auteur]
Kim, W. S. [Auteur]
Prevot, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Caldarone, B. J. [Auteur]
Lee, H. [Auteur]
Kim, Young Bum [Auteur]
Harvard Medical School [Boston] [HMS]

Titre de la revue :

Molecular metabolism

Nom court de la revue :

Mol Metab

Numéro :

84

Pagination :

101941

Éditeur :

Elsevier

Date de publication :

2024-04-20

ISSN :

2212-8778

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Objective Low-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood–brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric ...
Lire la suite >Objective Low-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood–brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric acid (GABA)ergic neurons causes severe obesity in mice. However, the impact of LRP1 in inhibitory neurons on memory function and cognition in the context of obesity is poorly understood. Methods Mice lacking LRP1 in GABAergic neurons (Vgat-Cre; LRP1loxP/loxP) underwent behavioral tests for locomotor activity and motor coordination, short/long-term and spatial memory, and fear learning/memory. This study evaluated the relationships between behavior and metabolic risk factors and followed the mice at 16 and 32 weeks of age. Results Deletion of LRP1 in GABAergic neurons caused a significant impairment in memory function in 32-week-old mice. In the spatial Y-maze test, Vgat-Cre; LRP1loxP/loxP mice exhibited decreased travel distance and duration in the novel arm compared with controls (LRP1loxP/loxP mice). In addition, GABAergic neuron-specific LRP1-deficient mice showed a diminished capacity for performing learning and memory tasks during the water T-maze test. Moreover, reduced freezing time was observed in these mice during the contextual and cued fear conditioning tests. These effects were accompanied by increased neuronal necrosis and satellitosis in the hippocampus. Importantly, the distance and duration in the novel arm, as well as the performance of the reversal water T-maze test, negatively correlated with metabolic risk parameters, including body weight, serum leptin, insulin, and apolipoprotein J. However, in 16-week-old Vgat-Cre; LRP1loxP/loxP mice, there were no differences in the behavioral tests or correlations between metabolic parameters and cognition. Conclusions Our findings demonstrate that LRP1 from GABAergic neurons is important in regulating normal learning and memory. Metabolically, obesity caused by GABAergic LRP1 deletion negatively regulates memory and cognitive function in an age-dependent manner. Thus, LRP1 in GABAergic neurons may play a crucial role in maintaining normal excitatory/inhibitory balance, impacting memory function, and reinforcing the potential importance of LRP1 in neural system integrity.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-05-06T22:28:57Z
2025-01-22T11:00:50Z