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

• DOI: 10.1016/j.molmet.2024.101941
• Publication Date: 2024-04-16T17:50:08Z
• Authors: Kellen Cristina d...; Seung Chan Kim; Aaron Aykut Uner; Zhi-Shuai Hou; Jennie Young; Clara Campolim; Ahmet Aydogan; Brendon Chung; Anthony Choi; Won-Mo Yang; Woojin S. Kim; Vincent Prevot; Barbara J. Caldarone; Hyon Lee; Young-Bum Kim
• Keywords: LRP1; Link (geometry)

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