A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer's mouse model.

ABSTRACT:

Introduction

Tropomyosin related kinase B (TrkB) and C (TrkC) receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid beta (Aβ) toxicity. Upregulating TrkB/C signaling could reduce Alzheimer's disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction.

Methods

PTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APP^L/S) and wild-type controls. Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA sequencing.

Results

In APP^L/S mice, BD10-2 treatment improved memory and LTP deficits. Th

SUBMITTER: Latif-Hernandez A 

PROVIDER: S-EPMC11247716 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature