Increased Hippocampal ProBDNF Contributes to Memory Impairments in Aged Mice

Area of Science:

• Neuroscience
• Molecular Biology
• Aging Research

Background:

• Cognitive decline during aging and neurodegenerative diseases is a significant health concern.
• Neurotrophins, including Brain-Derived Neurotrophic Factor (BDNF) and its precursor proBDNF, are implicated in cognitive aging.
• ProBDNF and mature BDNF have opposing effects on neuronal function and plasticity.

Purpose of the Study:

• To investigate the role of increased proBDNF levels in aging-related memory impairments.
• To determine the impact of proBDNF on hippocampal function and spatial memory performance.

Main Methods:

• Biochemical analysis of hippocampal proBDNF levels in young versus aged mice.
• Intra-hippocampal infusions of proBDNF or a p75NTR antagonist (TAT-Pep5) in male mice trained on the water radial arm maze (WRAM).
• Assessment of memory performance and analysis of p-cofilin levels.

Main Results:

• Aged mice exhibited higher hippocampal proBDNF levels, inversely correlating with WRAM performance.
• Infusion of proBDNF into the hippocampus of well-performing aged mice significantly impaired memory.
• This impairment was linked to increased p-cofilin levels.
• Infusion of TAT-Pep5 in poor-performing aged mice significantly improved learning and memory.

Conclusions:

• Increased proBDNF levels contribute to aging-related memory deficits in the hippocampus.
• The p75 Neurotrophin Receptor (p75NTR) pathway is involved in these proBDNF-mediated memory impairments.
• Targeting the proBDNF/p75NTR interaction may offer therapeutic strategies for cognitive decline.