Acute Impairment of Mitochondrial Trafficking by beta-Amyloid Peptides in Hippocampal Neurons

Defects in axonal transport are often associated with a wide variety of neurological diseases including Alzheimer's disease (AD). Beta-amyloid (Abeta) is a major component of neuritic plaques associated with pathological conditions of AD brains. Here, we report that a brief exposure of cultured...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 2006-10, Vol.26 (41), p.10480-10487
Main Authors: Rui, Yanfang, Tiwari, Priyanka, Xie, Zuoping, Zheng, James Q
Format: Article
Language:English
Subjects:
Amyloid beta-Peptides - metabolism
Amyloid beta-Peptides - pharmacology
Animals
Cell Death - drug effects
Cell Death - physiology
Cells, Cultured
Hippocampus - drug effects
Hippocampus - metabolism
Hippocampus - pathology
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondria - pathology
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Peptides - metabolism
Peptides - pharmacology
Protein Transport - drug effects
Protein Transport - physiology
Rats
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Defects in axonal transport are often associated with a wide variety of neurological diseases including Alzheimer's disease (AD). Beta-amyloid (Abeta) is a major component of neuritic plaques associated with pathological conditions of AD brains. Here, we report that a brief exposure of cultured hippocampal neurons to Abeta molecules resulted in rapid and severe impairment of mitochondrial transport without inducing apparent cell death and significant morphological changes. Such acute inhibition of mitochondrial transport was not associated with a disruption of mitochondria potential nor involved aberrant cytoskeletal changes. Abeta also did not elicit significant Ca2+ signaling to affect mitochondrial trafficking. However, stimulation of protein kinase A (PKA) by forskolin, cAMP analogs, or neuropeptides effectively alleviated the impairment. We also show that Abeta inhibited mitochondrial transport by acting through glycogen synthase kinase 3beta (GSK3beta). Given that mitochondria are crucial organelles for many cellular functions and survival, our findings thus identify an important acute action of Abeta molecules on nerve cells that could potentially contribute to various abnormalities of neuronal functions under AD conditions. Manipulation of GSK3beta and PKA activities may represent a key approach for preventing and alleviating Abeta cytotoxicity and AD pathological conditions.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.3231-06.2006