Received for publication May 20, 2008.
Revised July 9, 2008.
Accepted for publication July 9, 2008.

The extensive nitration of neurofilament light chain in the hippocampus is associated with the cognitive impairment induced by amyloid beta in mice

Abstract

Tyrosine nitration of proteins at an extensive level is widely associated with cognitive pathology induced by amyloid beta (A). The precise identity and the explicit consequences of the protein nitration, however, have scarcely been addressed. In this study, we examined the detectable nitration of proteins in the hippocampus of mice with cognitive impairment (Day 5) induced by the i.c.v.-injection of A_25-35 (Day 0). The intensity of nitration of proteins was inversely associated with the level of recognition memory in mice. The detectable tyrosine nitrations were revealed in proteins with a single size of approximately 70 kDa. The specific nitrated proteins at this size were identified utilizing the liquid chromatography / mass spectrometry / mass spectrometry analysis and immunodetection methods. Neurofilament light chain (NFL) was found intensely nitrated. Increased nitration of NFL was associated with its serine hyperphosphorylation and weak interaction with the nuclear distribution element-like (NUDEL), an essential protein for the stable assembly of neurofilaments. No changes in cell numbers in the hippocampus were found (Day 5) in A_25-35-injected mice. These findings suggested that extensive nitration of NFL is associated with the A-induced impairment of recognition memory in mice.

Key words: Amyloid beta, Neurofilament light chain, Recognition memory, Serine phosphorylation, Tyrosine nitration, mouse