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Sequential expression of cell‐cycle regulators and Alzheimer's disease–related proteins in entorhinal cortex after hippocampal excitotoxic damage
Author(s) -
HernándezOrtega Karina,
Ferrera Patricia,
Arias Clorinda
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21301
Subject(s) - dentate gyrus , entorhinal cortex , hippocampal formation , neuroscience , hippocampus , biology , kainic acid , neurodegeneration , cell cycle , cyclin , microbiology and biotechnology , cell , medicine , glutamate receptor , disease , pathology , receptor , biochemistry
Growing evidence suggests that one of the earliest events in the neuronal degeneration of Alzheimer's disease (AD) is aberrant cell‐cycle activation in postmitotic neurons, which may, in fact, be sufficient to initiate the neurodegenerative cascade. In the present study we examined whether cyclins and cyclin‐dependent kinases, molecules normally associated with cell‐cycle control, may be involved in delayed expression of altered Alzheimer's proteins in two interconnected areas, the entorhinal cortex (EC) and the dentate gyrus (DG), after a hippocampal excitotoxic lesion. Several cell‐cycle proteins of the G 1 and S phases and even of the G 2 phase were found to be up‐regulated in the EC after kainic acid evoked neuronal death in the hippocampus. In addition, we describe the progressive expression of two Alzheimer's‐related proteins, PHF‐1 and APP, which reached higher levels immediately after the increase in G 1 /S‐phase markers. Hence, the results of the present study support the participation of cell‐cycle dysregulation as a key component of the process that may ultimately lead to expression of AD proteins and neuronal death in a brain area when the target site for synaptic inputs in that area is damaged by an excitotoxic insult. © 2007 Wiley‐Liss, Inc.