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β‐secretase expression in normal and functionally deprived rat olfactory bulbs: Inverse correlation with oxidative metabolic activity
Author(s) -
Yan XiaoXin,
Xiong Kun,
Luo XueGang,
Struble Robert G.,
Clough Richard W.
Publication year - 2007
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21239
Subject(s) - olfactory bulb , biology , biochemistry , oxidative phosphorylation , synapse , premovement neuronal activity , microbiology and biotechnology , amyloid precursor protein , neuroscience , alzheimer's disease , medicine , central nervous system , disease
Cerebral hypometabolism, mitochondrial dysfunction, and β‐amyloid peptide (Aβ) accumulation are well‐characterized manifestations of Alzheimer's disease (AD). β‐Secretase (BACE) is a prerequisite for amyloidogenesis, and it is up‐regulated in sporadic AD. To explore a potential in vivo mechanism by which Aβ production is modulated by neuronal activity and/or oxidative metabolism, we compared BACE expression with cytochrome c oxidase (CO) or succinic dehydrogenase (SDH) activity in normal and functionally deprived adult rat olfactory bulb. In normal bulb, BACE was expressed predominantly in the glomerular layer, but labeling intensity within individual glomeruli varied substantially. A strong negative correlation existed between BACE labeling intensity and CO or SDH activity among individual glomeruli. Unilateral naris occlusion resulted in elevated glomerular BACE labeling in the deprived bulbs relative to the nondeprived counterparts, which was correlated with decreased CO activity in the same anatomic location. Enhanced BACE labeling was confirmed by measurements of elevated protein levels, enzymatic activity, and β‐site cleavage products of amyloid precursor protein in bulb extracts. Our findings reveal a negative regulation of BACE expression by physiological neuronal activity and an intrinsic inverse correlation between BACE expression and oxidative metabolism at the first synapse on the olfactory pathway. The results point to a biological role of BACE in synapse function and plasticity as well as a potential mechanism whereby reduced neuronal activity or metabolism could lead to amyloid overproduction in synaptic terminals. J. Comp. Neurol. 501:52–69, 2007. © 2007 Wiley‐Liss, Inc.