title: BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice.
abstract: The brain is capable of remarkable synaptic reorganization following stress and injury, often using the same molecular machinery that governs neurodevelopment. This form of plasticity is crucial for restoring and maintaining network function. However, neurodegeneration and subsequent reorganization can also play a role in disease pathogenesis, as is seen in temporal lobe epilepsy and Alzheimer's disease. β-Secretase-1 (BACE1) is a protease known for cleaving β-amyloid precursor protein into β-amyloid (Aβ), a major constituent in amyloid plaques. Emerging evidence suggests that BACE1 is also involved with synaptic plasticity and nerve regeneration. Here we examined whether BACE1 immunoreactivity (IR) was altered in pilocarpine-induced epileptic CD1 mice in a manner consistent with the synaptic reorganization seen during epileptogenesis. BACE1-IR increased in the CA3 mossy fiber field and dentate inner molecular layer in pilocarpine-induced epileptic mice, relative to controls (saline-treated mice and mice 24-48 h after pilocarpine-status), and paralleled aberrant expression of neuropeptide Y. Regionally increased BACE1-IR also occurred in neuropil in hippocampal area CA1 and in subregions of the amygdala and temporal cortex in epileptic mice, colocalizing with increased IR for growth associated protein 43 (GAP43) and polysialylated-neural cell adhesion molecule (PSA-NCAM), but reduced IR for microtubule-associated protein 2 (MAP2). These findings suggest that BACE1 is involved in aberrant limbic axonal sprouting in a model of temporal lobe epilepsy, warranting further investigation into the role of BACE1 in physiological vs. pathological neuronal plasticity.
authors.affiliation: Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan 410013, China. yanxiaoxin@csu.edu.cn
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Xue-Gang
authors.initials: XG
authors.lastname: Luo
authors.forename: Huaibin
authors.initials: H
authors.lastname: Cai
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Rose
authors.forename: Peter R
authors.initials: PR
authors.lastname: Patrylo
mesh_terms: D000679:Amygdala / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D056654:CA3 Region, Hippocampal / Q000378:metabolism* / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010862:Pilocarpine; D013702:Temporal Lobe / Q000378:metabolism
chemical_list: D010862:Pilocarpine; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse