BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice

Xiao Xin Yan, Yan Cai, Xue Mei Zhang, Xue Gang Luo, Huaibin Cai, Gregory M. Rose, Peter R. Patrylo

    Research output: Contribution to journalArticle

    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.

    Original languageEnglish (US)
    Pages (from-to)228-237
    Number of pages10
    JournalExperimental Neurology
    Volume235
    Issue number1
    DOIs
    StatePublished - May 1 2012

    Keywords

    • Aberrant neuroplasticity
    • Alzheimer's disease
    • Beta-secretase
    • Dystrophic neurites
    • Mossy fiber sprouting
    • Temporal lobe epilepsy

    ASJC Scopus subject areas

    • Neurology
    • Developmental Neuroscience

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  • Cite this

    Yan, X. X., Cai, Y., Zhang, X. M., Luo, X. G., Cai, H., Rose, G. M., & Patrylo, P. R. (2012). BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice. Experimental Neurology, 235(1), 228-237. https://doi.org/10.1016/j.expneurol.2012.01.003