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 2012
Externally publishedYes

Fingerprint

Pilocarpine
Neuronal Plasticity
Temporal Lobe Epilepsy
GAP-43 Protein
Neural Cell Adhesion Molecules
Amyloid Precursor Protein Secretases
Nerve Regeneration
Neuropil
Microtubule-Associated Proteins
Amyloid beta-Protein Precursor
Neuropeptide Y
Amyloid Plaques
Temporal Lobe
Amygdala
Amyloid
Peptide Hydrolases
Wounds and Injuries
Brain

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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

BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice. / Yan, Xiao Xin; Cai, Yan; Zhang, Xue Mei; Luo, Xue Gang; Cai, Huaibin; Rose, Gregory M.; Patrylo, Peter R.

In: Experimental Neurology, Vol. 235, No. 1, 05.2012, p. 228-237.

Research output: Contribution to journalArticle

Yan, XX, Cai, Y, Zhang, XM, Luo, XG, Cai, H, Rose, GM & Patrylo, PR 2012, 'BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice', Experimental Neurology, vol. 235, no. 1, pp. 228-237. https://doi.org/10.1016/j.expneurol.2012.01.003
Yan, Xiao Xin ; Cai, Yan ; Zhang, Xue Mei ; Luo, Xue Gang ; Cai, Huaibin ; Rose, Gregory M. ; Patrylo, Peter R. / BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice. In: Experimental Neurology. 2012 ; Vol. 235, No. 1. pp. 228-237.
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