Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease

Rugao Liu, Joy X. Lei, Chun Luo, Xun Lan, Liying Chi, Panyue Deng, Saobo Lei, Othman Ghribi, Qing Yan Liu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Though loss of function in CBP/p300, a family of CREB-binding proteins, has been causally associated with a variety of human neurological disorders, such as Rubinstein-Taybi syndrome, Huntington's disease and drug addiction, the role of EP300 interacting inhibitor of differentiation 1 (EID1), a CBP/p300 inhibitory protein, in modulating neurological functions remains completely unknown. Through the examination of EID1 expression and cellular distribution, we discovered that there is a significant increase of EID1 nuclear translocation in the cortical neurons of Alzheimer's disease (AD) patient brains compared to that of control brains. To study the potential effects of EID1 on neurological functions associated with learning and memory, we generated a transgenic mouse model with a neuron-specific expression of human EID1 gene in the brain. Overexpression of EID1 led to an increase in its nuclear localization in neurons mimicking that seen in human AD brains. The transgenic mice had a disrupted neurofilament organization and increase of astrogliosis in the cortex and hippocampus. Furthermore, we demonstrated that overexpression of EID1 reduced hippocampal long-term potentiation and impaired spatial learning and memory function in the transgenic mice. Our results indicated that the negative effects of extra nuclear EID1 in transgenic mouse brains are likely due to its inhibitory function on CBP/p300 mediated histone and p53 acetylation, thus affecting the expression of downstream genes involved in the maintenance of neuronal structure and function. Together, our data raise the possibility that alteration of EID1 expression, particularly the increase of EID1 nuclear localization that inhibits CBP/p300 activity in neuronal cells, may play an important role in AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)902-912
Number of pages11
JournalNeurobiology of Disease
Volume45
Issue number3
DOIs
StatePublished - Mar 1 2012

Fingerprint

Neuronal Plasticity
Alzheimer Disease
Transgenic Mice
Brain
Neurons
p300-CBP Transcription Factors
Rubinstein-Taybi Syndrome
CREB-Binding Protein
Intermediate Filaments
Long-Term Potentiation
Huntington Disease
Acetylation
Nervous System Diseases
Histones
Substance-Related Disorders
Hippocampus
Maintenance
Learning
Gene Expression
Genes

Keywords

  • Acetylation
  • Alzheimer's disease
  • CBP/p300
  • EP300 interacting inhibitor of differentiation 1
  • Histone
  • P53

ASJC Scopus subject areas

  • Neurology

Cite this

Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease. / Liu, Rugao; Lei, Joy X.; Luo, Chun; Lan, Xun; Chi, Liying; Deng, Panyue; Lei, Saobo; Ghribi, Othman; Liu, Qing Yan.

In: Neurobiology of Disease, Vol. 45, No. 3, 01.03.2012, p. 902-912.

Research output: Contribution to journalArticle

Liu, Rugao ; Lei, Joy X. ; Luo, Chun ; Lan, Xun ; Chi, Liying ; Deng, Panyue ; Lei, Saobo ; Ghribi, Othman ; Liu, Qing Yan. / Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease. In: Neurobiology of Disease. 2012 ; Vol. 45, No. 3. pp. 902-912.
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