Memory Impairment Induced by Borna Disease Virus 1 Infection is Associated with Reduced H3K9 Acetylation.
Cell Physiol Biochem
; 49(1): 381-394, 2018.
Article
en En
| MEDLINE
| ID: mdl-30138929
ABSTRACT
BACKGROUND/AIMS:
Borna disease virus 1 (BoDV-1) infection induces cognitive impairment in rodents. Emerging evidence has demonstrated that Chromatin remodeling through histone acetylation can regulate cognitive function. In the present study, we investigated the epigenetic regulation of chromatin that underlies BoDV-1-induced cognitive changes in the hippocampus.METHODS:
Immunofluorescence assay was applied to detect BoDV-1 infection in hippocampal neurons and Sprague-Dawley rats models. The histone acetylation levels both in vivo and vitro were assessed by western blots. The acetylation-regulated genes were identified by ChIP-seq and verified by RT-qPCR. Cognitive functions were evaluated with Morris Water Maze test. In addition, Golgi staining, and electrophysiology were used to study changes in synaptic structure and function.RESULTS:
BoDV-1 infection of hippocampal neurons significantly decreased H3K9 histone acetylation level and inhibited transcription of several synaptic genes, including postsynaptic density 95 (PSD95) and brain-derived neurotrophic factor (BDNF). Furthermore, BoDV-1 infection of Sprague Dawley rats disrupted synaptic plasticity and caused spatial memory impairment. These rats also exhibited dysregulated hippocampal H3K9 acetylation and decreased PSD95 and BDNF protein expression. Treatment with the HDAC inhibitor, suberanilohydroxamic acid (SAHA), attenuated the negative effects of BoDV-1.CONCLUSION:
Our results demonstrate that regulation of H3K9 histone acetylation may play an important role in BoDV-1-induced memory impairment, whereas SAHA may confer protection against BoDV-1-induced cognitive impairments. This study finds important mechanism of BoDV-1 infection disturbing neuronal synaptic plasticity and inducing cognitive dysfunction from the perspective of histone modification.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Borna
/
Virus de la Enfermedad de Borna
/
Histonas
/
Memoria
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Physiol Biochem
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China