title: Valproic acid ameliorates olfactory dysfunction in APP/PS1 transgenic mice of Alzheimer's disease: Ameliorations from the olfactory epithelium to the olfactory bulb.
abstract: Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Alzheimer's disease (AD) and mild cognitive impairment, pointing to the progression to dementia. Recent studies have revealed that valproic acid (VPA) has neuroprotective effects in rodent models of AD. In this study, we investigated the effects of VPA on olfactory dysfunction of APP/PS1 double transgenic mouse models of AD. After continuous treatment with a 100mg/kg daily dose of VPA for 3 months, APP/PS1 mice showed improved olfactory performances. In agreement with the behavioral findings, VPA treatment reduced amyloid β (Aβ) burden in the olfactory epithelium (OE) of transgenic mice. And, VPA increased epithelial thickness of the olfactory mucosa through decreased cell apoptosis and increased cell proliferation. In the olfactory bulb (OB), VPA administration also reduced senile plaques and levels of soluble and insoluble Aβ42 peptides. Besides, VPA promoted the increase of mitral cells and decrease of neurofilament immunostaining. In hence, VPA treatment completely improved the olfactory performances and prevented degenerative changes of the OE and OB. Our study raises the possibility of AD diagnosis by OE biopsy. Moreover, VPA may provide a novel therapeutic strategy for the treatment of olfactory dysfunction in AD patients.
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Yao
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Jing
authors.affiliation: Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Building 6, Anhui Jianxi District, Luoyang 471003, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Lv
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Li
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Feng-Feng
authors.initials: FF
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Xi-Chao
authors.initials: XC
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Ye-Jun
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.
authors.forename: Miao-Qing
authors.initials: MQ
authors.lastname: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D051379:Mice; D009830:Olfactory Bulb / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics*; D012678:Sensation Disorders / Q000517:prevention & control*; D012903:Smell / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D014635:Valproic Acid
keywords: APP/PS1 transgenic mice; Alzheimer's disease; Amyloid β; Olfactory system