Valproic acid ameliorates olfactory dysfunction in APP/PS1 transgenic mice of Alzheimer's disease: Ameliorations from the olfactory epithelium to the olfactory bulb. 2016

Zhi-Gang Yao, and Hai-Yan Jing, and Dong-Mei Wang, and Bei-Bei Lv, and Jia-Mei Li, and Feng-Feng Liu, and Hui Fan, and Xi-Chao Sun, and Ye-Jun Qin, and Miao-Qing Zhao
Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250021, China.

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.

UI MeSH Term Description Entries
D009830 Olfactory Bulb Ovoid body resting on the CRIBRIFORM PLATE of the ethmoid bone where the OLFACTORY NERVE terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose DENDRITES the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the VOMERONASAL ORGAN via the vomeronasal nerve, is also included here. Accessory Olfactory Bulb,Olfactory Tract,Bulbus Olfactorius,Lateral Olfactory Tract,Main Olfactory Bulb,Olfactory Glomerulus,Accessory Olfactory Bulbs,Bulb, Accessory Olfactory,Bulb, Main Olfactory,Bulb, Olfactory,Bulbs, Accessory Olfactory,Bulbs, Main Olfactory,Bulbs, Olfactory,Glomerulus, Olfactory,Lateral Olfactory Tracts,Main Olfactory Bulbs,Olfactorius, Bulbus,Olfactory Bulb, Accessory,Olfactory Bulb, Main,Olfactory Bulbs,Olfactory Bulbs, Accessory,Olfactory Bulbs, Main,Olfactory Tract, Lateral,Olfactory Tracts,Olfactory Tracts, Lateral,Tract, Lateral Olfactory,Tract, Olfactory,Tracts, Lateral Olfactory,Tracts, Olfactory
D009831 Olfactory Mucosa That portion of the nasal mucosa containing the sensory nerve endings for SMELL, located at the dome of each NASAL CAVITY. The yellow-brownish olfactory epithelium consists of OLFACTORY RECEPTOR NEURONS; brush cells; STEM CELLS; and the associated olfactory glands. Olfactory Epithelium,Olfactory Membrane,Epithelium, Olfactory,Membrane, Olfactory,Membranes, Olfactory,Mucosa, Olfactory,Olfactory Membranes
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012678 Sensation Disorders Disorders of the special senses (i.e., VISION; HEARING; TASTE; and SMELL) or somatosensory system (i.e., afferent components of the PERIPHERAL NERVOUS SYSTEM). Sensory Disorders,Special Senses Disorders,Sensation Disorder,Senses Disorder, Special,Senses Disorders, Special,Sensory Disorder,Special Senses Disorder
D012903 Smell The ability to detect scents or odors, such as the function of OLFACTORY RECEPTOR NEURONS. Olfaction,Sense of Smell,Smell Sense
D014635 Valproic Acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS. Dipropyl Acetate,Divalproex,Sodium Valproate,2-Propylpentanoic Acid,Calcium Valproate,Convulsofin,Depakene,Depakine,Depakote,Divalproex Sodium,Ergenyl,Magnesium Valproate,Propylisopropylacetic Acid,Semisodium Valproate,Valproate,Valproate Calcium,Valproate Sodium,Valproic Acid, Sodium Salt (2:1),Vupral,2 Propylpentanoic Acid
D016564 Amyloid beta-Protein Precursor A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES. Amyloid A4 Protein Precursor,Amyloid Protein Precursor,beta-Amyloid Protein Precursor,Amyloid beta Precursor Protein,Protease Nexin 2,Protease Nexin II,Amyloid beta Protein Precursor,Nexin 2, Protease,Nexin II, Protease,beta Amyloid Protein Precursor,beta-Protein Precursor, Amyloid
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053764 Presenilin-1 Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans. Presenilin 1,S182 Protein

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