A novel mechanism for endogenous formaldehyde elevation in SAMP8 mouse.

Abstract

Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people worldwide. Increasing evidence suggests that formaldehyde might be one of the various pathological mechanisms involved in the process of AD onset. Here, we use an AD mouse model, senescence accelerated mouse-prone 8 strain (SAMP8), to study the relationship between endogenous formaldehyde and impairment of cognition. The Morris water maze test was used to evaluate the spatial learning and memory ability of 3-month-old SAMP8 mice, and we correlated the results with endogenous formaldehyde concentrations in the brain. To investigate the underlying reasons for formaldehyde elevation in neurodegenerative diseases, the expression levels of enzymes involved in formaldehyde metabolism were analyzed, including (anabolic) semicarbazide sensitive amine oxidase (SSAO) and (catabolic) alcohol dehydrogenase III (ADH3). When compared with age-matched SAMR1 mice, we found that in 3-month-old SAMP8 mice the capacity for spatial learning and memory was lower, while brain formaldehyde levels were higher. By using real-time PCR, western blotting, enzyme assay, and immunohistochemistry techniques, we discovered that SSAO expression levels were increased, whereas ADH3 exhibited reduced expression levels of mRNA, protein, and enzyme activity. The imbalance of these metabolic enzymes may represent a causal explanation for the observed formaldehyde elevation in the SAMP8 brain. Such increase could be responsible for the observed tau hyperphosphorylation assumed to result in protein aggregation, ultimately leading to cognitive impairment. Taken together, our study gives new insights into the role of metabolic enzymes in age-related accumulation of formaldehyde, and thus the establishment of neurodegenerative diseases.

• Authors: Min Qiang, Rong Xiao, Tao Su, Bei-Bei Wu, Zhi-Qian Tong, Ying Liu, Rong-Qiao He
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 40 Issue 4 Pg. 1039-53 ( 2014) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 24583407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arabidopsis Proteins
• Cell Adhesion Molecules
• tau Proteins
• Formaldehyde
• ADH1C protein, human
• Alcohol Dehydrogenase
• ALDH2 protein, mouse
• Aldehyde Dehydrogenase
• Aldehyde Dehydrogenase, Mitochondrial
• Amine Oxidase (Copper-Containing)
• semicarbazide-sensitive amine oxidase-vascular adhesion protein-1, mouse
• Intramolecular Transferases
• marneral synthase, Arabidopsis

Topics

• Aging (genetics, metabolism)
• Alcohol Dehydrogenase (metabolism)
• Aldehyde Dehydrogenase (metabolism)
• Aldehyde Dehydrogenase, Mitochondrial
• Alzheimer Disease (complications)
• Amine Oxidase (Copper-Containing)
• Animals
• Arabidopsis Proteins
• Brain (metabolism)
• Cell Adhesion Molecules
• Chromatography, High Pressure Liquid
• Cognition Disorders (etiology, metabolism, pathology)
• Disease Models, Animal
• Formaldehyde (metabolism)
• Intramolecular Transferases
• Liver (metabolism)
• Male
• Mice
• Time Factors
• tau Proteins (metabolism)