Brain Regions Thiamine Lack Of AD Model Mouse Neuronal Mitochondrial Function

Alzheimer’s disease(Alzheimer’s disease, AD), is the most common neurodegenerative disease, the main pathologic feature is extensive loss of neurons and synapses, neurofibrillary tangles(NFTs) and senile plaques(SPs) aggregation. Because the insidious onset of Alzheimer’s disease and the slow progression, it is difficult to detect in early time.Then it gradually showing memory loss, cognitive disorders and other symptoms as the main feature.Pathogenesis of AD etiology is unclear, there are many hypotheses, previous studies mainly in AD amyloid cascade hypothesis, based on recent energy metabolism and AD pathogenesis of widespread concern researchers. Positron tomography, the researchers found that many patients with AD in the typical clinical symptoms and pathological changes before the brain has appeared abnormal glucose metabolism, suggesting decreased mitochondrial function, energy metabolism may be an early signal attenuation AD pathogenesis. Mitochondria may involved in the development of AD through a variety of mechanisms, including the mitochondrial outer membrane protein, the voltage-dependent anion channel protein 1(VDAC1), can be directly related to Aβ and tau protein phosphorylation effect, mitochondrial pore opening and closing, interference ATP / ADP normal transport and other metabolites, resulting in mitochondrial dysfunction, and cytochrome C(Cytochrome C) is the electron transport chain, only the outer periphery of the protein is located inside of the outer membrane of mitochondria, closely associated with apoptosis.That thiamine vitamin B1, vitamin B1 deficiency when(Thiamine Deficiency, TD) can lead to neuronal death in specific regions of the brain. Such as the thalamus, midbrain, brainstem, and cerebellum, and selective cell death, inflammation, proliferation of glial cells and oxidative metabolism imbalance is a common feature of many age-related neurodegenerative diseases, such as AD, PD, etc; Vitamin B1 the absence, in the nerve tissue, under normal circumstances, mainly by aerobic decomposition of sugar for energy, this time due to insufficient energy supply, the nucleic acid synthesis and myelin in the pentose phosphate metabolism is affected, can also affect the nerve myelin membrane phospholipid synthesis, resulting in peripheral neuritis and other neurological diseases. Experiments by APP / PS1 mice and WT mice hippocampus and frontal cortex area positioning injection of vitamin B1 antagonist and Na Cl, after 30 days feeding TD treatment, take brain perfusion, do RT-PCR and Western Blot using fresh tissue examination, some tissue sections for VDAC1 and cytochrome C immunofluorescence double staining. When several ways to explore the above effects on mitochondrial function in neurons when thiamine deficiency, and in the expression of mitochondrial function related trend two proteins, provide a theoretical basis for the relevant clinical treatment. Objective:Detect the expression of voltage-dependent anion channel protein 1(VDAC1) and cytochrome C(Cytochrome C) protein after The thiamine deficiency of brain regions of the AD model mice. Methods:According to the mouse brain atlas, stereotactic injected the pyrithiamine on the right dentate gyrus and prefrontal cortex brain regions which is in the 2-3 months wild type C57BL/6 and Alzheimer’s disease transgenic mice to establish a kind of brain region TD models. Ten days after TD treating, the mice were tested through ethology. Thirty days After TD treating we observed the morphology features and the expression of VDAC1 and Cytochrome C protein within the target brain region by immunofluorescence, Western-blot and RT-PCR. Results:After TD treating, the active and passive avoidance tests decreased significantly compared with the sham group(p<0.05), and there is a high expression of the VDAC1 and Cytochrome C protein in the brain region of both kind of mice(p<0.05). Also, the mt DNA of the brain tissue increased(p<0.05). Conclusion:Thiamine deficiency can lead to the mitochondrial function changes on the brain of AD model mice and wild-type mouse.