Effects Of Regular Exercise On Cognitive Function And Expression Of Monocarboxylyate Transporter In Brain Of AD Model Mice

Alzheimer’s disease(AD)is a common,progressive development and fatal central nervous system degenerative disease,its pathological change includes tangles(neurofibrillary tangle,NTF),age spots formation(senile plaque,SP)and neuron degeneration lost.Developed progressive cognitive impairment,memory loss and personality changes are often appear in patients,and eventually develop to dementia.Once suffering from the disease,heavy burden will brought to family.While its pathogenesis is not yet clear.Great progress has made in the reasearch of brain protein A beta and protein Tao.It is well known that high energy supply is needed for central nervous system physiological activities,energy metabolism imbalance can affect the normal synapses information transmission,causes degeneration of neurons.In recent years,many scholars explore the pathogenesis of AD and disease processes from the energy metabolism of the central nervous system.Studies have shown that single carboxylic acid such as lactic acid,pyruvic acid and ketone body,playing an important role in energy metabolism.when neurons and glial cells can’t get enough glucose as an energy source material,lactic acid can be used as the energy source of neurons to provide energy to the nervous system.monocarboxylate transporter is a essential carrier for Single carboxylic acid transfer material the present study has been confirmed three subtypes of monocarboxylate transporter in mammalian brain,MCT1,MCT2,MCT4.MCT1,MCT4 mainly expression in astrocytes,whereas MCT2 in neurons,all three together to mediated single carboxylic acid class material transmission between glial cells and neurons,maintain energy metabolism and physiological activities in the brain.Based on this we research the role of MCTs in AD model mice’ learning and memory change via long time and regular aerobic exercise in AD model mice of different months.ObjectThe purpose of this research is to explore MCT1,MCT2 and MCT4 expression changes in AD model mouse,and the impact on the learning and memory ability from the perspective of energy metabolism.Method2,6,8 months AD mice known as APP/PS1 transgenic mice and WT mice(C57BL/6J)which are forced to swim for eight weeks exercises are taken as treatment groups,while,4,8,10 months AD mice and WT mice which are not swimming trained are regarded as controls.Morris water maze is performed for behavioral tests,including the hidden platform and space exploration experiments.Then we determine the protein expression of MCT1、MCT2、MCT4 in brain using western-blot,meanwhile,immunohistochemistry is used to measure the level of MCT1、MCT2、MCT4 in cerebral cortex and hippocampus,respectively.Results(1)For behavioral tests by Mirrors: the hidden platform experiment shows that the average escape latency and escape distance is reduced significantly of eight-weekswimming-trained mice compared to the controls at the first two days(P<0.05),and a conspicuous increase of duration at the target quadrant within 60 s of treatment mice is detected by space exploration experiment,as well as,compared to the controls(P<0.05);(2)For protein expression by western-blot: we determined the protein expression of MCTs levels in brain,results showed that the MCTs levels of swimming-trained mice are increased in a big degree,inversely,the MCTs level of non-swimming-trained mice(controls)do not(P<0.05).(3)For immunohistochemical,the expressions of MCT1 and MCT4 are increased in treatment mice(P<0.05),however,there is no significant difference in the level of MCT2 between the treatment and control mice.ConclusionsOur findings demonstrate that the regular long-term aerobic exercises are able to increase the expression of MCTs in the brain of AD mice,as well as improving the state of energy metabolism in the central nervous system and enhancing the cognitive function.