Expression Of TRPC Channels In The A?-Induced Alzheimer's Disease Mice

Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive cognitive decline in clinical.The typical pathological features of AD are Senile plaques of which the core is P-amyloid protein(A?),neurofibrillary tangles and death of neurons.A? deposition is currently recognized as the final pathway for AD formation.At the same time,calcium homeostasis disorder can change the structure and function of neurons,and even lead to irreversible neuronal damage.In recent years,studies found the canonical transient receptor potential(TRPC)channels,non-selective calcium channels located on the cell membrane,are highly expressed in brain neurons.Meanwhile the relative researches show that TRPC channels are involved in proliferation,differentiation,apoptosis,degeneration and synaptic plasticity in nervous system.However,the expression and functional mechanism of TRPC channels are still not clear in AD mouse model induced by A?.ObjectiveTo investigate the protein expression of the TRPC channels in the hippocampus of A? induced AD mice.Methods1.Five weeks age male ICR 36 mice were fed for 5 days and were randomly divided into AD group and control group with 18 mice in each group.2.AD mice models were established by A? 1-42 micro injection into the lateral intracerebroventricular.Learning and memory abilities of the mice were determined using navigation and space exploration experiment of Morris water maze after ten days' intracerebroventricular injections.Animals were killed after behavior examination.All TRPC1?TRPC7 mRNA levels in the hippocampus of the mice were detected using reverse transcriptase polymerase chain reaction(RT-PCR).Hippocampal TRPC4 protein expression was examined using immunofluorescence and Western blot methods.Results1.Morris water maze test results showed that,from the third day on,the escape latency of AD group was longer than that of the control group(P<0.05),the swimming distance to find a platform was longer than that of the control group in the navigation experiment(P<0.05),the target quadrant occupancy of AD group was significantly shortened(P<0.01)and the frequency of platform crossing of AD group was significantly reduced in the space exploration experiment(P<0.01).2.RT-PCR results showed that all TRPC channels(TRPC1?TRPC7)mRNA were expressed in the hippocampal of both AD group and control group.Among these channels,only TRPC4 mRNA levels of AD group were significantly higher than that of the control group(P<0.01).3.Immunofluorescence images showed that TRPC4 channel expressed on the membrane of neurons and the intensities of the immunofluorescence of TRPC4 in AD group were stronger than that of control group.4.Western blot results showed that the TRPC4 channel protein expression of AD group were higher than that of control group(P<0.05).ConclusionAfter intracerebroventricular injection of A?1-42 oligomers,learning and memory abilities of mice were weakened,the expression of protein and mRNA of TRPC4 channel on hippocampal neurons were increased.These suggest that TRPC channels may be involved in the pathogenesis of AD induced by A? deposition.