| Dopamine(DA)is a catecholamine neurotransmitter,which is highly conserved during evolution.Tyrosine hydroxylase(TH),the enzyme which catalyzes the first and rate limiting step in dopamine biosynthesis,can be used as a specific markers of dopaminergic neurons to determine the distribution pattern of dopaminergic neurons.?-Methyl-DL-tyrosine(?-MT)is an effective inhibitor of tyrosine hydroxylase,which reduce dopamine level in the brain by competitive inhibition.Changes of dopamine signal are related closely to human neurodegenerative diseases such as Parkinson's disease(PD).PD is a kind of typical neurodegenerative disease which often accompanied by symptoms such as tremor and bradykinesia.Drosophila melanogaster has contributed significantly to the understanding of disease mechanisms in PD.However,there have been contradictory results from a number of reports regarding the loss of dopaminergic neurons in PD Drosophila melanogaster models.In this experiment,we use Drosophila melanogaster as the experimental materials,which is a classic model of biological.Drosophila melanogaster were fed ?-MT at concentration of 0.5mM,0.75 mM and 1.0mM and were compared to the normal wild flies in growth and negative geotaxis.We use immunohistochemistry technology to determine the distribution of TH in the brain of Drosophila melanogaster and infer the physiological function of dopaminergic neurons in different brain regions.The results show that the deficiency of TH positive neurons in the brain of Drosophila melanogaster caused by ?-MT influences physiological activity significantly.This influence is mainly as follows.?-MT produces inhibition effects on the growth and development of Drosophila melanogaster,which cause its growth cycle extended gradually along with increasing concentration of ?-MT,embryo survival rate and pupa rate and the number of adult flies are reduced at the same time.During pupation,overall pupation trends of different concentrations of experimental groups is same as the control group,but the effects of different concentrations of ?-MT on the length of pupa were not significant(P= 0.189).The Drosophila melanogaster treated with ?-MT show a significant decrease in negative geotaxis,accompany with the symptoms of PD such as wings tremor and rotational behavior.Compared to the control group,the experimental group have significant difference extremely in the average number of Drosophila melanogaster through the marking of device(P < 0.01).We find varying degrees of deficiency of TH positive neurons at different concentrations.Immunohistochemical reaction shows a deletion of PPL1 cluster which distribute in the lateral posterior protocerebral inDrosophila melanogaster of concentration 1.0m M.Drosophila melanogaster treated with different concentrations of inhibitors has varying degrees of deletions of PAM cluster in perineurium along with an increase in drug concentration.Clusters and immunoreactive fibers projected in the optic lobe show significant deletion along with inhibitor concentrations.We speculate PPL1 cluster might be related to the activity of Drosophila melanogaster and PAM cluster might regulate the growth and development as neurohormonal.The dopaminergic neurons in optic lobe might play an important role in achieving their biological function as neurotransmitters and neural conditioning.In this experiment,we constructed the Drosophila melanogaster model of Parkinson's disease to study the effect of ?-MT on tyrosine hydroxylase level in the brain and behavior of Drosophila melanogaster,which reveals the relationship between locomotor activity and dopaminergic neurons.We could infer the function of dopaminergic neurons in different regions of Drosophila melanogaster's brain.This experiment provide some theoretical data to neurological diseases(such as PD)caused by the loss of dopaminergic neurons for further study. |
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