Taclo Striatum Stereotactic Injection Mediated Rats’Neurobehavioral Changes And Cox-2Expression In Substantia Nigra

Background Parkinson disease (PD) is a common neurodegenerative disease, whose severity is related to the injury of dopaminergic neurons in substantia nigra. So far, there is hardly any medicine that can inhibit PD’ s pathological process effectively. The etiology of PD remains unclear so far, but environmental toxicants may be one of the main causes. Organic solvents widely exist in the workplace and the environment around. PD may closely relate to the exposure to various solvents, especially TCE (Trichloroethylene, TCE). TCE is a common-used industrial solvent and the precursors of chloral hydrate, which widely exists in environment. Studies show that longterm exposure to TCE may induce clinical symptoms of PD, and animal experiment reveals that the loss of dopaminergic neurons in substantia nigra may be caused by the mechanism meditated by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline, TaClo), metabolite of TCE. Striatum stereotactic injection is a PD modeling method appeared in recent years. By striatum injection, the drug can be transported to substantia nigra through axonal transport, which would leads to pathological changes. Regarding whether Taclo striatum injection could result in PD behavioral changes, it has not been reported by far. Whether inflammatory response play a role in this process remains an open question. The literature of the application of striatum stereotactic injection to study the neurotoxic effect of dopaminergic neurons is very few both in China and overall the world. There has been no animal experiment on TaClo carried out in China by far. Through the implication of TaClo striatum stereotactic injection to rats, the problem about the relationship between the neurotoxic effect of dopaminergic neurons and cox-2expression is put forward.Objective To study Wistar rats’neurobehavioral changes and cox-2expression in substantia nigra after TaClo striatum stereotactic injection.Methods Stereotactic injection technology was adopted to inject TaClo dissolved in PEG (4μl,2.5μg/μl) to4sites of rats’striatum. PEG was injected to the rats of control group. At the7th,14th,21st and28th days after injection, the mean amount of drinking water of two groups was measured. Video analysis system for inner open field test was applied. The total time, distance and tracks involved in the rats’activity of two groups were recorded and compared. All the rats were executed, their brains taken out for cox-2histochemical staining.Results PD behaviors began to appear gradually among the TaClo striatum stereotactic injected rats in experimental group. The average amount of day water intake reduced. Average amount of day water intake in experimental group was less than that of the control (t=4.831, p=0.017). Average distance involved in the rats’ activity of the experimental group was obviously less than that of the control (t=14.317, p=0.000). Average time involved in the rats’activity of two groups showed no difference (t=1.151, p=0.268). Motion tracks showed that, with time going on, the rats’activities of experimental group became less, and the active region trended to reduce to the center area. Brown cox-2positive neurons (mainly microglias) appear in a large amount of endochylema located in the substantia nigra pars compacta of the rats in the experimemtal group. Cox-2reveals in the endochylema of neurons (maily microglias), and the outlines and nucleus of the positive staining neurons (mainly microglias) are clearly visible; few brown cox-2positive neurons (mainly microglias) appears in substantia nigra pars compacta of the rats in the control group, and the number of cox-2positive neurons in the control group is significantly less than that of the experimental group (P<0.05). In addition, the number of cox-2negative neurons (mainly dopaminergic neurons and astrocytes) in the substantia nigra pars compacta of the experimental group is significant less than that of the control group (P<0.05).Conclusion Taclo, one metabolite of environmental neurotoxin TCE, could lead to neurobehavioral changes of PD. Its mechanism is to cause inflammatory reaction by cox-2mediated substantia nigra, which induces PD.