Study On Amino Neurotransmitters, GABAergic Neuron And GABA_A Receptor MRNA Of Rats With Parkinson's Disease

Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause that occurs in adults. PD is morphologically characterized by progressive degeneration and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Evidence indicates that cholinergic and dopaminergic systems work together to produce the coordinated function of the striatum. Loss of that cooperative activity by the decrease of dopamine (DA) secretion contributes to the dysfunction underlying Parkinson's disease. Although significant advances have been made in understanding the underlying pathophysiology of this condition, the cause is still unknown.The increasing experimental data indicates anatomically and pathophysiologily that GABAergic system, Glutaminergic system and Dopaminergic system have many affinities in basal ganglia. It has been demonstrated the excitotoxicity caused by increase of glutamic acid leads to progressive degeneration and loss of dopaminergic neurons. Therefor, to investigate changes of content of GABA, GABAergic neuron and and GABAA receptor mRNA of subareas of basal ganglia in unilateral rat model of Parkinson's disease is very significant in theory and practice.The rat model of Parkinson's disease was made by right unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA) in this study. Thawed samples in substantia nigra pars reticulars (SNr), caudoputamen (CPu) and subthalamic nucleus (STN) were analyzed for amino neurohumor contents using established high performance liquid chromatography (HPLC) -electrochemicaldetection methods. GABAergic neurons were observed in morphological feature and quantitatively analyzed respectively by immunohistochemical (IHC) method and image analysis technigue in subareas of basal ganglia. The subunits a1, a 2, B 2 and r 2 of GABAA receptor in SNr, CPu and STN wre examined with Northern Enzyme linked immunosorbent assay (ELISA). The results show:1. The levels of glutamic acid (Glu) , aspartic acid (Asp) , glycine (Gly) and gamma-amino-butyric acid in lesion side were statistically significant increased (PO.01) . Theoretically, the increase of Glu content may augment the content of GABA. As a result, the increase of GABA reduce the content of Glu. Both levels of Glu and GABA will decrease under the interaction between themselves. However, this phenomenon was not observed.2. There were quite a few medium-sized and elliptic GABAergic positive neurons and a few multiangle neurons can be observed in SNr and STN in Vehicle group. There were abundant of small-sized and equably-distributed GABAergic positive neurons can be observed in CPu in Vehicle group. These GABAergic positive neurons in CPu are round or elliptic in shape, whose karyons are relatively large and whose cytoplasm are relatively small. The results demonstrated that GABAergic positive neurons in subareas of basal ganglia with 6-OHDA lesion were decreased in number significantly as compared with those in tham group (P<0.05). While GABAergic positive neurons in subareas of basal ganglia with Ketamine treat have no significantly change.3. In SNr of right unilateral 6-OHDA lesion rat, there was significant decrease of mRNA expression either in the subunit a , (P<0.01) of GABAA receptor or in the subunit a 2 (P<0.05) of GABAA receptor, and there were no significant changes in the subunits B 2 and r2 (P>0.05) of GABAA receptor. In CPu of right unilateral 6-OHDA lesion rat, there was significant decrease of mRNA expression both in the subunit a 1 (P<0.01) of GABAA receptor and in the subunit a 2 (P<0.01) of GABA A receptor, and there were no significant change in the subunits B 2 and r 2 (P >0.05) of GABAA receptor. In STN of right unilateral 6-OHDA lesion rat, there was significant decrease of mRNA expression both in the subunit a , (P<0.01) of GABAA receptor and in the subunit r 2(P<0.0l) of GABAA receptor, and there were no significant change in the subunits a 2 and B 2 (P>0.05) of GABAA receptor.4. Taken together, this study indicate that on account of decrease in n...