Protective effects of taurine on neurons and microglia in Parkinson's disease-like mouse model induced by paraquat

Abstract

Objective: To investigate the protective effect of taurine (Tau) on hippocampus, substantia nigra neurons and microglia in paraquat (PQ) -induced Pakinson's disease-like mice. Methods: In April 2019, the specific pathogen free (SPF) C57BL/6 mice (n=36) were randomly divided into control group (NaCl) , Tau control group (150 mg/kg) , PQ exposure group (10 mg/kg PQ group, 15 mg/kg PQ group) , Tau intervention group (Tau+10 mg/kg PQ group, Tau+15 mg/kg PQ group) , respectively. Tau was used in 1 h before PQ administration for consecutive 6 weeks (twice per week) . General and neurobehavioral tests (Traction test, Open field test, Forced Swimming test, Tail suspension test, High plus maze and Object recognition test) were performed to test motor and cognitive function. After neuroethology detection, mice were euthanized and brains were collected. Nissl staining was used to detect the changes of the number and morphology of Nissl bodies in hippocampus and substantia nigra neurons of mice. Immunohistochemistry (IHC) was used to test the levels of neuron marker neuronal nuclei antigen (NeuN) , substantia nigra dopaminergic neuron marker tyrosine hydroxylase (TH) , α-synuclein (α-syn) , microglia markers ionized calcium bindingadaptor molecule-1 (Iba-1) , inducible nitric oxide synthase (iNOS) and interleukin-1β (IL-1β) in mice substantia nigra. The coexpression of Iba-1 and TH double-labeling, α-syn and TH double-labeling in mice substantia nigra were measured by immunofluorescence double staining. Results: General behavioral changes such as slow reaction and reduced action occurred in mice of PQ group. Compared with the control group, the scores of Traction test, and the time ratio of new object recognition in the PQ group decreased (P<0.05) , the fixed time of Swimming test and Tail suspension test increased (P<0.05) , the horizontal crawl number and vertical times of Open field test and the ratio of open arm residence time of High plus maze in the 15 mg/kg PQ group decreased (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed increased scores in Traction test (P<0.05) and decreased fixed time of Swimming test and Tail suspension test (P<0.05) . Compared with the 15 mg/kg PQ group, the horizontal crawl number of Open field test and the time ratio of new object recognition increased in the Tau+15 mg/kg PQ group (P<0.05) . Compared with the control group, the PQ group showed a decrease in the number of Nissl body in the hippocampus and substantia nigra (P<0.05) , a decrease in the number of NeuN and TH positive cells in the substantia nigra (P<0.05) , with a large number of α-syn deposition, Iba-1 activation of microglia cells, and an increase in the expression of inflammatory factors (IL-1β, iNOS) in the hippocampus and substantia nigra (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed the number of Nissl in the hippocampus and substantia nigra was significantly increased (P<0.05) , the number of NeuN and TH positive cells in the substantia nigra was significantly increased (P<0.05) , the expression levels of α-syn, Iba-1 and inflammatory factors (IL-1β, iNOS) in the substantia nigra were significantly decreased (P<0.05) . Conclusion: Tau could protect PQ-induced degeneration of substantia nigra dopaminergic neurons and hippocampal neuron loss by inhibiting the activation of microglia cells and release of inflammatory factors, and effectively improve the neurobehavioral and brain histopathological changes of PQ-induced PD-like mice.