Nicotine inhibits the infiltration of T lympbcytes produced by 6-hydroxydopamine lesion in the striatum of SD rat

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Author:
ZHOU Ming(Laboratory of Neurobiology, Beijing Institute of Geriatrics, Key Laboratory for Neurodegenerative Diseases of Education Ministry, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China)
XU Zheng-li(Laboratory of Neurobiology, Beijing Institute of Geriatrics, Key Laboratory for Neurodegenerative Diseases of Education Ministry, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China)
CHEN Biao(Laboratory of Neurobiology, Beijing Institute of Geriatrics, Key Laboratory for Neurodegenerative Diseases of Education Ministry, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China)
Journal Title:
CHINESE JOURNAL OF NEUROMEDICINE
Issue:
Volume 7, Issue 07, 2008
DOI:
Key Word:
Nicotine;Parkinson's disease;6-OHDA;T lymphocyte

Abstract: Objective To explore the mechanism through which nicotine protects dopaminergic neurons against 6-hydroxydopamine (6-OHDA) toxicity in Parkinson's disease (PD) rat model. Methods Sixty Female SD rats were divided into 3 groups according to randomly digital table: High dosage group (nicotine 2 mg/kg, 5 injections I.p. Per day at 2-h interval), low dosage group (nicotine 0.2 mg/kg, 5 injections I.p. Per day at 2-h interval) and model group (normal saline treatment), n=20 each group. On day 8 after the treatment, a single injection of 20 ug of 6-OHDA was administered into striatum. Nicotine or normal saline was administered continuously daily until animals were killed. The dopaminergic neurons and CD3, CD4 and CDS-positive lymphocytes were analyzed quantitatively using immunohistochemistry and stereology. Results Four weeks after 6-OHDA administration, in the normal saline treated group, tyrosine hydroxylase-immunopositive cells in the substantia nigra of administered side was 25.27% of those in the one of non-administered side, and the immunopositive cells in 0.2 and 2 mg/kg nicotine treated groups were respectively 64.97% and 67.24% of those in the non-administered side. The loss of dopaminergic neurons induced by 6-OHDA in the substantia nigra was significantly less severe in the nicotine treatment groups (at both 0.2 and 2 mg/kg groups) than the saline treated group. T lymphocyte infiltration was markedly induced by 6-OHDA administration into striatum in all groups. In the striatum, we observed that the numbers of CD3, CD4 and CD8-positive lymphocytes were reduced significantly in the nicotine treated animals as compared to saline controls (P<0.05). The proportions of CD4 and CD8 positive cells in the total T lymphocytes were roughly equivalent in all groups at all time points, and there were no significant difference between nicotine treated groups and saline treated group. Conclusion Nicotine may have a neuroprotective effect against 6-OHDA induced dopaminergic lesion by inhibiting the infiltration of T lymphocytes and inflammation.

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