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Decreased sensitivity to MPTP in NFL−/− transgenic mice
Author(s) -
Chao Yinxia,
He Beiping,
Tay Samuel SW
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a879-a
Subject(s) - mptp , sensitivity (control systems) , transgene , genetically modified mouse , chemistry , medicine , biochemistry , engineering , dopamine , gene , dopaminergic , electronic engineering
Besides environmental factors, many genetic factors have been confirmed to contribute to the pathogenesis of Parkinson's disease (PD). Previous studies have shown that protein aggregation will be formed inside neurons after the depletion of neurofilament light peptide (NFL). In this study, we investigated the possible interaction between the NFL gene and neurotoxins by testing whether the mice with NFL deficiency would show different sensitivity to secondary toxic exposure such as 1 methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP). In NFL−/− mice without MPTP treatment, no obvious loss of nigrostriatal tyrosine hydroxylase (TH)‐positive neurons was observed compared to the normal control. However, a downregulation of complement receptor type 3 expression in microglia was noted in NFL−/− mice. After acute treatment with MPTP (80mg/kg body weight), a decrease in the deterioration of the nigrostriatal dopaminergic neurons assessed by quantitation of nigrostriatal TH‐positive neurons in NFL−/− mice was observed compared to non‐transgenic C57BL6/J controls, while a more intense astrocytic activation was seen in the NFL−/− mice. The present results demonstrate that the NFL gene deletion may lead to a neuroprotective effect in MPTP intoxicated animals.