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The acute and the long‐term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation
Author(s) -
Iravani Mahmoud M.,
Leung Clement C. M.,
Sadeghian Mona,
Haddon Claire O.,
Rose Sarah,
Jenner Peter
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04220.x
Subject(s) - substantia nigra , glial fibrillary acidic protein , microglia , astrocyte , tyrosine hydroxylase , dopaminergic , endocrinology , medicine , pars compacta , nitric oxide synthase , neuroglia , mptp , chemistry , nitric oxide , dopamine , biology , inflammation , central nervous system , immunohistochemistry
Sustained reactive microgliosis may contribute to the progressive degeneration of nigral dopaminergic neurons in Parkinson's disease (PD), in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) exposed human and in non‐human primates. However, the temporal relationship between glial cell activation and nigral cell death is relatively unexplored. Consequently, the effects of acute (24 h) and chronic (30 days) glial cell activation induced by unilateral supranigral lipopolysaccharide (LPS) administration were studied in rats. At 24 h, LPS administration caused a marked reduction in the number of tyrosine hydroxylase‐immunoreactive (TH‐ir) neurons in the substantia nigra (SN) but striatal TH‐ir was unaffected. By 30 days, the loss of TH‐positive neurons in the LPS‐treated nigra was no greater than at 24 h although a heterogeneous loss of striatal TH‐ir was present. The loss of nigrostriatal neurons was of functional significance, as at 30 days, LPS‐treated rats exhibited ipsiversive circling in response to (+)‐amphetamine administration. At 24 h, there was a moderate increase in glial fibrillary acidic protein (GFAP)‐ir astrocytes in the SN but a marked elevation of p47 phox positive OX‐42‐ir microglia, and intense inducible nitric oxide synthase (iNOS)‐ir and 3‐nitrotyrosine (3‐NT)‐ir was present. However, by 30 days the morphology of OX‐42‐ir microglia returned to a resting state, the numbers were greatly reduced and no 3‐NT‐ir was present. At 30 days, GFAP‐ir astrocytes were markedly increased in number and iNOS‐ir was present in fibrillar astrocyte‐like cells. This study shows that acute glial activation leading to dopaminergic neuron degeneration is an acute short‐lasting response that does not itself perpetuate cell death or lead to prolonged microglial activation.