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The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation.
Eur J Neurosci. 2005 Jul; 22(2):317-30.EJ

Abstract

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 p47phox 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.

Authors+Show Affiliations

Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London, SE1 1UL, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16045485

Citation

Iravani, Mahmoud M., et al. "The Acute and the Long-term Effects of Nigral Lipopolysaccharide Administration On Dopaminergic Dysfunction and Glial Cell Activation." The European Journal of Neuroscience, vol. 22, no. 2, 2005, pp. 317-30.
Iravani MM, Leung CC, Sadeghian M, et al. The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation. Eur J Neurosci. 2005;22(2):317-30.
Iravani, M. M., Leung, C. C., Sadeghian, M., Haddon, C. O., Rose, S., & Jenner, P. (2005). The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation. The European Journal of Neuroscience, 22(2), 317-30.
Iravani MM, et al. The Acute and the Long-term Effects of Nigral Lipopolysaccharide Administration On Dopaminergic Dysfunction and Glial Cell Activation. Eur J Neurosci. 2005;22(2):317-30. PubMed PMID: 16045485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation. AU - Iravani,Mahmoud M, AU - Leung,Clement C M, AU - Sadeghian,Mona, AU - Haddon,Claire O, AU - Rose,Sarah, AU - Jenner,Peter, PY - 2005/7/28/pubmed PY - 2005/9/24/medline PY - 2005/7/28/entrez SP - 317 EP - 30 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 22 IS - 2 N2 - 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 p47phox 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. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16045485/The_acute_and_the_long_term_effects_of_nigral_lipopolysaccharide_administration_on_dopaminergic_dysfunction_and_glial_cell_activation_ L2 - https://doi.org/10.1111/j.1460-9568.2005.04220.x DB - PRIME DP - Unbound Medicine ER -