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Activated microglia affect the nigro-striatal dopamine neurons differently in neonatal and aged mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
J Neurosci Res. 2007 Jun; 85(8):1752-61.JN

Abstract

Microglia play an important role in the inflammatory process that occurs in Parkinson's disease (PD). Activated microglia produce cytokines and neurotrophins and may have neurotoxic or neurotrophic effects. Because microglia are most proliferative and easily activated during the neonatal period, we examined the effects of neonatal microglia activated with lipopolysaccharide (LPS) on the nigro-striatal dopamine neurons in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in comparison with activated microglia from the aged mice. By MPTP administration to neonatal mice, the number of dopamine neurons in the substantia nigra (SN) was decreased significantly, whereas that in the mice treated with LPS and MPTP was recovered to normal, along with significant microglial activation. Tyrosine hydroxylase (TH) activity, the levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), and the levels of pro-inflammatory cytokines IL-1beta and IL-6 in the midbrain were elevated in the neonates treated with LPS and MPTP. On the contrary, although the number of dopamine neurons in the 60-week-old mice treated with MPTP was also decreased significantly, the microglial activation by LPS treatment caused a further decrease in their number. These results suggest that the activated microglia in neonatal mice are different from those in aged mice, with the former having neurotrophic potential toward the dopamine neurons in the SN, in contrast to the neurotoxic effect of the latter.

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Authors+Show Affiliations

Sawada H
School of Medicine, Fujita Health University, Toyoake, Japan.
Hishida R
No affiliation info available
Hirata Y
No affiliation info available
Ono K
No affiliation info available
Suzuki H
No affiliation info available
Muramatsu S
No affiliation info available
Nakano I
No affiliation info available
Nagatsu T
No affiliation info available
Sawada M
No affiliation info available

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine3,4-Dihydroxyphenylacetic AcidAgingAnimalsAnimals, NewbornCell CountCorpus StriatumCytokinesDopamineLipopolysaccharidesMaleMiceMice, Inbred C57BLMicrogliaNerve DegenerationNerve Growth FactorsNeuronsParkinsonian DisordersSubstantia NigraTyrosine 3-Monooxygenase

Pub Type(s)

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

Language

eng

PubMed ID

17469135

Citation

Sawada, Hirohide, et al. "Activated Microglia Affect the Nigro-striatal Dopamine Neurons Differently in Neonatal and Aged Mice Treated With 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine." Journal of Neuroscience Research, vol. 85, no. 8, 2007, pp. 1752-61.
Sawada H, Hishida R, Hirata Y, et al. Activated microglia affect the nigro-striatal dopamine neurons differently in neonatal and aged mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurosci Res. 2007;85(8):1752-61.
Sawada, H., Hishida, R., Hirata, Y., Ono, K., Suzuki, H., Muramatsu, S., Nakano, I., Nagatsu, T., & Sawada, M. (2007). Activated microglia affect the nigro-striatal dopamine neurons differently in neonatal and aged mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Journal of Neuroscience Research, 85(8), 1752-61.
Sawada H, et al. Activated Microglia Affect the Nigro-striatal Dopamine Neurons Differently in Neonatal and Aged Mice Treated With 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurosci Res. 2007;85(8):1752-61. PubMed PMID: 17469135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activated microglia affect the nigro-striatal dopamine neurons differently in neonatal and aged mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. AU - Sawada,Hirohide, AU - Hishida,Ryohei, AU - Hirata,Yoko, AU - Ono,Kenji, AU - Suzuki,Hiromi, AU - Muramatsu,Shin-ichi, AU - Nakano,Imaharu, AU - Nagatsu,Toshiharu, AU - Sawada,Makoto, PY - 2007/5/1/pubmed PY - 2007/11/6/medline PY - 2007/5/1/entrez SP - 1752 EP - 61 JF - Journal of neuroscience research JO - J Neurosci Res VL - 85 IS - 8 N2 - Microglia play an important role in the inflammatory process that occurs in Parkinson's disease (PD). Activated microglia produce cytokines and neurotrophins and may have neurotoxic or neurotrophic effects. Because microglia are most proliferative and easily activated during the neonatal period, we examined the effects of neonatal microglia activated with lipopolysaccharide (LPS) on the nigro-striatal dopamine neurons in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in comparison with activated microglia from the aged mice. By MPTP administration to neonatal mice, the number of dopamine neurons in the substantia nigra (SN) was decreased significantly, whereas that in the mice treated with LPS and MPTP was recovered to normal, along with significant microglial activation. Tyrosine hydroxylase (TH) activity, the levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), and the levels of pro-inflammatory cytokines IL-1beta and IL-6 in the midbrain were elevated in the neonates treated with LPS and MPTP. On the contrary, although the number of dopamine neurons in the 60-week-old mice treated with MPTP was also decreased significantly, the microglial activation by LPS treatment caused a further decrease in their number. These results suggest that the activated microglia in neonatal mice are different from those in aged mice, with the former having neurotrophic potential toward the dopamine neurons in the SN, in contrast to the neurotoxic effect of the latter. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/17469135/Activated_microglia_affect_the_nigro_striatal_dopamine_neurons_differently_in_neonatal_and_aged_mice_treated_with_1_methyl_4_phenyl_1236_tetrahydropyridine_ L2 - https://doi.org/10.1002/jnr.21241 DB - PRIME DP - Unbound Medicine ER -