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Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally.
Exp Neurol. 2006 Jun; 199(2):499-512.EN

Abstract

Toxin-induced animal models of Parkinson's disease (PD) exhibit many of the same neuroinflammatory changes seen in patients suggesting a role for inflammation in DA neuron loss. Yet, despite this inflammation, the progressive loss of DA neurons that characterizes PD is rarely seen in animals. We infused lipopolysaccharide (LPS) or saline into 7-month-old rats that had been exposed to LPS or saline prenatally and assessed them for DA neuron loss and inflammatory measures (interleukin 1 beta, tumor necrosis factor-alpha, glutathione, and activated microglia) over a period of 84 days to examine the role of pre-existing inflammation in progressive DA neuron loss. LPS infusion into both prenatal treatment groups produced neuroinflammation during the 14 days of LPS infusion that subsequently reverted toward normal over the next 70 days. In animals with pre-existing inflammation (i.e., prenatal LPS), however, the acute changes seen were attenuated, but took much longer to return to normal suggesting a prolonged inflammatory response. These inflammatory changes were consistent with the greater acute DA neuron loss seen in the prenatal saline controls and the progressive DA neuron loss seen only in the animals exposed to LPS prenatally. Interestingly, both prenatal treatment groups exhibited increases in microglia over the entire 84-day course of the study. These data suggest that pre-existing neuroinflammation prolongs the inflammatory response that occurs with a second toxic exposure, which may be responsible for progressive DA neuron loss. This provides further support for the "multiple hit" hypothesis of PD.

Authors+Show Affiliations

Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA.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, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16504177

Citation

Ling, Zaodung, et al. "Progressive Dopamine Neuron Loss Following Supra-nigral Lipopolysaccharide (LPS) Infusion Into Rats Exposed to LPS Prenatally." Experimental Neurology, vol. 199, no. 2, 2006, pp. 499-512.
Ling Z, Zhu Y, Tong Cw, et al. Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally. Exp Neurol. 2006;199(2):499-512.
Ling, Z., Zhu, Y., Tong, C. w., Snyder, J. A., Lipton, J. W., & Carvey, P. M. (2006). Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally. Experimental Neurology, 199(2), 499-512.
Ling Z, et al. Progressive Dopamine Neuron Loss Following Supra-nigral Lipopolysaccharide (LPS) Infusion Into Rats Exposed to LPS Prenatally. Exp Neurol. 2006;199(2):499-512. PubMed PMID: 16504177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally. AU - Ling,Zaodung, AU - Zhu,Yuangui, AU - Tong,Chong wai, AU - Snyder,Joshua A, AU - Lipton,Jack W, AU - Carvey,Paul M, Y1 - 2006/02/28/ PY - 2005/10/21/received PY - 2005/12/08/revised PY - 2006/01/12/accepted PY - 2006/3/1/pubmed PY - 2006/8/12/medline PY - 2006/3/1/entrez SP - 499 EP - 512 JF - Experimental neurology JO - Exp Neurol VL - 199 IS - 2 N2 - Toxin-induced animal models of Parkinson's disease (PD) exhibit many of the same neuroinflammatory changes seen in patients suggesting a role for inflammation in DA neuron loss. Yet, despite this inflammation, the progressive loss of DA neurons that characterizes PD is rarely seen in animals. We infused lipopolysaccharide (LPS) or saline into 7-month-old rats that had been exposed to LPS or saline prenatally and assessed them for DA neuron loss and inflammatory measures (interleukin 1 beta, tumor necrosis factor-alpha, glutathione, and activated microglia) over a period of 84 days to examine the role of pre-existing inflammation in progressive DA neuron loss. LPS infusion into both prenatal treatment groups produced neuroinflammation during the 14 days of LPS infusion that subsequently reverted toward normal over the next 70 days. In animals with pre-existing inflammation (i.e., prenatal LPS), however, the acute changes seen were attenuated, but took much longer to return to normal suggesting a prolonged inflammatory response. These inflammatory changes were consistent with the greater acute DA neuron loss seen in the prenatal saline controls and the progressive DA neuron loss seen only in the animals exposed to LPS prenatally. Interestingly, both prenatal treatment groups exhibited increases in microglia over the entire 84-day course of the study. These data suggest that pre-existing neuroinflammation prolongs the inflammatory response that occurs with a second toxic exposure, which may be responsible for progressive DA neuron loss. This provides further support for the "multiple hit" hypothesis of PD. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/16504177/Progressive_dopamine_neuron_loss_following_supra_nigral_lipopolysaccharide__LPS__infusion_into_rats_exposed_to_LPS_prenatally_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(06)00018-5 DB - PRIME DP - Unbound Medicine ER -