Tags

Type your tag names separated by a space and hit enter

Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia.
Brain Res Mol Brain Res. 2005 Mar 24; 134(1):162-9.BR

Abstract

Parkinson's disease is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Accumulating evidence supports the notion that neuroinflammation is involved in the pathogenesis of this disease. Valproate (VPA) has long been used for the treatment of seizures and bipolar mood disorder. In vivo and in vitro studies have demonstrated that VPA has neuroprotective and neurotrophic actions. In this study, using primary neuron-glia cultures from rat midbrain, we demonstrated that VPA is a potent neuroprotective agent against lipopolysaccharide (LPS)-induced neurotoxicity. Results showed that pretreatment with 0.6 mM VPA for 48 h robustly attenuated LPS-induced degeneration of dopaminergic neurons as determined by [(3)H] dopamine uptake and counting of the number of TH-ir neurons. The neuroprotective effect of VPA was concentration-dependent and was mediated, at least in part, through a decrease in levels of pro-inflammatory factors released from activated microglia. Specifically, LPS-induced increase in the release of TNFa, NO, and intracellular reactive oxygen species was markedly reduced in cultures pretreated with VPA. These anti-inflammatory effects of VPA were time and concentration-dependent correlated with a decrease in the number of microglia. Thus, our results demonstrate that protracted VPA pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity through a reduction in levels of released pro-inflammatory factors, and further suggest that these anti-inflammatory effects may be contributed by VPA-induced reduction of microglia cell number. Taken together, our study reinforces the view that VPA may have utility in treating Parkinson's disease.

Authors+Show Affiliations

Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15790540

Citation

Peng, Giia-Sheun, et al. "Valproate Pretreatment Protects Dopaminergic Neurons From LPS-induced Neurotoxicity in Rat Primary Midbrain Cultures: Role of Microglia." Brain Research. Molecular Brain Research, vol. 134, no. 1, 2005, pp. 162-9.
Peng GS, Li G, Tzeng NS, et al. Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia. Brain Res Mol Brain Res. 2005;134(1):162-9.
Peng, G. S., Li, G., Tzeng, N. S., Chen, P. S., Chuang, D. M., Hsu, Y. D., Yang, S., & Hong, J. S. (2005). Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia. Brain Research. Molecular Brain Research, 134(1), 162-9.
Peng GS, et al. Valproate Pretreatment Protects Dopaminergic Neurons From LPS-induced Neurotoxicity in Rat Primary Midbrain Cultures: Role of Microglia. Brain Res Mol Brain Res. 2005 Mar 24;134(1):162-9. PubMed PMID: 15790540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia. AU - Peng,Giia-Sheun, AU - Li,Guorong, AU - Tzeng,Nian-Sheng, AU - Chen,Po-See, AU - Chuang,De-Maw, AU - Hsu,Yaw-Don, AU - Yang,Sufen, AU - Hong,Jau-Shyong, Y1 - 2004/11/25/ PY - 2004/09/06/received PY - 2004/09/06/revised PY - 2004/10/08/accepted PY - 2005/3/26/pubmed PY - 2005/6/14/medline PY - 2005/3/26/entrez SP - 162 EP - 9 JF - Brain research. Molecular brain research JO - Brain Res Mol Brain Res VL - 134 IS - 1 N2 - Parkinson's disease is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Accumulating evidence supports the notion that neuroinflammation is involved in the pathogenesis of this disease. Valproate (VPA) has long been used for the treatment of seizures and bipolar mood disorder. In vivo and in vitro studies have demonstrated that VPA has neuroprotective and neurotrophic actions. In this study, using primary neuron-glia cultures from rat midbrain, we demonstrated that VPA is a potent neuroprotective agent against lipopolysaccharide (LPS)-induced neurotoxicity. Results showed that pretreatment with 0.6 mM VPA for 48 h robustly attenuated LPS-induced degeneration of dopaminergic neurons as determined by [(3)H] dopamine uptake and counting of the number of TH-ir neurons. The neuroprotective effect of VPA was concentration-dependent and was mediated, at least in part, through a decrease in levels of pro-inflammatory factors released from activated microglia. Specifically, LPS-induced increase in the release of TNFa, NO, and intracellular reactive oxygen species was markedly reduced in cultures pretreated with VPA. These anti-inflammatory effects of VPA were time and concentration-dependent correlated with a decrease in the number of microglia. Thus, our results demonstrate that protracted VPA pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity through a reduction in levels of released pro-inflammatory factors, and further suggest that these anti-inflammatory effects may be contributed by VPA-induced reduction of microglia cell number. Taken together, our study reinforces the view that VPA may have utility in treating Parkinson's disease. SN - 0169-328X UR - https://www.unboundmedicine.com/medline/citation/15790540/Valproate_pretreatment_protects_dopaminergic_neurons_from_LPS_induced_neurotoxicity_in_rat_primary_midbrain_cultures:_role_of_microglia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-328X(04)00480-2 DB - PRIME DP - Unbound Medicine ER -