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Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease.
Mol Psychiatry. 2004 Apr; 9(4):371-85.MP

Abstract

We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA injection, lithium significantly diminished the loss of neurons immunostained for Neuronal Nuclei (NeuN) in the injured striatum, but failed to prevent the reduction of NADPH-diaphorase-positive striatal interneurons. Lithium also reduced the number of neurons showing DNA damage or activated caspase-3. This neuroprotection was associated with an upregulation of Bcl-2 protein levels in the striatal tissue and an increase in the number and density of Bcl-2 immunostaining in striatal neurons. Bromodeoxyuridinie (BrdU) labeling in the lithium-treated injured striatum revealed the presence of large numbers of proliferating cells near the QA-injection site, with a reduction of BrdU-labeled cells in the subventricular zone (SVZ). All BrdU-labeled cells in the SVZ and the majority of BrdU-labeled cells near the QA-injection site were negative for either NeuN or glial fibrillary acidic protein (GFAP), suggesting that they are undifferentiated progenitor cells. However, a small number of BrdU-positive cells found in the QA-injected and lithium-treated striatum site were positive for either NeuN or GFAP. Our results suggest that lithium is neuroprotective in the QA-injection model of Huntington's disease not only due to its ability to inhibit apoptosis but also because it can stimulate neuronal and astroglial progenitor proliferation in the QA-injected striatum or their migration from the SVZ.

Authors+Show Affiliations

Senatorov VV
Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. chuang@mail.nih.gov
Ren M
No affiliation info available
Kanai H
No affiliation info available
Wei H
No affiliation info available
Chuang DM
No affiliation info available

MeSH

AnimalsApoptosisCell DivisionCell SurvivalCorpus StriatumDNA DamageDose-Response Relationship, DrugHuntington DiseaseInterneuronsLithiumMaleNeuronsNeuroprotective AgentsNeurotoxinsProto-Oncogene Proteins c-bcl-2Quinolinic AcidRatsRats, Sprague-DawleyUp-Regulation

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

14702090

Citation

Senatorov, V V., et al. "Short-term Lithium Treatment Promotes Neuronal Survival and Proliferation in Rat Striatum Infused With Quinolinic Acid, an Excitotoxic Model of Huntington's Disease." Molecular Psychiatry, vol. 9, no. 4, 2004, pp. 371-85.
Senatorov VV, Ren M, Kanai H, et al. Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease. Mol Psychiatry. 2004;9(4):371-85.
Senatorov, V. V., Ren, M., Kanai, H., Wei, H., & Chuang, D. M. (2004). Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease. Molecular Psychiatry, 9(4), 371-85.
Senatorov VV, et al. Short-term Lithium Treatment Promotes Neuronal Survival and Proliferation in Rat Striatum Infused With Quinolinic Acid, an Excitotoxic Model of Huntington's Disease. Mol Psychiatry. 2004;9(4):371-85. PubMed PMID: 14702090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease. AU - Senatorov,V V, AU - Ren,M, AU - Kanai,H, AU - Wei,H, AU - Chuang,D-M, PY - 2004/1/1/pubmed PY - 2004/12/23/medline PY - 2004/1/1/entrez SP - 371 EP - 85 JF - Molecular psychiatry JO - Mol Psychiatry VL - 9 IS - 4 N2 - We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA injection, lithium significantly diminished the loss of neurons immunostained for Neuronal Nuclei (NeuN) in the injured striatum, but failed to prevent the reduction of NADPH-diaphorase-positive striatal interneurons. Lithium also reduced the number of neurons showing DNA damage or activated caspase-3. This neuroprotection was associated with an upregulation of Bcl-2 protein levels in the striatal tissue and an increase in the number and density of Bcl-2 immunostaining in striatal neurons. Bromodeoxyuridinie (BrdU) labeling in the lithium-treated injured striatum revealed the presence of large numbers of proliferating cells near the QA-injection site, with a reduction of BrdU-labeled cells in the subventricular zone (SVZ). All BrdU-labeled cells in the SVZ and the majority of BrdU-labeled cells near the QA-injection site were negative for either NeuN or glial fibrillary acidic protein (GFAP), suggesting that they are undifferentiated progenitor cells. However, a small number of BrdU-positive cells found in the QA-injected and lithium-treated striatum site were positive for either NeuN or GFAP. Our results suggest that lithium is neuroprotective in the QA-injection model of Huntington's disease not only due to its ability to inhibit apoptosis but also because it can stimulate neuronal and astroglial progenitor proliferation in the QA-injected striatum or their migration from the SVZ. SN - 1359-4184 UR - https://www.unboundmedicine.com/medline/citation/14702090/Short_term_lithium_treatment_promotes_neuronal_survival_and_proliferation_in_rat_striatum_infused_with_quinolinic_acid_an_excitotoxic_model_of_Huntington's_disease_ DB - PRIME DP - Unbound Medicine ER -