QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 14, 2005, 25(37):8375-8385; doi:10.1523/JNEUROSCI.2164-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Dou, H. Articles by Gendelman, H. E. Search for Related Content PubMed PubMed Citation Articles by Dou, H. Articles by Gendelman, H. E.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Neuroprotective Mechanisms of Lithium in Murine Human Immunodeficiency Virus-1 Encephalitis

Huanyu Dou,^1,2 Brent Ellison,¹ Jennifer Bradley,^1,2 Alexander Kasiyanov,^1,2 Larisa Y. Poluektova,^1,2 Huangui Xiong,^1,2 Sanjay Maggirwar,⁴ Stephen Dewhurst,⁴ Harris A. Gelbard,⁴ and Howard E. Gendelman^1,2,3

¹Center for Neurovirology and Neurodegenerative Disorders, ²Departments of Pharmacology and Experimental Neuroscience, and ³Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, and ⁴The Center for Aging and Developmental Biology, Departments of Neurology, Pediatrics, and Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642

Lithium (Li) has garnered considerable interest as a neuroprotective drug for a broad range of nervous system disorders. Its neuroprotective activities occur as a consequence of glycogen synthase kinase-3 (GSK-3) inhibition leading to downstream blockade of -catenin and Tau phosphorylation. In the present study, we investigated Li-mediated neuroprotective mechanisms in laboratory and murine human immunodeficiency virus-1 (HIV-1) encephalitis (HIVE) models. In laboratory tests, Li protected neurons from neurotoxic secretions of HIV-1-infected monocyte-derived macrophages (MDMs). This neuroprotection was mediated, in part, through the phosphatidyl inositol 3-kinase/Akt and GSK-3 pathways. To examine the effects of Li treatment in vivo, MDMs were injected into the basal ganglia of severe combined immunodeficient mice and then Li was administered (60 mg/kg/d). Seven days after MDM injection, mice were killed and CNS tissue was collected and subjected to immunocytochemical and Western blot assays for leukocyte and neural antigens, GSK-3, and key kinase substrates such as-catenin and Tau. Numbers of HIV-1 p24 antigen-positive MDMs were unaltered by Li treatment of HIVE mice. Similarly, the greatly increased extent of astrocyte and microglia activation in HIVE mice (10-fold and 16-fold, respectively, compared with unmanipulated controls) was also unaltered by Li. In contrast, Li restored HIVE-associated loss of microtubule-associated protein-2-positive neurites and synaptic density while reducing levels or activity of phospho-Tau Ser²⁰², phospho--catenin, and GSK-3. Electrophysiological recordings showed diminished long-term potentiation in hippocampal slices of HIVE mice that were restored by Li. Based on these data, the use of Li as an adjuvant for HIV-1-associated dementia is now being pursued.

Key words: HIV-1 encephalitis; lithium; neuroprotection; monocyte-derived macrophages; glycogen synthase kinase-3; neurodegeneration

---

Received Jan 8, 2005; revised June 24, 2005; accepted July 25, 2005.

This article has been cited by other articles:

				E. M. Yazlovitskaya, E. Edwards, D. Thotala, A. Fu, K. L. Osusky, W. O. Whetsell Jr., B. Boone, E. T. Shinohara, and D. E. Hallahan Lithium Treatment Prevents Neurocognitive Deficit Resulting from Cranial Irradiation Cancer Res., December 1, 2006; 66(23): 11179 - 11186. [Abstract] [Full Text] [PDF]

				A. Capetti, S. Landonio, I. Faggion, and G. Rizzardini Drop in Plasma Lithium Levels in 2 Patients on Concomitant Boosted Protease Inhibitor Regimens J Int Assoc Physicians AIDS Care (Chic Ill), September 1, 2006; 5(3): 119 - 120. [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help