Neuroprotective activities of sodium valproate in a murine model of human immunodeficiency virus-1 encephalitis
| Autor: | Santhi Gorantla, Stephen Dewhurst, Howard E. Gendelman, Harris A. Gelbard, Larisa Y. Poluektova, Jill Faraci, Huanyu Dou, Sanjay B. Maggirwar, Kevin Birusingh |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
AIDS Dementia Complex Neurite medicine.medical_treatment HIV Core Protein p24 tau Proteins Mice SCID Pharmacology Biology HIV Envelope Protein gp120 Neuroprotection Basal Ganglia Monocytes Rats Sprague-Dawley Mice GSK-3 medicine Animals Humans Nuclear protein Phosphorylation Cells Cultured Neurons General Neuroscience Macrophages Valproic Acid Neurodegeneration Neurotoxicity Cell Differentiation medicine.disease Coculture Techniques Rats Disease Models Animal Anticonvulsant Neuroprotective Agents Immunology biology.protein HIV-1 RNA Viral NeuN Neuroglia Biomarkers Cellular/Molecular |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 23(27) |
| ISSN: | 1529-2401 |
| Popis: | Human immunodeficiency virus-1 (HIV-1) infection of the nervous system can result in neuroinflammatory events leading first to neuronal dysfunction then to cognitive and behavioral impairments in infected people. The multifaceted nature of the disease process, commonly called HIV-1-associated dementia (HAD), provides a number of adjunctive therapeutic opportunities. One proposed adjunctive therapy is sodium valproate (VPA), an anticonvulsant known to promote neurite outgrowth and increase β-catenin through inhibiting glycogen synthase kinase 3β activity and tau phosphorylation. We now show that VPA treatment of rat cortical neurons exposed to HIV-1 gp120 prevents resultant neurotoxic activities. This includes the induction of significant neurite outgrowth and microtubule-associated protein 2 (MAP-2) and neuron-specific nuclear protein (NeuN) antigens in affected neuronal cell bodies and processes. Similarly, VPA protects severe combined immunodeficient (SCID) mice against the neurodegeneration of HIV-1ADAinfected monocyte-derived macrophages (MDMs). In SCID mice with HIV-1 MDM-induced encephalitis, VPA treatment significantly reduced neuronal phosphorylatedβ-catenin and tau without affecting HIV-1 replication or glial activation. We conclude that VPA protects neurons against HIV-1 infected MDM neurotoxicity, possibly through its effects on the phosphorylation of tau and β-catenin. The use of VPA as an adjuvant in treatment of human HAD is being pursued. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|