4-Aminopyridine Improves Spatial Memory in a Murine Model of HIV-1 Encephalitis
| Autor: | Huangui Xiong, Howard E. Gendelman, James Keblesh, Huanyu Dou |
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| Rok vydání: | 2009 |
| Předmět: |
Male
AIDS Dementia Complex Long-Term Potentiation Immunology Central nervous system Neuroscience (miscellaneous) Hippocampus Cell Separation Mice SCID Water maze Monocytes Article Proinflammatory cytokine Mice Channelopathy Memory Potassium Channel Blockers medicine Animals Learning Immunology and Allergy 4-Aminopyridine Maze Learning Swimming Pharmacology Microglia Brain Long-term potentiation medicine.disease Microscopy Electron Electrophysiology medicine.anatomical_structure Potassium Channels Voltage-Gated Space Perception Synapses HIV-1 Psychology Neuroscience |
| Zdroj: | Journal of Neuroimmune Pharmacology. 4:317-327 |
| ISSN: | 1557-1904 1557-1890 |
| DOI: | 10.1007/s11481-009-9161-7 |
| Popis: | HIV-1-associated neurocognitive disorders (HAND) remains a significant source of morbidity in the era of wide spread use of highly active antiretroviral therapy. Disease is precipitated by low levels of viral growth and glial immune activation within the central nervous system. Blood borne macrophage and microglia affect a proinflammatory response and release viral proteins that affects neuronal viability and leads to death of nerve cells. Increasing evidence supports the notion that HAND is functional channelopathy, but proof of this concept remains incomplete. Based on their role in learning and memory processes, we now posit that voltage-gated potassium (K(v)) channels could be a functional substrate for disease. This was tested in the severe combined immunodeficient (SCID) mouse model of HIV-1 encephalitis (HIVE) by examining whether the K(v) channel blocker, 4-aminopyridine (4-AP), could affect behavioral, electrophysiological, and morphological measures of learning and memory. HIVE SCID mice showed impaired spatial memory in radial arm water maze tests. Electrophysiology studies revealed a reduction of long-term potentiation (LTP) in the CA1 region of the hippocampus. Importantly, systemic administration of 4-AP blocked HIV-1-associated reduction of LTP and improved animal performance in the radial arm water maze. These results support the importance of K(v) channel dysfunction in disease but, more importantly, provide a potential target for adjunctive therapies for HAND. |
| Databáze: | OpenAIRE |
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