Memantine protects hippocampal neuronal function in murine human immunodeficiency virus type 1 encephalitis

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Memantine, a low-to-moderate-affinity NMDA receptor antagonist, can be used to treat cognitive impairment associated with Alzheimer's disease. However, its potential neuroprotective effects for human immunodeficiency virus type 1-associated (HIV-1-associated) dementia are less well appreciated. To this end we studied hippocampal synaptic function in a severe combined immunodeficient (SCID) mouse model of HIV-1 encephalitis (HIVE). Human monocyte-derived macrophages (MDMs) infected with HIV-1ADA were injected stereotactically into the caudate and putamen of SCID mice, generating HIVE. These brain subregions are among those most affected in humans. Impaired synaptic transmission and long-term potentiation (LTP) were detected in the CA1 region of hippocampal brain slices of HIVE mice. Memantine-treated HIVE mice showed significant improvements in synaptic function during frequency facilitation tests and LTP induced by high-frequency stimulation when compared with untreated animals. Immunocytochemical measures of neuronal antigens mirrored the neuronal physiological tests. These results demonstrate that memantine attenuates hippocampal synaptic impairment in murine HIVE and provide a rationale for its use in infected humans who experience cognitive decline.

Original languageEnglish (US)
Pages (from-to)7194-7198
Number of pages5
JournalJournal of Neuroscience
Volume24
Issue number32
DOIs
StatePublished - Aug 11 2004

Fingerprint

Memantine
Encephalitis
HIV-1
SCID Mice
Long-Term Potentiation
Hippocampal CA1 Region
Putamen
Brain
Neuroprotective Agents
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Dementia
Alzheimer Disease
Macrophages
HIV
Antigens

Keywords

  • HIV-1 encephalitis
  • Hippocampal slices
  • Memantine
  • Monocyte-derived macrophages
  • Neuroprotection
  • Severe combined immunodeficient mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Memantine protects hippocampal neuronal function in murine human immunodeficiency virus type 1 encephalitis. / Anderson, Eric R.; Gendelman, Howard Eliot; Xiong, Huangui.

In: Journal of Neuroscience, Vol. 24, No. 32, 11.08.2004, p. 7194-7198.

Research output: Contribution to journalArticle

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