Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis

E. R. Anderson, J. Boyle, W. E. Zink, Y. Persidsky, Howard Eliot Gendelman, Huangui Xiong

Research output: Contribution to journalArticle

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Abstract

Alterations in hippocampal physiology affect cognition in human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD). The mechanism for how this occurs is not well understood. To address this, we investigated how changes in synaptic transmission and plasticity are affected by viral infection and macrophage activation using a severe combined immunodeficiency mouse model of human HIV-1 encephalitis (HIVE). HIVE was induced in mice by stereotactic injection of HIV-1-infected human monocyte-derived macrophages (MDM) into the striatum. Animals were sacrificed after 3, 7 and 15 days. Hippocampal slices were prepared from HIV-1, MDM- and sham-injected animals. Electrically evoked field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus. Neuronal physiology was assessed by input-output and by long-term potentiation (LTP) assays. We observed that a higher stimulation intensity (mA) was required to induce a 1-mV response in the HIVE mice (0.32±0.06) compared with shams (0.17±0.01) at day 7. The stimulation intensities at day 15 were 0.44±0.07 and 0.23±0.05 in the HIVE and shams, respectively. An impairment of synaptic function was detected through measuring synaptic responses induced by stimuli with different intensities. Paired-pulse facilitation (PPF) showed deficits in HIVE mice at days 3, 7, and 15. At day 3, PPF ratios were 1.13±0.02 and 1.24±0.04 in HIVE and sham. The induction and maintenance of LTP was also impaired in HIVE mice. The average magnitude of LTP was 131.23±15.26% of basal in HIVE as compared with sham animals of 232.63±24.18%. MDM-injected mice showed an intermediate response. Taken together, the results show a range of neuronal synaptic transmission and plasticity changes in HIVE mice that may reflect the mechanisms of cognitive dysfunction in human HAD.

Original languageEnglish (US)
Pages (from-to)359-369
Number of pages11
JournalNeuroscience
Volume118
Issue number2
DOIs
StatePublished - May 8 2003

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Encephalitis
HIV-1
Long-Term Potentiation
Neuronal Plasticity
Macrophages
Synaptic Transmission
Dementia
Virus Activation
Severe Combined Immunodeficiency
Macrophage Activation
Excitatory Postsynaptic Potentials
Virus Diseases
Cognition
Hippocampus
Maintenance

Keywords

  • CA1
  • Excitatory postsynaptic potential
  • HIV-1-associated dementia
  • Monocyte-derived macrophages
  • SCID mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis. / Anderson, E. R.; Boyle, J.; Zink, W. E.; Persidsky, Y.; Gendelman, Howard Eliot; Xiong, Huangui.

In: Neuroscience, Vol. 118, No. 2, 08.05.2003, p. 359-369.

Research output: Contribution to journalArticle

Anderson, E. R. ; Boyle, J. ; Zink, W. E. ; Persidsky, Y. ; Gendelman, Howard Eliot ; Xiong, Huangui. / Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis. In: Neuroscience. 2003 ; Vol. 118, No. 2. pp. 359-369.
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