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

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Cognitive impairment in human immunodeficiency virus type 1-associated dementia (HAD) is linked to hippocampal alterations.
• The precise mechanisms underlying these physiological changes remain poorly understood.

Purpose of the Study:

• To investigate the impact of viral infection and macrophage activation on synaptic transmission and plasticity in the hippocampus.
• To elucidate the neuronal mechanisms contributing to cognitive dysfunction in human immunodeficiency virus type 1 encephalitis (HIVE).

Main Methods:

• Utilized a severe combined immunodeficiency mouse model of HIVE, induced by stereotactic injection of HIV-1-infected human monocyte-derived macrophages (MDM).
• Assessed hippocampal neuronal physiology in HIVE and sham-injected mice at 3, 7, and 15 days post-injection.
• Recorded electrically evoked field excitatory postsynaptic potentials in the CA1 region, evaluating input-output relationships, paired-pulse facilitation (PPF), and long-term potentiation (LTP).

Main Results:

• HIVE mice required higher stimulation intensity for synaptic responses and exhibited deficits in PPF at all measured time points.
• Impaired induction and maintenance of LTP were observed in HIVE mice compared to controls.
• MDM-injected mice showed intermediate synaptic changes, suggesting a role for both viral components and activated macrophages.

Conclusions:

• HIV-1 infection and associated macrophage activation significantly alter hippocampal synaptic transmission and plasticity.
• These synaptic changes in the HIVE mouse model provide insights into the pathophysiology of cognitive deficits seen in human HAD.
• Further research into these mechanisms could inform therapeutic strategies for neurological complications of HIV-1 infection.