HIV-1gp120 induces neuronal apoptosis through enhancement of 4-aminopyridine-senstive outward K+ currents.

Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) usually occurs late in the course of HIV-1 infection and the mechanisms underlying HAD pathogenesis are not well understood. Accumulating evidence indicates that neuronal voltage-gated potassium (Kv) channels play an important role in memory processes and acquired neuronal channelopathies in HAD. To examine whether Kv channels are involved in HIV-1-associated neuronal injury, we studied the effects of HIV-1 glycoprotein 120 (gp120) on outward K+ currents in rat cortical neuronal cultures using whole-cell patch techniques.

Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain.

The studies presented here demonstrate the protective effect of acetyl-L-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals.

Methamphetamine abuse, HIV infection, and neurotoxicity.

Methamphetamine (Meth) use and human immunodeficiency virus (HIV) infection are major public health problems in the world today. Ample evidence indicates that HIV transfection risk is greatly enhanced with Meth use. Studies have shown that both HIV infection and Meth abuse can cause neuronal injury leading to neurodegeneration.

Involvement of the 4-aminopyridine-sensitive transient A-type K+ current in macrophage-induced neuronal injury.

Through their capacity to secrete, upon activation, a variety of bioactive molecules, brain macrophages (and resident microglia) play an important role in brain immune and inflammatory responses. To test our hypothesis that activated macrophages induce neuronal injury by enhancing neuronal outward K(+) current, we studied the effects of lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophage (MDM) on neuronal transient A-type K(+) current (I(A)) and resultant neuronal injury in primary rat hippocampal neuronal cultures. Bath application of LPS-stimulated MDM-conditioned media (MCM+) enhanced neuronal I(A) in a concentration-dependent manner.

4-Aminopyridine improves spatial memory in a murine model of HIV-1 encephalitis.

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.

Voltage-gated potassium channels in human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorders.

Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD), a severe form of HIV-associated neurocognitive disorders (HAND), describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (brain perivascular macrophages and microglia) releasing immune and viral products in the brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways.

Pathogenesis of Human Immunodeficiency Virus Type-1 (HIV-1)-Associated Dementia: Role of Voltage-Gated Potassium Channels.

HIV-1-associated dementia (HAD) describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the incidence of HAD has decreased significantly in the era of HAART, it remains a significant complication of HIV-1 infection as patients with acquired immune deficient syndrome (AIDS) live longer, antiretroviral drugs remain unable to effectively cross the blood-brain barrier (BBB), and HIV-1 resistance grows due to viral strain mutation. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (MP; brain perivascular macrophages and microglia) releasing immune and viral products in brain.

Voltage-gated potassium channel modulation of neurotoxic activity in human immunodeficiency virus type-1(HIV-1)-infected macrophages.

Macrophages play an important role in brain immune and inflammatory responses. They are also critical cells in mediating the pathology of neurodegenerative disorders such as HIV-associated dementia. This is largely through their capacity to secrete a variety of bioactive molecules such as cytokines, leading to neuronal dysfunction and/or death.

Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory.

Learning and memory depend upon poorly defined synaptic and intracellular modifications that occur in activated neurons. Mitogen activated protein kinase-extracellular regulated kinase (MAPK-ERK) signaling and de novo protein synthesis are essential aspects of enduring memory formation, but the precise effector molecules of MAPK-ERK signaling in neurons are not well defined. Early growth response (Egr) transcriptional regulators are examples of MAPK-ERK regulated genes and Egr1 (zif268) has been widely recognized as essential for some aspects of learning and memory.