Human immunodeficiency virus (HIV) infection continues to rise in drug-abusing populations and causes a dementing illness in a subset of individuals. Factors contributing to the development of dementia in this population remain unknown. We found that HIV-infected individuals with the E4 allele of Apolipoprotein E (ApoE) or history of intravenous drug abuse had increased oxidative stress in the CNS. In vitro studies showed that HIV proteins, gp120 and Tat, Tat + morphine but not tumor necrosis factor-alpha (TNF-alpha), caused increased neurotoxicity in human neuronal cultures with ApoE4 allele. Microarray analysis showed a differential alteration of transcripts involved in energy metabolism in cultures of ApoE3 and 4 neurons upon treatment with Tat + morphine. This was confirmed using assays of mitochondrial function and exposure of the neurons to Tat + morphine. Using this in vitro model, we screened a number of novel antioxidants and found that only L-deprenyl and diosgenin protected against the neurotoxicity of Tat + morphine. Furthermore, Tat-induced oxidative stress impaired morphine metabolism which could also be prevented by diosgenin. In conclusion, opiate abusers with HIV infection and the ApoE4 allele may be at increas...Continue Reading
Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity
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Morphine could increase apoptotic factors in the nucleus accumbens and prefrontal cortex of rat brain's reward circuitry
Morphine potentiates neurodegenerative effects of HIV-1 Tat through actions at μ-opioid receptor-expressing glia
Fractalkine/CX3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death
A growth factor attenuates HIV-1 Tat and morphine induced damage to human neurons: implication in HIV/AIDS-drug abuse cases
Effect of maternal morphine sulfate exposure on neuronal plasticity of dentate gyrus in Balb/c mice offspring
Depressed neurofilament expression associates with apolipoprotein E3/E4 genotype in maturing human fetal neurons exposed to HIV-1
5α-reduced progestogens ameliorate mood-related behavioral pathology, neurotoxicity, and microgliosis associated with exposure to HIV-1 Tat
Alzheimer's Disease: APP, Gamma Secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System
Morphine treatment of human monocyte-derived macrophages induces differential miRNA and protein expression: impact on inflammation and oxidative stress in the central nervous system
Human immunodeficiency virus-associated neurocognitive disorder: pathophysiology in relation to drug addiction
The Potential of Sub-Saharan African Plants in the Management of Human Immunodeficiency Virus Infections: A Review
Identification of putative biomarkers for HIV-associated neurocognitive impairment in the CSF of HIV-infected patients under cART therapy determined by mass spectrometry
Dihydrodiosgenin protects against experimental acute pancreatitis and associated lung injury through mitochondrial protection and PI3Kγ/Akt inhibition
Stereological study of the effects of morphine consumption and abstinence on the number of the neurons and oligodendrocytes in medial prefrontal cortex of rats
Apolipoprotein E4 Suppresses Neuronal-Specific Gene Expression in Maturing Neuronal Progenitor Cells Exposed to HIV
Morphine-alcohol treatment impairs cognitive functions and increases neuro-inflammatory responses in the medial prefrontal cortex of juvenile male rats
The effect of a neuroprotective dose of isatin or deprenyl to mice on the profile of brain isatin-binding proteins
Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances
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