Nigral degeneration in acquired immune deficiency syndrome (AIDS)

Reyes, Marc G.; Faraldi, Francesco; Senseng, C S; Flowers, Calvin; Fariello, Ruggero G.

doi:10.1007/bf00310921

Cited by 127 publications

(85 citation statements)

References 12 publications

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“…Histopathological studies, demonstrating the presence of high concentrations of viral proteins in the striatum of HIV-1 seropositive patients coupled to abnormalities of the pars compacta of the SN even in the absence of clinical evidence of parkinsonism (46,47), corroborate the physiopathological implications of our findings obtained in both a cell and an animal model. In this respect, it has been recently shown that Tat can easily across the blood-brain barrier (48).…”

Section: Induction Of a Subclinical Parkinson's-like Disease Insupporting

confidence: 88%

HIV-1 Tat-mediated Inhibition of the Tyrosine Hydroxylase Gene Expression in Dopaminergic Neuronal Cells

Zauli¹,

Secchiero²,

Rodella³

et al. 2000

Journal of Biological Chemistry

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Treatment of dopaminergic rat PC12 cells with human immunodeficiency virus, type 1 (HIV-1) Tat protein or tat cDNA inhibited the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for the dopamine biosynthetic pathway, as well as the production and release of dopamine into the culture medium. Moreover, the Tat addition to PC12 cells up-regulated the expression of the inducible cAMP early repressor (ICER), a specific member of the cAMP-responsive element modulator transcription factor family, in a cAMP-dependent manner. In turn, ICER overexpression abrogated the transcription activity of the TH promoter in PC12 cells, strongly suggesting ICER involvement in Tat-mediated inhibition of TH gene expression. In vivo injection of synthetic HIV-1 Tat protein into the striatum of healthy rats induced a subclinical Parkinson's-like disease that became manifested only when the animals were treated with amphetamine. As early as one week postinjection, the histochemical examination of the rat substantia nigra showed a reduced staining of neurons expressing TH followed by a loss of TH ؉ neurons at later time points. As Tat protein can be locally released into the central nervous system by HIV-1-infected microglial cells, our findings may contribute to the explanation of the pathogenesis of the motorial abnormalities often reported in HIV-1 seropositive individuals.

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Section: Induction Of a Subclinical Parkinson's-like Disease Insupporting

confidence: 88%

HIV-1 Tat-mediated Inhibition of the Tyrosine Hydroxylase Gene Expression in Dopaminergic Neuronal Cells

Zauli¹,

Secchiero²,

Rodella³

et al. 2000

Journal of Biological Chemistry

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“…Studies investigating substances of abuse and HIV infection suggest that drugs accelerate neuronal loss in HIV infection, and that dopamine, in addition to its typical neurotransmission role, can alter BBB integrity and promote leukocyte activation (see Substance abuse, HIV, and the BBB for a more comprehensive discussion of dopamine) (Reyes et al 1991;Bennett et al 1995;Herz 1995;Czub et al 2004;Wang et al 2004). …”

Section: Neurotransmitters Originating From the Cns Or Blood Acting Omentioning

confidence: 99%

Neuroimmunity and the Blood–Brain Barrier: Molecular Regulation of Leukocyte Transmigration and Viral Entry into the Nervous System with a Focus on NeuroAIDS

Buckner

Luers

Calderon

et al. 2006

Jrnl NeuroImmune Pharm

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HIV infection of the central nervous system (CNS) can result in neurologic dysfunction with devastating consequences in a significant number of individuals with AIDS. Two main CNS complications in individuals with HIV are encephalitis and dementia, which are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, bloodbrain barrier (BBB) disruption, and eventual damage and/or loss of neurons. One of the major mediators of NeuroAIDS is the transmigration of HIV-infected leukocytes across the BBB into the CNS. This review summarizes new key findings that support a critical role of the BBB in regulating leukocyte transmigration. In addition, we discuss studies on communication among cells of the immune system, BBB, and the CNS parenchyma, and suggest how these interactions contribute to the pathogenesis of Neuro-AIDS. We also describe some of the animal models that have been used to study and characterize important mechanisms that have been proposed to be involved in HIV-induced CNS dysfunction. Finally, we review the pharmacologic interventions

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“…During active infection, these structures contain among the brain's highest viral burden as well as HIV-1-infected macrophages and multinucleated giant cells (Kure et al 1990), which cause loss of dopaminergic neurons in the substantia nigra (Reyes et al 1991) and striatal atrophy (Berger and Nath 1997). Signs of parkinsonism have also been observed in the Ôacquired immune deficiency sydrome (AIDS)-dementia complexÕ (Mirsattari et al 1998).…”

mentioning

confidence: 99%

Human immunodeficiency virus‐1 Tat protein and methamphetamine interact synergistically to impair striatal dopaminergic function

Maragos¹,

Young²,

Turchan³

et al. 2002

Journal of Neurochemistry

116

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The human immunodeficiency virus (HIV)-1 transactivating protein Tat may be pathogenically relevant in HIV-1-induced neuronal injury. The abuse of methamphetamine (MA), which is associated with behaviors that may transmit HIV-1, may damage dopaminergic afferents to the striatum. Since Tat and MA share common mechanisms of injury, we examined whether co-exposure to these toxins would lead to enhanced dopaminergic toxicity. Animals were treated with either saline, a threshold dose of MA, a threshold concentration of Tat injected directly into the striatum, or striatal injections of Tat followed by exposure to MA. Threshold was defined as the highest concentration of toxin that would not result in a significant loss of striatal dopamine levels. One week later, MA-treated animals demonstrated a 7% decline in striatal dopamine levels while Tat-treated animals showed an 8% reduction. Exposure to both MA + Tat caused an almost 65% reduction in striatal dopamine. This same treatment caused a 56% reduction in the binding capacity to the dopamine transporter. Using human fetal neurons, enhanced toxicity was also observed when cells were exposed to both Tat and MA. Mitochondrial membrane potential was disrupted and could be prevented by treatment with antioxidants. This study demonstrates that the HIV-1 ÔvirotoxinÕ Tat enhances MAinduced striatal damage and suggests that HIV-1-infected individuals who abuse MA may be at increased risk of basal ganglia dysfunction.

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Nigral degeneration in acquired immune deficiency syndrome (AIDS)

Cited by 127 publications

References 12 publications

HIV-1 Tat-mediated Inhibition of the Tyrosine Hydroxylase Gene Expression in Dopaminergic Neuronal Cells

HIV-1 Tat-mediated Inhibition of the Tyrosine Hydroxylase Gene Expression in Dopaminergic Neuronal Cells

Neuroimmunity and the Blood–Brain Barrier: Molecular Regulation of Leukocyte Transmigration and Viral Entry into the Nervous System with a Focus on NeuroAIDS

Human immunodeficiency virus‐1 Tat protein and methamphetamine interact synergistically to impair striatal dopaminergic function

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