Antioxidant enzyme dysfunction in monocytes and CSF of Hispanic women with HIV-associated cognitive impairment

Velázquez, Ixane; Plaud, Marines; Wojna, Valerie; Skolasky, Richard L.; Laspiur, J. Pérez; Meléndez, Loyda M.

doi:10.1016/j.jneuroim.2008.10.013

Cited by 35 publications

(36 citation statements)

References 44 publications

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“…In the post-HAART era, female gender as a predictor for progression of HAND has not been previously reported. This may be in part owing to a finding that women with HAND have decreased function and activity of antioxidant enzymes in CSF and monocytes, thus possibly resulting in more oxidative stress in the CNS and thereby promoting peroxynitrite formation and neuronal damage [31,32]. On further analysis of this subset, we did find that women had significantly fewer years of education compared with men, which may explain their worsening HAND status.…”

Section: Discussionmentioning

confidence: 79%

Comparison of Scales to Evaluate the Progression of Hiv-Associated Neurocognitive Disorder

Gandhi

Moxley²,

Creighton³

et al. 2010

HIV Ther.

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Aim-First, to compare the characterization of neurocognitive deficits in milder stages of HIVassociated neurocognitive disorder (HAND) derived from existing dementia rating scales of the American Academy of Neurology (AAN) and Memorial Sloan Kettering (MSK) with the 2007 consensus ('Frascati') classification. Second, to identify potential sociodemographic and clinical predictors of HAND progression during 1-year follow-up.Methods-104 HIV-infected subjects in an existing cohort system were evaluated with a medical history, exam, neuropsychological test battery and functional assessments. The degree of HAND was rated using the AAN, MSK and Frascati scales. The degree of concordance among these scales was determined. In addition, 45 subjects were reassessed for changes in their neurocognitive status at 1-year follow-up. Associations between age, education, sex, depression ratings, substance abuse, race, hepatitis C serostatus, CD4 count and progression of HAND were examined.Results-There was excellent concordance (γ > 0.8) among the Frascati, MSK and AAN ratings. Subjects rated as having minor cognitive motor disorder on the AAN scale (n = 45) were evenly split between Frascati rating of asymptomatic neurocognitive impairment (n = 24) and mild neurocognitive disorder (n = 21). At 1-year follow-up of 45 subjects, 31% had worsened, 13% had improved and 56% were stable. Predictors of progression included age older than 50 years (odds ratio: 5.57; p = 0.013) and female gender (odds ratio: 3.13; p = 0.036). Conclusion-TheFrascati HAND rating scale has excellent concordance with previous neurocognitive rating scales and can be used to better characterize milder stages of cognitive impairment. Older individuals and women appeared to be more likely to show neurocognitive progression. † Author for correspondence: Tel.: +1 443 287 3313, Fax: +1 443 287 3312, ngandhi@jhmi.edu. Ethical conduct of researchThe authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investi gations involving human subjects, informed consent has been obtained from the participants involved. Financial & competing interests disclosureThe authors were supported by the Johns Hopkins NIMH Center for Novel Therapeutics in HIV Associated Cognitive Disorder (MH 075673), (MH71150) and (NS 049465). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. One of the earlier scales used to diagnose HIV-associated neurocognitive disorders (HAND) was the Memorial Sloan Kettering (MSK) scale, which contains gradations that range from minor cognitive disturbance to profound and incapacitating disorders [1]. However, the scales...

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Section: Discussionmentioning

confidence: 79%

Comparison of Scales to Evaluate the Progression of Hiv-Associated Neurocognitive Disorder

Gandhi

Moxley²,

Creighton³

et al. 2010

HIV Ther.

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“…Several reports indicate that oxidative stress plays a major role in neuronal damage and cognitive disorders in HIV-infected patients. 62,63 In this study, we observed that reduced oxidative stress could be due to the decreased HIV infection because of release of TIMP1 from the MNP NF. We also observed the effect of free TIMP1 and MNP-bound TIMP1 exposure on the recovery of spine density in HIV-infected neuronal cells.…”

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confidence: 65%

Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

Atluri¹,

Jayant²,

Pilakka-Kanthikeel³

et al. 2016

IJN

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Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood–brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP)-bound tissue inhibitor of metalloproteinase-1 (TIMP1) protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the neuroprotective effect of TIMP1. Therefore, our results suggest that the MNP-bound TIMP1 delivery method across the blood–brain barrier can be used for reducing HIV infectivity in brain tissue and neuronal toxicity in HIV-infected patients.

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“…Similar results were obtained in the CSF of HAND patients and in HIV seropositive patients that are cocaine users where cathepsin B secretion and activity remained at the same levels between experimental and control groups. It has been established that HIV-1 transforms the monocyte plasma membrane proteome (Kadiu et al 2009) and proteomics analysis of CSF demonstrated that reduction of antioxidants enzymes such as Cu/Zn SOD and GPx, have been associated with disease severity (Laspiur et al 2007; Velazquez et al 2009; Angel et al 2012). It is quite possible that an antioxidant imbalance could promote secretion and neurotoxic activity of cathepsin B in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Cocaine Potentiates Cathepsin B Secretion and Neuronal Apoptosis from HIV-Infected Macrophages

Zenón

Segarra

Gonzalez

et al. 2014

J Neuroimmune Pharmacol

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Substance abuse is a risk factor for HIV infection and progression to AIDS. Recent evidence establishes that cocaine use promotes brain perivascular macrophage infiltration and microglia activation. The lysosomal protease cathepsin B is increased in monocytes from patients with HIV dementia and its secretion induces 10-15% of neurotoxicity. Here we asked if cocaine potentiates cathepsin B secretion from HIV-infected monocyte-derived macrophages (MDM) and its effect in neuronal apoptosis. Samples of plasma, CSF, and post-mortem brain tissue from HIV positive patients that used cocaine were tested for cathepsin B and its inhibitors to determine the in vivo relevance of these findings. MDM were inoculated with HIV-1ADA, exposed to cocaine, and the levels of secreted and bioactive cathepsin B and its inhibitors were measured at different time-points. Cathepsin B expression (p<0.001) and activity (p<0.05) increased in supernatants from HIV-infected cocaine treated MDM compared with HIV-infected cocaine negative controls. Increased levels of cystatin B expression was also found in supernatants from HIV-cocaine treated MDM (p<0.05). A significant increase in 30% of apoptotic neurons was obtained that decreased to 5% with the specific cathepsin B inhibitor (CA-074) or with cathepsin B antibody. Cathepsin B was significantly increased in the plasma and post-mortem brain tissue of HIV/cocaine users over non-drug users. Our results demonstrated that cocaine potentiates cathepsin B secretion in HIV-infected MDM and increase neuronal apoptosis. These findings provide new evidence that cocaine synergize with HIV-1 infection in increasing cathepsin B secretion and neurotoxicity.

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Antioxidant enzyme dysfunction in monocytes and CSF of Hispanic women with HIV-associated cognitive impairment

Cited by 35 publications

References 44 publications

Comparison of Scales to Evaluate the Progression of Hiv-Associated Neurocognitive Disorder

Comparison of Scales to Evaluate the Progression of Hiv-Associated Neurocognitive Disorder

Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

Cocaine Potentiates Cathepsin B Secretion and Neuronal Apoptosis from HIV-Infected Macrophages

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