Monoamine metabolite levels in CSF of SIV-infected rhesus monkeys (Macaca mulatta)

Koutsilieri, Eleni; Götz, Monika; Sopper, Sieghart; Stahl–Hennig∥, Christiane; Czub, M.P.; Meulen, Volker ter; Riederer, Peter

doi:10.1097/00001756-199712010-00034

Cited by 29 publications

(11 citation statements)

References 9 publications

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“…CSF DA concentration was measured using a reverse-phase high-pressure liquid chromatography system (Agilent 1100, Waldbronn, Germany) and detected by electrochemical detection (Koutsilieri et al 1997). For qualitative and quantitative analyses, we compared retention times and peak heights with those from commercially available standards (Sigma, St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals

et al. 2013

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Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-naïve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 % CI 1.72–8.96; p = 0.001, Fishers exact test). 42.6 % HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 % uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 %, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease.

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Section: Methodsmentioning

confidence: 99%

Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals

et al. 2013

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“…Peaks were recorded by means of an integrator (HP Chem Station 2/3; Agilent). All settings, columns, and solutions were the same as described elsewhere [17]. Qualitative and quantitative analyses were performed by comparing retention times and peak heights with those obtained with commercially available standards (Sigma, St. Louis, MO).…”

Section: Transcranial Sonographymentioning

confidence: 99%

Substantia nigra hyperechogenicity and CSF dopamine depletion in HIV

et al. 2009

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Dopaminergic dysfunction is thought to play a pivotal role in human immunodeficiency virus (HIV)-related dementia. Decreased dopamine (DA) levels in the cerebrospinal fluid (CSF) and neuronal loss in the substantia nigra (SN) have been reported in HIV-infected patients, suggesting nigrostriatal damage. Structural changes detectable as hyperechogenicity in transcranial ultrasound (TCS) scans of the SN have been reported in patients with Parkinson's disease (PD) and other neurological conditions. In this study, we assessed the echomorphology of the SN in 40 HIV-positive patients compared to 40 age- and sex-matched healthy controls and correlated these findings with CSF levels of DA and the metabolites homovanillic acid (HVA) and 3,4-dihydroxy phenylacetic acid (DOPAC) and with neuropsychologic performance. We observed that the SN of HIV-infected patients was hyperechogenic relative to that of controls (0.07 +/- 0.05 vs. 0.04 +/- 0.07 cm(2); mean +/- SEM; P < 0.001) and that this SN hyperechogenicity was correlated with decreased DA levels in the CSF, decreased CD4 cell count, and an impaired performance in the psychopathology assessment scale (AMDP) subtest for drive and psychomobility. An association to CDC stage, duration of HIV infection, or presence of HIV dementia was not observed. Our results indicate changes in the nigrostriatal system in HIV-infected patients that are detectable as hyperechogenic SN precede prominent extrapyramidal symptoms and cognitive dysfunction.

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“…Similarly, CSF homovalinic acid levels are diminished in patients with AIDS and more severely so in patients with AIDS dementia (Larsson et al, 1991;Berger et al, 1994). A study of monoamine metabolites in CSF of asymptomatic SIV infected rhesus macaques showed increased levels of 3,4-dihydroxyphelnyl acetic acid suggesting increased dopamine turn over in early stages of infection (Koutsilieri et al, 1997b).…”

Section: Da Abnormalities In Cerebrospinal Fluid (Csf) Of Patients Wimentioning

confidence: 99%

Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia

et al. 2000

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Infection with the human immunodeficiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.

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Monoamine metabolite levels in CSF of SIV-infected rhesus monkeys (Macaca mulatta)

Cited by 29 publications

References 9 publications

Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals

Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals

Substantia nigra hyperechogenicity and CSF dopamine depletion in HIV

Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia

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