Cerebrospinal Fluid 5-Hydroxytryptamine and 5-Hydroxyindoleacetic Acid in HIV-1 Infection

Kumar, Adarsh; Berger, Joseph; Eisdorfer, Carl; Fernandez, J. B.; Goodkin, Karl; Kumar, Mahendra

doi:10.1159/000054908

Cited by 24 publications

(19 citation statements)

References 30 publications

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“…Recent studies show that the decrease in the levels of dopamine in CSF is exacerbated in HIV-1 infected patients who are also methamphetamine users and dependent [41] . Regarding the status of serotonin in CSF of HIV-1 infected patients, it was found that while concentration of 5-HT was significantly decreased in the HIV-1 infected patients [13] , there was no change in the concentration of 5-HIAA, the major metabolite of 5-HT. However, the levels of CSF 5-HT in HIV-1 infected patients did not relate with depression evaluated with Beck's depression scale during life.…”

Section: Discussionmentioning

confidence: 94%

“…The status of 5-hydroxytryptamine was assessed in an earlier study in CSF of HIV-1 infected patients during life [13] . This study was carried out in a separate group of asymptomatic HIV-1 infected individuals who were among those enrolled in a longitudinal prospective study of neurological complications of HIV-1 infection.…”

Section: Methodsmentioning

confidence: 99%

“…Subsequent findings that in the CNS, high concentrations of virus was present in the hippocampus and basal ganglia, the areas that are rich in dopaminergic activity, led to the concept that deficits in dopamine might be associated with the neurological disorders, cognitive impairment and behavioral changes [11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 Infection and Central Monoamine Neurotransmitters

Kumar¹,

Fernandez²,

Borodowsky³

et al. 2007

American J. of Infectious Diseases

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Human immunodeficiency virus type 1 (HIV-1) enters the central nervous system (CNS) shortly after infection and gets localized in different brain regions, leading to various types of neuropathological problems. It has been hypothesized that HIV-1 infection mediated neuropathogenesis may also adversely affect the activity of the central monoamine neurotransmitters systems, such as dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin), resulting in neurocognitive deficits and mental health problems. However, investigations are scarce with respect to the status of these neurotransmitters in the CNS of HIV-1+ individuals, particularly in those patients who had received antiretroviral therapy (ART) during life. Since, mental health problems and neurocognitive and neuropsychological deficits continue to persist even after ART intervention, it is pertinent to determine the CNS status of the neurotransmitters associated with these functions. We determined the neurotransmitters, dopamine and its metabolite, homovanillic acid (HVA) in different brain regions of a group of autopsied cases of HIV-1+ and HIV-1 negative controls, using highly sensitive CoulArray HPLC-ECD system. Distribution of HIV-1 viral RNA in these brain regions was also measured using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) technology with high sensitivity of detection (<5 copies of RNA). In a separate study we reported measurement of 5-HT (serotonin) and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the cerebrospinal fluid (CSF) obtained during life of neurologically asymptomatic HIV-1 infected patients and controls. A substantial decrease and a wide variation in the concentration of DA as well as its metabolite, homovanillic acid (HVA) was found in the autopsied brain regions of HIV-1 infected individuals. Wide variation was also found in HIV-1 RNA concentrations in different brain regions with no specific pattern observed in any region. Brain regions of HIV-negative individuals showed no detectable viral RNA. Majority of HIV-1+ individuals had demonstrated neurocognitive impairment during life despite ART intervention. A significant decrease in 5-HT concentration was also found in the CSF of HIV-1 infected patients. These studies demonstrate that HIV-1 infection adversely affects the central DA and 5-HT systems.

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Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

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HIV-1 Infection and Central Monoamine Neurotransmitters

Kumar¹,

Fernandez²,

Borodowsky³

et al. 2007

American J. of Infectious Diseases

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“…Kumar et al [28] found that the levels of lumbar CSF 5-HT were significantly lower in the HIV-1 + group compared to the HIV-1 -group, while there was no significant difference in the lumbar CSF 5-HIAA levels between the two groups. These authors also observed that HIV-1 infection affects the CNS 5-HT status with no significant association regarding measures of depression and anxiety at least in the early stage of infection.…”

Section: Discussionmentioning

confidence: 96%

“…Until now, serotonin and 5-hydroxyindoleacetic acid levels have been measured in lumbar cerebrospinal fluid (CSF) of HIV-1-infected individuals [28], but never in ventricular CSF. Neuroendoscopy, a recent minimally invasive neurosurgical technique allows a precise and accurate exploration of all the cerebral ventricles by means of flexible endoscopes [34].…”

Section: Introductionmentioning

confidence: 99%

A Study of Tryptophan Metabolism via Serotonin in Ventricular Cerebrospinal Fluid in HIV-1 Infection Using a Neuroendoscopic Technique

Longatti¹,

Perin²,

Comai³

et al. 2007

CHR

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In this paper we report the study of tryptophan metabolism via serotonin in ventricular CSF in HIV-1 infection in order to investigate the origin of tryptophan metabolites in the human brain. The patients (n=4) were affected with non-communicating hydrocephalus. One of these also was suffering from HIV-1 infection. The CSF was withdrawn from different sites of the cerebral cavity with a neuroendoscopic procedure which allows an accurate exploration of all the cerebral ventricles. The measurement of tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin was carried out by HPLC with fluorometric detection. In HIV-1 infection the highest concentration of tryptophan is present in the CSF of the choroid plexus; however, the levels are markedly lower than those in hydrocephalic individuals (control group). 5-Hydroxytryptophan CSF content is higher in HIV-1 infection than in hydrocephalic controls in all districts examined. Regarding serotonin, a great difference appears in the choroid plexus and in the pituitary recess between the HIV-1 infected patient and the control group. The values of 5-hydroxyindoleacetic acid are much lower in the CSF of the HIV-1 infected patient than in hydrocephalic controls. Melatonin levels appear to fluctuate largely but, in the HIV-1 infection, a great variability is present among the sites of CSF withdrawal. The third ventricle contains the highest concentration of melatonin and the choroid plexus and the pituitary recess the lowest. All the melatonin concentrations in HIV-1 infection are largely different than in hydrocephalic controls. This is the first report on the measurement of tryptophan metabolites via serotonin in ventricular CSF in HIV-1 infection.

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