Substantia nigra hyperechogenicity and CSF dopamine depletion in HIV

Thiermann, J.; Obermann, Mark; Küper, Michael; Kastrup, Oliver; Yaldizli, O.; Eßer, Stefan; Koutsilieri, Eleni; Diener, Hans‐Christoph; Maschke, Matthias

doi:10.1055/s-0028-1086479

Cited by 5 publications

(8 citation statements)

References 28 publications

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“…Collectively, the current behavioral and neurochemical data support clinical data demonstrating subcortical DA vulnerability (Obermann et al. 2009; Paul et al.…”

Section: Discussionsupporting

confidence: 82%

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Hyperdopaminergic tone in HIV‐1 protein treated rats and cocaine sensitization

Ferris¹,

Frederick-Duus²,

Fadel³

et al. 2010

Journal of Neurochemistry

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In the United States, one-third of infected individuals contracted Human Immunodeficiency Virus-1 (HIV-1) via injecting drugs with contaminated needles or through risky behaviors associated with drug use. Research demonstrates concomitant administration of psychostimulants and HIV-1-proteins damage neurons to a greater extent than viral proteins or the drug alone. To model the onset of HIV-1-infection in relation to a history of drug use, the current research compared behavior and extracellular dopamine and metabolite levels following Tat1–86 infusions in animals with and without a history of cocaine (Coc) experience (10 mg/kg; i.p.; 1 injection/day × 9 days). Animals receiving a behaviorally sensitizing regimen of Coc demonstrated a decrease in extracellular dopamine concentration in the nucleus accumbens, consistent with evidence describing up-regulation of dopamine transporter uptake. Contrary to this effect, Tat1–86 microinfusion into the nucleus accumbens following the sensitizing regimen of Coc caused a significant increase in extracellular dopamine levels (nM) within 48 h with no difference in percent of baseline response to Coc. After 72 h, Tat + Coc treated animals demonstrated a blunted effect on potassium-stimulated extracellular dopamine release (percent of baseline) with a corresponding decrease in expression of behavioral sensitization to Coc challenge. A persistent decrease in extracellular dopamine metabolite levels was found across all time-points in Tat-treated animals, regardless of experience with Coc. The current study provides evidence for divergent neurochemical and behavioral outcomes following Tat-treatment; contingent upon experience with Coc.

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“…Collectively, the current behavioral and neurochemical data support clinical data demonstrating subcortical DA vulnerability (Obermann et al. 2009; Paul et al.…”

Section: Discussionsupporting

confidence: 82%

“…2000). DOPAC systems are less variable in the course of HIV‐1 infection (Obermann et al. 2009), and documented HIV‐1‐induced DOPAC alterations are rare.…”

Section: Discussionmentioning

confidence: 99%

Hyperdopaminergic tone in HIV‐1 protein treated rats and cocaine sensitization

Ferris¹,

Frederick-Duus²,

Fadel³

et al. 2010

Journal of Neurochemistry

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“…This finding is consistent with the motor dysfunction pattern in HAND indicating injury of the basal ganglia and the dopaminergic system [29]. Various neuroimaging studies have previously confirmed involvement of the basal ganglia and substantia nigra [5][6][7]20]. With regard to the caudate nucleus, neurocognitive impairment was correlated with volume reduction and reduced blood flow [35].…”

Section: Motor Functionsupporting

confidence: 82%

“…All listed variables were included in the same model. Based on previous brain imaging studies in HIV [7,8,20], regions of interest (ROIs) were selected to detect structural changes within the prefrontal lobe, the occipital lobe, the basal ganglia region and the midbrain. ROIs were derived from a T1 MNI template with help of anatomic automatic labelling toolbox implemented in SPM [21].…”

Section: Regression Analysismentioning

confidence: 99%

Structural gray and white matter changes in patients with HIV

et al. 2011

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In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 ± 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson's Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.

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“…Furthermore, changes in dopaminergic activity in the cerebrospinal fluid (CSF) of HIV-1-infected patients have been found to relate with neurological complications at different stages of disease progression, particularly with a significant decrease in the concentration of dopamine and homovanillic acid (HVA) in the CSF (Berger et al 1994;Larsson et al 1991;Di Rocco et al 2000;Obermann et al 2009) and a decrease of dopamine in the caudate of patients with HIV/AIDS (Sardar et al 1996). In our recent studies, we found that the decrease in dopamine concentration in the CNS of HIV-1-infected individuals is not limited to a few regions in the brain but is significantly decreased in a number of cortical and subcortical regions including frontocortical areas, basal ganglia (BG), caudate, putamen, globus pallidus (GP), and substantia nigra (SN) (Kumar et al 2009).…”

Section: Introductionmentioning

confidence: 98%

Human immunodeficiency virus infection in the CNS and decreased dopamine availability: relationship with neuropsychological performance

et al. 2010

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Human immunodeficiency virus (HIV-1) infection in the central nervous system (CNS) is associated with a wide range of neurological, cognitive, and behavioral problems. HIV-1 enters the brain soon after the initial infection and is distributed in varying concentrations in different regions with specific affinity to the subcortical regions, particularly the basal ganglia, causing neurodegeneration of dopaminergic regions and resulting in the decreased availability of dopamine (DA) in the CNS. Although there are numerous reports on HIV-1-associated neuropsychological (NP) impairment, there is a paucity of studies showing a direct relationship between the decreased availability of dopamine in different regions of postmortem brains of HIV-1-infected individuals and the level of performance in different NP functions during life. Dopamine is the key neurotransmitter in the brain and plays a regulatory role for motor and limbic functions. The purpose of the present study was to investigate the relationship between the decreased availability of dopamine found in the postmortem brain regions (fronto-cortical regions, basal ganglia, caudate, putamen, globus pallidus, and substantia nigra) of individuals with HIV/AIDS and the antemortem level of performance (assessed as T scores) in different NP functions. The relationship between HIV-1 RNA levels in different brain regions and the level of performance in different NP domains was also investigated. We found that although DA concentrations were 2-53% lower in the brain regions of HIV-1-infected, HAART-treated individuals, compared with HIV-negative controls, a 45% decrease in DA levels in the substantia nigra (SN) of HIV-1-infected individuals was significantly correlated with the low level of performance (T scores) in the speed of information processing, learning, memory, verbal fluency, and average T scores across domains. In case of homovanillic acid (HVA), the variable changes in different regions, including the substantia nigra, basal ganglia, caudate, and putamen (compared to that in the HIV-negative individuals), were significantly correlated with the level of performance (T scores) in motor functions, speed of information processing, and attention/working memory. HIVRNA levels in the frontal cortex, caudate, and GP were significantly inversely correlated with abstract/executive function, motor, learning, verbal fluency, and attention/working memory. No significant correlations were found between HIVRNA in other brain regions and NP performance. These findings suggest that the decreased availability of dopamine in the SN (the main site of DA synthesis in the CNS), and changes in the levels of HVA in different brain regions are, in part, related with the lower level of performance in some of the NP functions in individuals with HIV/AIDS.

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Substantia nigra hyperechogenicity and CSF dopamine depletion in HIV

Cited by 5 publications

References 28 publications

Hyperdopaminergic tone in HIV‐1 protein treated rats and cocaine sensitization

Hyperdopaminergic tone in HIV‐1 protein treated rats and cocaine sensitization

Structural gray and white matter changes in patients with HIV

Human immunodeficiency virus infection in the CNS and decreased dopamine availability: relationship with neuropsychological performance

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