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P Riederer

Publications and source records attributed to P Riederer.

At least 73 records · Page 4Linked to original sources
PubMed2002

Increased hippocampal DNA oxidation in serotonin transporter deficient mice.

The serotonin transporter (5HTT) is the molecule responsible for the high-affinity reuptake of 5HT from the synaptic cleft. Mice lacking the 5HTT exhibit highly elevated extracellular concentrations of 5HT. We assessed whether the glutathione detoxification system is altered in 5HTT-deficient mice. While levels of reduced and oxidized glutathione were unchanged, glutathione metabolising enzymes showed a differential pattern of modulation. Glutathione peroxidase was reduced in frontal cortex, brainstem, and cerebellum of 5HTT-deficient mice, though not to a statistically significant extent, while a putative isoform of the detoxifying enzyme glutathione-S-transferase pi was decreased in a number of brain regions, especially in brainstem. At the level of the DNA, we found an increase of oxidative DNA adducts in the hippocampus of 5HTT-deficient mice. Given the importance of the hippocampus in learning and memory, this may be the most important neurochemical consequence of the absence of the 5HTT.

Animals↗
PubMed2002

Methylmercury induces neurite degeneration in primary culture of mouse dopaminergic mesencephalic cells.

Methylmercury cation (MeHg) is an hazardous environmental pollutant with neurotoxic action. Little is known about the effects of MeHg on catecholaminergic neurons. In the present study we have used epifluorescence microscopy and confocal microscopy to investigate the alterations induced by MeHg in primary DA (dopaminergic) cells isolated from the ventral mesencephalon of CD-1 embryonic mice and cultured for six days in vitro. DA cells were identified in the multi-culture by immunocytochemistry using a tyrosine-hydroxylase antibody. The morphometric analysis of DA neurons exposed to 1 microM MeHg demonstrated a striking decrease in the number of neurites, indicative of cytoskeletal alteration. In addition, DA neurons displayed cell shrinkage and a significant increase of nuclei with chromatin condensation. Based on these results it is concluded that MeHg is highly toxic to primary DA neurons.

Animals↗
PubMed2002

Macaque animal model for HIV-induced neurological disease.

The pathogenesis of HIV-induced neurological disorders is still incompletely understood. Since many aspects of this disease are difficult to explore in humans, animal models are necessary to fill the gaps in our knowledge. Based on the high concordance with the human system, the SIV-infection of macaques currently provides the best animal model to study pathogenesis, therapy and prevention of HIV-infection. In this review, important features of the CNS-infection in this model are outlined. Recent virological, immunological, neurophysiological and neurochemical findings obtained with this animal model are presented and key factors in the development of neurological disease are identified.

AIDS Dementia Complex↗
PubMed2002

Parkinsonism in HIV dementia.

A great number of human immunodeficiency virus (HIV)-infected patients develop a central nervous system disorder, commonly called HIV dementia or AIDS dementia complex (ADC). HIV dementia is independent of opportunistic infections and is due to the virus itself. Symptoms include psychomotor slowing, apathy and motor disorders similar to the bradykinesia and postural and gait abnormalities observed in late Parkinson's disease. Consequently, HIV has been discussed during the last few years as an additional cause for parkinsonism, and parkinsonian syndromes as manifestations of HIV dementia. Moreover, the early phase of HIV infection gains increasing interest because of studies which report subtle neurological symptoms at this stage. Accordingly, we found in SIV-infected monkeys that dopamine is reduced by 44% within as few as two months of infection, indicating that changes during early infection must be thoroughly evaluated. In this short review, we discuss alterations in the nigrostriatal dopaminergic system during early and late immunodeficiency virus infection and the common clinical and biochemical features shared by HIV dementia and Parkinson's disease.

AIDS Dementia Complex↗
PubMed2002

Different modes of action of catecholamine-O-methyltransferase inhibitors entacapone and tolcapone on adenylyl cyclase activity in vitro.

Catechol-O-methyltransferase (COMT) inhibitors such as entacapone and tolcapone are used as adjuncts to L-DOPA ( l-3,4-dihydroxyphenylalanine, levodopa) in the treatment of Parkinson's disease. Tolcapone has been reported to associate with diarrhoea, a common reason for study withdrawal. The mechanism of this adverse effect is not yet understood. Cholera toxin causes diarrhoea by permanent activation of G(s) proteins, resulting in increased adenylyl cyclase (AC) activity. The aim of this study was to examine the effects of the COMT inhibitors entacapone and tolcapone on AC activity in membranes isolated from rat striatum, a brain structure enriched with dopaminergic G-protein-coupled receptors and AC activity. This study demonstrates differential effects of tolcapone and entacapone on Gpp(NH)p/dopamine-stimulated AC activity. Entacapone enhanced the stimulatory effect of Gpp(NH)p/dopamine, whereas tolcapone attentuated this effect, suggesting that diarrhoea associated with tolcapone treatment is not caused by permanent activation of G(s) proteins.

Adenylyl Cyclase Inhibitors↗
PubMed2002

Evolutionary conserved microsatellites in the promoter region of the 5-hydroxytryptamine receptor 2C gene (HTR2C) are not associated with bipolar disorder in females.

Two polymorphic dinucleotide repeats separated by a short spacer are localized in the promoter region of the serotonin receptor 2C gene ( HTR2C). One of the repeats was found to be evolutionary conserved between humans and rhesus monkeys. Although promoter-associated microsatellites have previously been shown to regulate expression of different genes, we did not find any significant influence of distinct HTR2C promoter microsatellite alleles on transcriptional efficiency as measured by luciferase activity and receptor availability as assayed by [(3)H]-mesulergine binding. Furthermore, no association of specific alleles with bipolar disorder was found. These results indicate that the HTR2C promoter polymorphism does not contribute significantly to the etiopathogenesis of bipolar disorder in females.

Aged↗
PubMed2002

Mini-review: multiple developmental forms of parkinsonism. The basis for further research as to the pathogenesis of parkinsonism.

A range of extrapyramidal disturbances have been reported in children following early brain damage. In adults, damage to the basal ganglia can elicit abnormal motor activity in either direction; it would seem reasonable that the same would apply to damage occurring at an earlier developmental stage. The Viennese paediatrician Widhalm described a hypokinetic/parkinsonoid syndrome ("infantile hypokinetic-hypertonic syndrome with Parkinson symptomatic") presented by a significant minority of the children with extrapyramidal movement disturbances, corresponding to the mild rigid-akinetic type of Parkinson's disease. In contrast to classical parkinsonism, but consistent with some forms of post-encephalitic parkinsonism, the syndrome was reversible, although only after L-DOPA therapy. Widhalm's observation that at least one form of childhood parkinsonism can be cured with L-DOPA also suggests that the amino acid plays a more active role than mere replacement therapy in children, perhaps also acting as a neurotrophic agent. It is proposed that environmental factors, including viral and risk factors associated with pregnancy and birth, together with genetically determined lability, may increase the incidence of early hypokinesia/parkinsonism in particular and of Parkinson's disease in later life by disturbing the immature basal ganglia at critical developmental stages. The spectrum disorder of Parkinson's disease thereby occurs as a number of various etiopathologically distinct syndrome subtypes, including early onset developmental forms caused by in utero or early post partum trauma.

Basal Ganglia↗
PubMed2002

Degeneration of neuronal cells due to oxidative stress--microglial contribution.

Various neurodegenerative disorders including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis have been causally linked to the generation of free radicals and oxidative stress. In this review, we discuss the implication of oxidative stress in neuronal death and point out the role of intracellular signaling pathways leading to activation of transcription factors associated with cell death and repair. In particular, the impact of microglia as contributors in promoting oxidative stress in neurodegeneration is highlighted. Finally, pivotal molecular targets for drug therapies of brain disorders are reported.

Animals↗
PubMed2002

Psychiatric complications in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) infection is associated with psychiatric complications, including cognitive impairment, affective disorders, and psychosis. These psychiatric complications impair quality of life, affect disease prognosis, and impede treatment by compromising medication adherence. They also increase the likelihood of HIV transmission, either directly or via their high prevalence rate among drug abusers. In this article, the authors provide a brief overview of the most common psychiatric complications associated with HIV infection and discuss the role of dopamine as a link between psychiatric manifestations and the progression of immunodeficiency infection.

AIDS Dementia Complex↗
PubMed2001

Advanced glycation endproducts change glutathione redox status in SH-SY5Y human neuroblastoma cells by a hydrogen peroxide dependent mechanism.

The reaction of proteins with reducing sugars leads to the formation of 'advanced glycation endproducts' (AGEs). They accumulate in Alzheimer's disease brain in the vicinity of beta-amyloid plaques. AGEs are cytotoxic by a mechanism involving reactive oxygen species, which implies that they could compromise glutathione redox status. In this study, we show that AGEs (BSA-AGE and beta-amyloid-AGE) persistently increase the ratio of oxidized to reduced glutathione in a dose- and time-dependent manner in SH-SY5Y neuroblastoma cells. The level of oxidized glutathione accounted to 10-14% and persisted for up to 24 h in the presence of added AGEs. In contrast, the unmodified beta-amyloid peptides A beta (1-40) and A beta (25-35) had no significant effect on glutathione redox status. The AGE-induced increase in oxidized glutathione could be prevented by the radical scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AGE-mediated depletion of reduced glutathione.

Alzheimer Disease↗
PubMed2001

Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses.

Disturbed neural development has been postulated as a crucial factor in the pathophysiology of schizophrenic psychoses. The neurobiochemical basis for such changes of cytoarchitecture and changed neural plasticity could involve an alteration in the regulation of neurotrophic factors. In order to test this hypothesis, BDNF and NT-3 levels in post-mortem brain tissue from schizophrenic patients were determined by ELISA. There was a significant increase in BDNF concentrations in cortical areas and a significant decrease of this neurotrophin in hippocampus of patients when compared with controls. NT-3 concentrations of frontal and parietal cortical areas were significantly lower in patients than in controls. These findings lend further evidence to the neurotrophin hypothesis of schizophrenic psychoses which proposes that alterations in expression of neurotrophic factors could be responsible for neural maldevelopment and disturbed neural plasticity, thus being an important event in the etiopathogenesis of schizophrenic psychoses.

Aged↗
PubMed2001

Regional and age-dependent expression of the nitric oxide receptor, soluble guanylyl cyclase, in the human brain.

Nitric oxide (NO), synthesized by neuronal NO synthase (NOS-I), plays essential physiological roles in the brain. The major molecular target for NO is soluble guanylyl cyclase (sGC), a heterodimeric hemoprotein composed of a larger alpha and a smaller beta subunit. Both subunits of sGC are needed to generate the second messenger cyclic GMP (cGMP). Here we show using subunit-specific antibodies and Western blot analysis that sGCalpha1 and sGCbeta1 protein subunits are present in all examined human brain regions. The relative distribution of the two subunits was similar and also correlated well with the known distribution of NOS-I. The highest expression levels of sGC were found in cortex, basal ganglia and the limbic system. These regions display the most prominent biochemical and histological changes during ageing. In cortex, a negative correlation between the amounts of sGC and age was found, while sex and post-mortem delay time did not affect sGC levels significantly. Our data suggest that sGCalpha1 and sGCbeta1 subunits are widely distributed in human brain, consistent with a major role in NO signaling. Moreover, the NO/cGMP pathway appears to be affected by ageing in the human brain.

Aged↗
PubMed2001

Nitroxyl oxidizes NADPH in a superoxide dismutase inhibitable manner.

Nitric oxide synthases (NOS) convert L-arginine and N(omega)-hydroxy-L-arginine to nitric oxide (*NO) and/or nitroxyl (NO(-)) in a NADPH-dependent fashion. Subsequently, *NO/superoxide (O(2-)-derived peroxynitrite (ONOO(-)) consumes one additional mol NADPH. The related stoichiometry of NO(-) and NADPH is unclear. We here describe that NO(-) also oxidizes NADPH in a concentration-dependent manner. In the presence of superoxide dismutase (SOD), which also converts NO(-) to *NO, nitrite accumulation was almost doubled and no oxidation of NADPH was observed. Nitrate yield from NO(-) was low, arguing against intermediate ONOO(-) formation. Thus, biologically formed NO(-) may function as an effective pro-oxidant unless scavenged by SOD and affect the apparent NADPH stoichiometry of the NOS reaction.

Free Radicals↗
PubMed2001

Increased levels of calcium-sensitive adenylyl cyclase subtypes in the limbic system of alcoholics: evidence for a specific role of cAMP signaling in the human addictive brain.

We examined the amounts of several adenylyl cyclase (AC) isoforms and of cAMP-response element binding protein (CREB) in alcoholic and control brains. Immunoreactivity of type I AC was significantly increased in alcoholic nucleus accumbens and corpus amygdaloideum. Immunoreactivity of type VIII AC was also increased in alcoholic corpus amygdaloideum and hippocampus. CREB immunoreactivities were unchanged. These findings indicate that the brain-region specific increase of Ca(2+)-sensitive AC may contribute to the pathophysiology of alcoholism.

Adenylyl Cyclases↗
PubMed2001

The human dopamine transporter gene: the 5'-flanking region reveals five diallelic polymorphic sites in a Caucasian population sample.

The 5'-flanking region of the human dopamine transporter (hDAT) was systematically screened for variants by single strand conformation analysis (SSCA) between -1586 and +97 basepair (bp) relative to the transcription start site. Five diallelic polymorphisms were found, which were shown to be due to single base substitutions: T-67A, G-660C, C-839T, C-1169G, T-1476G. In a population sample of 119 unrelated Caucasians, allele frequencies of the rarer allele were 47% for -67T, 3% for -660C, 45% for -839T, 50% for -1169G, and 8% for -1476G, respectively. Among 15 observed haplotypes, seven haplotypes collected a frequency of about 96% in our sample. T-67A, C-839T, C-1169G, T-1476G were related to potential transcriptional recognition sites. These findings and the occurrence of distinct haplotypes at the hDAT promoter locus in a Caucasian population sample make this region a promising target in the context of linkage and association studies in certain diseases.

5' Untranslated Regions↗
PubMed2001

Selegiline completely restores choline acetyltransferase activity deficits in simian immunodeficiency infection.

Human immunodeficiency virus (HIV) infection is associated with a progressive dementia, in addition to motor and behavioural deficits. Cognitive deterioration and motor impairments have been observed also in simian immunodeficiency virus (SIV)-infected monkeys, an animal model for HIV infection. We found recently that choline acetyltransferase activity is markedly reduced in brains of SIV-infected monkeys. We report now that selegiline, completely restores the reduced choline acetyltransferase activity which encourages for a meaningful anti-dementia therapeutic strategy.

Animals↗
PubMed2001

The neuronal calcium sensor protein VILIP-1 is associated with amyloid plaques and extracellular tangles in Alzheimer's disease and promotes cell death and tau phosphorylation in vitro: a link between calcium sensors and Alzheimer's disease?

To investigate whether the observed association of intracellular neuronal calcium sensor (NCS) proteins with amyloid plaques and neurofibrillar tangles in Alzheimer brains is linked to a possible neuroprotective or neurotoxic activity of the protein, we performed cytotoxicity tests in PC12 cells transfected with the calcium sensor protein VILIP-1 (visinin-like protein) and the calcium buffer protein calbindin-D28K. Whereas VILIP-1 expression enhanced the neurotoxic effect of ionomycin already at low ionophore concentrations, calbindin-D28K protected against ionomycin-induced cytotoxicity only at high ionomycin and therefore calcium concentrations. However, in double-transfected cells calbindin-D28K rescued VILIP-1-mediated cytotoxicity at low ionomycin concentrations. Since VILIP-1 was found to be associated with fibrillar tangles in Alzheimer brains, we tested whether VILIP-1 has an influence on tau hyperphosphorylation. VILIP-1 expression enhanced hyperphosphorylation of tau protein compared to nontransfected or calbindin-D28K-transfected cells. These results raise the possibility that the observed reduction in VILIP-1-expressing cells may indicate a selective vulnerability of these neurons and that the calcium sensor protein is involved in the pathophysiology of Alzheimer's disease. The calcium sensor protein may influence tau phosphorylation and have a role in calcium-mediated neurotoxicity opposed to the previously discovered protective effect of calcium buffer proteins.

Alzheimer Disease↗