Biomedical subjects

R Bandopadhyay

Publications and source records attributed to R Bandopadhyay.

9 recordsLinked to original sources

PubMed2003

Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies.

Pathological inclusions containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in the tauopathies, which include Alzheimer's disease, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Tau isoform composition and cellular and regional distribution as well as morphology of these inclusions vary in each disorder. Recently, several pathological missense and exon 10 splice-donor site mutations of the tau gene were identified in FTDP-17. Exon 10 codes for the second of four microtubule-binding repeat domains. The splice-site mutations result in increased inclusion of exon 10 which causes a relative increase in tau isoforms containing four microtubule-binding repeat domains over those containing three repeat domains. This could be a central aetiological mechanism in FTDP-17 and, perhaps, other related tauopathies. We have investigated changes in the ratio and distribution of three-repeat and four-repeat tau in the different tauopathies as a basis of the phenotypic range of these disorders and the selective vulnerability of different subsets of neurones. In this study, we have developed two monoclonal antibodies, RD3 and RD4 that effectively distinguish these closely related tau isoforms. These new isoform-specific antibodies are useful tools for analysing tau isoform expression and distribution as well as pathological changes in the human brain.

Animals↗

PubMed2001

No pathogenic mutations in the synphilin-1 gene in Parkinson's disease.

alpha-Synuclein is mutated in rare autosomal dominant forms of Parkinson's disease and is a major component of Lewy bodies and neurites. Synphilin-1, a novel protein interacts in vivo and co-localises with alpha-synuclein in Lewy bodies. We analysed the synphilin-1 gene in familial Parkinson's disease by single-strand conformation polymorphism (SSCP) and automated sequencing but found no coding mutations. However, we identified two novel intronic polymorphisms; an A/T polymorphism in intron 2, resulting in the introduction of an Alu1 site and a second G/T polymorphism in intron 4. We analysed the intron 2 polymorphism for allelic association as it was conducive to rapid screening but observed no changes in frequency between Parkinson's disease cases and controls.

Aged↗

PubMed2001

Contractile proteins in pericytes at the blood-brain and blood-retinal barriers.

Evidence from a variety of sources suggests that pericytes have contractile properties and may therefore function in the regulation of capillary blood flow. However, it has been suggested that contractility is not a ubiquitous function of pericytes, and that pericytes surrounding true capillaries apparently lack the machinery for contraction. The present study used a variety of techniques to investigate the expression of contractile proteins in the pericytes of the CNS. The results of immunocytochemistry on cryosections of brain and retina, retinal whole-mounts and immunoblotting of isolated brain capillaries indicate strong expression of the smooth muscle isoform of actin (alpha-SM actin) in a significant number of mid-capillary pericytes. Immunogold labelling at the ultrastructural level showed that alpha-SM actin expression in capillaries was exclusive to pericytes, and endothelial cells were negative. Compared to alpha-SM actin, non-muscle myosin was present in lower concentrations. By contrast, smooth muscle myosin isoforms, were absent. Pericytes were strongly positive for the intermediate filament protein vimentin, but lacked desmin which was consistently found in vascular smooth muscle cells. These results add support for a contractile role in pericytes of the CNS microvasculature, similar to that of vascular smooth muscle cells.

Actins↗

PubMed2001

Thyroid hormone receptor expression in rat placenta.

The expression of c- erbAalpha and -beta encoded thyroid hormone receptors (TR) was investigated in rat placenta between 16 and 21 days of gestation (dg), and in fetal liver and brain at 16 dg, using semi-quantitative RT-PCR and nuclear 3,5,3'-triiodothyronine (T(3)) binding. TRalpha1, TRbeta1, c- erbAalpha 2 and c- erbAalpha 3 mRNA abundance was unchanged in placenta between 16 and 21 dg, as was the dissociation constant (K(d)) of T(3) binding. The maximal T(3) binding capacity (B(max)) in placenta doubled over this period, suggesting placental TR binding activity is post-transcriptionally regulated. Transcript abundance in tissues at 16 dg can be summarized: TRalpha1, placenta=fetal liver fetal brain; c- erbAalpha 2 and alpha3, placenta=fetal liver<fetal brain; TRbeta2; none detected. T(3)binding in fetal liver and brain exhibited equivalent K(d) and B(max), the K(d) being less than 50 per cent of that in placenta, though B(max) was unchanged. The higher K(d)in placenta may reflect tissue-specific patterns of TR modification. In conclusion, rat placenta expresses significant levels of c- erbAalpha and -beta transcripts and protein, providing a possible mechanism of action for T(3) of maternal and fetal origin in this tissue.

Animals↗

PubMed2000

Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE.

Article abstract-Alpha synuclein, tau, synphilin, and APOE genotypes were analyzed in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and controls. The predisposing effect of the tau insertion polymorphism to the development of PSP is confirmed. However, no effect of alpha-synuclein, synphilin, or APOE variability on the development of PSP, or of tau, alpha-synuclein, APOE, or synphilin gene variability on the development of MSA, are demonstrated.

Apolipoproteins E↗

PubMed1995

Depletion of cortical cholecystokinin levels after excitotoxin injection into the nucleus basalis: sensitivity to MK-801.

The release of cholecystokinin (CCK) in vitro has been shown to be influenced by NMDA receptors. In this study we have investigated whether excitotoxin-induced seizure activity affects the release and tissue content of CCK. Excitotoxin injection caused a significant decrease in CCK in ipsilateral frontal, parietal and temporal cortex by (30-54%) at 8 h compared to contralateral cortex and sham-operated controls and the effect was reversed by 24 h. No change was detected in occipital cortex, hippocampus and nucleus accumbens. The effect in frontal and temporal cortex was maximal at 8 h and could be completely prevented by treatment with MK-801(3 mg/kg i.p.). Anaesthesia (pentobarbital) alone or in combination with MK-801 did not affect peptide levels at 8 h. CCK mRNA levels were also studied quantitatively by slot-blot analysis but were unaffected at 6, 8 and 24 h after excitotoxin injection. The decrease in CCK tissue levels indicated that seizure activity stimulated CCK release which was confirmed in ex vivo experiments where K(+)-evoked (34 mM) CCK release was significantly enhanced in ipsilateral cerebral cortex at 6 h compared to contralateral cortex.

Animals↗

PubMed1993

Abnormal glycine metabolism in motor neurone disease: studies on plasma and cerebrospinal fluid.

Plasma amino acid levels were measured following oral glycine loading in 43 patients with motor neurone disease (MND), eight normal subjects and 18 neurological disease controls with wasting or spasticity from a variety of other causes. Levels at baseline and 1.5 h after loading did not differ, but at 4 h, plasma glycine levels in MND patients remained significantly higher than in normal and neurological controls (P < 0.013). Cerebrospinal fluid glycine levels, which were maximal at 2.5 h, were also significantly higher in MND patients than neurological controls (P < 0.04). These observations suggest a defect of glycine 'housekeeping' in the central nervous system in MND which may be relevant to the pathogenesis of the disease.

Amino Acids↗

PubMed1991

Regulation of CCK release in cerebral cortex by N-methyl-D-aspartate receptors: sensitivity to APV, MK-801, kynurenate, magnesium and zinc ions.

Cholecystokinin octapeptide (CCK) is an abundant neuropeptide of cerebral cortex but its function in this region is largely unknown. In this study we have examined the effect of glutamate receptor activation on the depolarisation-induced release of CCK-like immunoreactivity from tissue slices of rat cerebral cortex. The K(+)-evoked release of cholecystokinin was found to be significantly increased by the three excitatory amino acid agonists effective against glutamate receptor subtypes. N-methyl-D-aspartate (NMDA), kainic acid and quisqualate. The facilitation of CCK release by NMDA was examined in more detail and shown to be significantly attenuated by Mg2+ (2.5 mM), Zn2+ (50 microM), MK-801 (0.1 and 0.3 microM), aminophosphonovaleric acid (100 microM) and kynurenic acid (100 microM and 300 microM). These results support the conclusion that release of CCK in cerebral cortex is modulated by the NMDA receptor.

2-Amino-5-phosphonovalerate↗

PubMed1990

Regional distribution of cholecystokinin messenger RNA in rat brain during development: quantitation and correlation with cholecystokinin immunoreactivity.

The regional distribution of CCK-octapeptide (CCK) and CCKmRNA were studied in parallel in rat brain during development in order to characterize changes in gene expression in different structures at different periods of development and to determine whether differential regulation of translation and peptide turnover occurs, by correlating peptide and mRNA levels. CCK was characterized by Northern blot analysis. Methods were developed for quantitation of CCKmRNA by in situ hybridization (ISH) and compared with results obtained by slot blot analysis. Analysis of CCKmRNA by ISH showed that CCKmRNA was abundant in cerebral cortex, hippocampus, dentate gyrus, thalamus, inferior colliculus and periaqueductal grey in keeping with the high concentrations of CCK-like immunoreactivity in cell bodies located in these regions. Quantitation of CCKmRNA by computerized densitometric image analysis by reference to [35S]brain paste standards gave a similar pattern to that obtained by slot blot analysis of regional RNA extracts. Distinctive patterns of CCK development were seen. In cerebral cortex and hippocampus, a marked increase in peptide and mRNA levels was found from day 1 which showed a steady increase up to adult levels. However, in the thalamus, the highest levels of mRNA and peptide were reached at a much earlier stage, generally by 14d. In contrast, inferior and superior colliculus showed a delayed onset of peptide expression.

Animals↗