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Thomas Arendt

Publications and source records attributed to Thomas Arendt.

63 records · Page 4Linked to original sources
PubMed2002

The role of tissue transglutaminase (transglutaminase type II) for the intestinal manifestations of murine semi-allogenic graft-versus-host disease.

The intestinal manifestation of acute murine semi-allogenic graft-versus-host (GvH) disease is characterized by the occurrence of lymphocytic infiltrates in the lamina propria, by crypt hyperplasia and villous atrophy. In a histological respect, this animal model resembles human celiac disease. Tissue transglutaminase (tTG) (transglutaminase type II) has been identified to be the major B cell autoantigen in celiac disease. Furthermore, tissue transglutaminase has been implicated to be involved in its pathogenesis. Therefore, we aimed to investigate whether tissue transglutaminase is expressed in the intestines of GvH animals and whether its inhibition has any effect on the intestinal histology. Sera of patients with celiac disease and anti-tTG antibodies were purified. These antibodies were used for immuno-histochemistry of jejunal cryosection from GvH and syngenic control animals at day 6 after lymphocyte transfer. Furthermore, GvH mice were treated with antitTG antibodies and with the inhibitor of tissue transglutaminase monodansyl-cadaverine. The effect of this treatment on the development of crypt hyperplasia and villous atrophy were examined by light microscopy of hematoxylin-eosin (H&E) stained jejunal paraffin sections. We found a strong subepithelial expression of tissue transglutaminase in GvH animals but not in syngenic control mice. The localization of tTG seemed to be associated with the extracellular matrix (ECM). However, neither the treatment of GvH animals with anti-tTG antibodies nor the application of mono-dansyl-cadaverine prevented the development of crypt hyperplasia and villous atrophy. Similar to the situation in human celiac disease tissue, transglutaminase is highly expressed in the intestine of animals undergoing a semi-allogenic graft-versus-host reaction. However, this enzyme is probably not involved in the development of crypt hyperplasia and villous atrophy in this animal model.

Animals↗
PubMed2002

Immunocytochemical evidence for the striatal nature of the rat lateral part of interstitial nucleus of the posterior limb of the anterior commissure (IPAC).

The present study focuses on the basal forebrain region originally designated as fundus striati, but currently known as 'interstitial nucleus of the posterior limb of the anterior commissure' (IPAC). Using multiple immunofluorescence of the calcium-binding proteins parvalbumin and calbindin, the GABA(A) receptor alpha1-subunit, vasoactive intestinal polypeptide (VIP), met(5)-enkephalin (MENK) and glutamic acid decarboxylase (GAD), it was shown that VIP-immunostained axons, which are typical for major parts of the extended amygdala, densely innervate only the medial part of IPAC, while they are absent in the lateral part. On the other hand, large-sized GABAergic, parvalbumin- and GABA(A) receptor alpha1-subunit-immunoreactive neurons, which are densely covered by separate GAD- and MENK-immuno reactive terminals and a type of medium-sized alpha1-subunit-monolabelled cells, occur in the dorsal striatum and in the adjacent lateral part of IPAC as well. Large-sized neurons double labelled for parvalbumin and the GABA(A) receptor alpha1-subunit are also widely distributed in the neighbouring ventral pallidum. Neurons of this type are absent, however, in the medial part of IPAC and other extended amygdala subunits. Our findings confirm the recent suggestion of a morphofunctional dichotomy of IPAC (Comp. Neurol. 439 (2001) 104), as only the medial part reveals characteristics as typical for extended amygdala, while its lateral part exhibits cytochemical peculiarities of striatal tissue. Therefore, the term 'lateral part of IPAC' should be replaced by the term 'putaminal fundus (fundus putaminis)' according to recently published designations of corresponding striatal constituents (Atlas of the Human Brain, 2002, Academic Press, San Diego, CA; J. Chem. Neuroanat. 23 (2002) 75).

Animals↗
PubMed2002

Dephosphorylation of tau protein by calcineurin triturated into neural living cells.

Alzheimer disease and related dementia are characterized by the presence of hyperphosphorylated tau aggregated into filaments. The role of tau phosphorylation in the fibrillogenesis has not yet been unraveled. Therefore, it is important to know which phosphatases can dephosphorylate tau protein in vivo. The effect of recombinant purified calcineurin (CN(PP2B)) and several calcineurin mutants on tau phosphorylation was studied in two neuronal like cell lines PC12 and SH-SY5Y. The modulation of tau phosphorylation at Serl99/Ser202, Ser396/Ser404, Ser262/Ser356, and Thr181 sites was examined in these cell lines using the phosphorylation state-dependent antitau antibodies Tau 1, PHF1, 12E8, and AT270. The results have shown that CN directly dephosphorylates all of those sites of tau protein. Recombinant calcineurin introduced into cells that have previously been treated with okadaic acid and cyclosporin A, which are inhibitors of phosphatases (PP1/PP2A and PP2B), has a direct effect on the phosphorylation status on all phosphorylation sites studied. We conclude that calcineurin is (besides PP2A) a important modulator of tau phosphorylation in vivo.

Animals↗
PubMed2002

Cyclin D1 and cyclin E are co-localized with cyclo-oxygenase 2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex.

Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) seems to reduce the progression of several diseases, including colon cancer, lung cancer, breast cancer and Alzheimer disease (AD). Several studies have shown that NSAIDs can modulate cell cycle progression, especially in the G0/G1 phase. The main target of most NSAIDs is the enzyme cyclo-oxygenase (COX), which occurs in 2 isoforms, COX-1 and COX-2. In AD and non-demented control brain, COX-2 is expressed in neuronal cells. In this study the expression of COX-2, cyclin D1, and cyclin E was investigated at the immunohistochemical level in AD and non-demented control temporal cortex. COX-2, cyclin D1, and cyclin E expression was detected in pyramidal neurons in both AD and control patients. The number of COX-2-immunoreactive neurons positively correlated with the number of cyclin E- and cyclin D1-immunoreactive neurons. Moreover, immunostaining of sequential tissue sections and double immunofluorescence labeling revealed co-expression of COX-2 and cyclin D1 and E in neuronal cells. In addition, an inverse correlation was observed between the neuronal expression of COX-2 and cyclin E and the Braak score for amyloid beta deposits. Our findings suggest a relationship between the neuronal expression of COX-2 and cell cycle markers, which may be involved early in AD pathology.

Aged↗
PubMed2002

AbetaPP induces cdk5-dependent tau hyperphosphorylation in transgenic mice Tg2576.

Previous studies of Abeta-induced neuronal damage of hippocampal cells in culture have provided strong evidence that deregulation of the Cdk5/p35 kinase system is involved in the neurodegeneration pathway. Cdk5 inhibitors and antisense probes neuroprotected hippocampal cells against the neurotoxic action of Abeta. To further investigate the mechanisms underlying the participation of Cdk5 in neuronal degeneration, the transgenic mouse containing the Swedish mutations, Tg2576, was used as an animal model. Immunocytochemical studies using anti-Abeta(1-17) antibody evidenced the presence of labeled small-clustered core plaques in the hippocampus and cortex of 18-month-old transgenic mice brains. The loss of granular cells without a compressed appearance was detected in the vicinity of the cores in the dentate gyrus of the hippocampus. Immunostaining of Tg2576 brain sections with antibodies AT8, PHF1 and GFAP labeled punctuate dystrophic neurites in and around the amyloid core. Reactive astrogliosis around the plaques in the hippocampus was also observed. Studies at the molecular level showed differences in the expression of the truncated Cdk5 activator p25 in the transgenic animal, as compared with wild type controls. However no differences in Cdk5 levels were detected, thus corroborating previous cellular findings. Interestingly, hyperphosphorylated tau epitopes were substantially increased as assessed with the AT8 and PHF1 antibodies, in agreement with the observation of a p25 increase in the transgenic animal. These observations strongly suggest that the increased exposure of Alzheimer's type tau phosphoepitopes in the transgenic mice correlated with deregulation of Cdk5 leading to an increase in p25 levels. These studies also provide further evidence on the links between extraneuronal amyloid deposition and tau pathology.

Alzheimer Disease↗
PubMedDate not supplied

Cyclin C expression is involved in the pathogenesis of Alzheimer's disease.

The expression of different cell cycle proteins in terminally differentiated neurons apparently precedes cell death or contributes to pathogenetic progression of Alzheimer's disease (AD). Cyclins and cyclin-dependent kinases (Cdks), physiologically involved in mitotic processes of proliferating cells, are elevated in neurons prone to dedifferentiation and degeneration. Previously, it was shown that even inhibitors of the Cdks as p16(INK4a), p18(INK4c) or p27(KIP1) are expressed in neurons of AD patients, indicating a rather complete involvement of cell cycle machinery in affected neurons. The aim of this study was to examine the involvement of the non-classical cyclin C in the pathogenetic process of AD. A marked elevated immunoreactivity of cyclin C was found both in neurons and astrocytes in AD. Increased levels of cyclin C RNA were detected by ribonuclease protection assay (RPA) in severe AD cases. Colocalization of cyclin C and its preferred binding partner, Cdk8, was only observed in astrocytes but not in neurons. The present observations suggest different cellular functions of cyclin C in neurons and astrocytes in AD.

Aged↗
PubMedDate not supplied

Theta-power differences in patients with mild cognitive impairment under rest condition and during haptic tasks.

The aim of this study was to investigate spectral EEG theta-power during perceptive-cognitive demands in age-homogeneous groups of subjects with mild cognitive impairment (MCI), mild dementia (MDE), and a healthy control (CO) group. The present study includes 51 subjects (23 males, 28 females). We used the scales of the CDR (clinical dementia rating) to assign the subjects to the different groups. EEG data were collected during 10 minutes rest condition with eyes closed and during haptic perception test. The quality of the haptic reproductions differed significantly between CO and MCI, as well as between CO and MDE. The statistical comparison between EEG theta-power under rest condition and theta-power during haptic tasks revealed a significant decrease in theta-power during haptic tasks in all three groups over parieto-occipital regions. During haptic tasks, the theta-power was significantly different between CO and MDE over occipital regions and over parieto-temporal regions. A significant difference between CO and MCI was only revealed over right occipital regions (O2). Spectral theta-power during haptic tasks is a suitable measure to distinguish healthy subjects (CO) from patients with MCI respectively MDE. The results show that haptic tasks are sensitive to early perceptive-cognitive and functional deficits in patients with MCI.

Aged↗