W Bloch

Publications (3)15.22 Total impact

• Article: Cellular expression of alpha7 nicotinic acetylcholine receptor protein in the temporal cortex in Alzheimer's and Parkinson's disease--a stereological approach.

  C Banerjee, J R Nyengaard, A Wevers, R A de Vos, E N Jansen Steur, J Lindstrom, K Pilz, S Nowacki, W Bloch, H Schröder
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  ABSTRACT: Cognitive deficits in Alzheimer's and Parkinson's disease are closely related to disturbed cholinergic transmission. The decrease of nicotinic acetylcholine receptor protein has been assessed by Western blotting and immunohistochemistry. Stereology, however, has not been used to assess numbers of receptor-expressing human cerebrocortical neurons. Our approach applies a combination of alpha7 subunit-immunohistochemistry with a stereological technique using defined stretches of pial surface as reference standard. The number of alpha7 subunit protein-expressing neurons in the Alzheimer temporal cortices amounted to approximately half of that of controls while numbers in Parkinson patients lay in between. No differences in the total number of neurons were seen. These results corroborate nonstereological studies on Alzheimer cortices and for the first time show a similar decrease in receptor expression in Parkinson's disease. They provide evidence that not only Alzheimer dementia but also cognitive deficits in Parkinson's disease may be related to decreased nicotinic receptor expression.
  Neurobiology of Disease 01/2001; 7(6 Pt B):666-72. · 5.40 Impact Factor
• Article: Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer's disease: histotopographical correlation with amyloid plaques and hyperphosphorylated-tau protein.

  A Wevers, L Monteggia, S Nowacki, W Bloch, U Schütz, J Lindstrom, E F Pereira, H Eisenberg, E Giacobini, R A de Vos, E N Steur, A Maelicke, E X Albuquerque, H Schröder
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  ABSTRACT: Impairment of cholinergic transmission and decreased numbers of nicotinic binding sites are well-known features accompanying the cognitive dysfunction seen in Alzheimer's disease (AD). In order to elucidate the underlying cause of this cholinoceptive dysfunction, the expression of two pharmacologically different nicotinic acetylcholine receptor (nAChR) subunits (alpha4, alpha7) was studied in the cerebral cortex of Alzheimer patients as compared to controls. Patch-clamp recordings of 14 dissociated neurons of control cortices showed responses suggesting the existence of alpha4- and alpha7-containing functional nAChRs in the human cortex. In cortices of Alzheimer patients and controls, the pattern of distribution and the number of alpha4 and alpha7 mRNA-expressing neurons were similar, whereas at the protein level a decrease in the density of alpha4- and alpha7-expressing neurons of approximately 30% was observed in Alzheimer patients. The histotopographical correlation of nAChR expression with accompanying pathological changes, e.g. accumulation of hyperphosphorylated-tau (HP-tau) protein and beta-amyloid showed that neurons in the vicinity of beta-amyloid plaques bore both nAChR transcripts. Neurons heavily labelled for HP-tau, however, expressed little or no alpha4 and alpha7 mRNA. These results point to an impaired synthesis of nAChRs on the protein level as a possible cause of the cholinoceptive deficit in AD. Further investigations need to elucidate whether interactions of HP-tau with nAChR mRNA, or alterations in the quality of alpha4 and alpha7 transcripts give rise to decreased protein expression at the level of individual neurons.
  European Journal of Neuroscience 08/1999; 11(7):2551-65. · 3.63 Impact Factor
• Article: Expression of alpha 4-1 and alpha 5 nicotinic cholinoceptor mRNA in the aging rat cerebral cortex.

  C Birtsch, A Wevers, J Traber, A Maelicke, W Bloch, H Schröder
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  ABSTRACT: Although important in neurodegeneration, systematic studies of nicotinic acetylcholine receptor expression in normal aging human brains are difficult to perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha 5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late middle aged), and 33-month-old (old) rats by nonisotopic in situ hybridization. In all groups transcripts were mainly present in layer II/III and V pyramidal neurons. The numerical densities of alpha 4-1 mRNA-containing neurons with respect to those of cresyl violet-stained neurons decreased with aging in the rat frontal and parietal cortex, while those of alpha 5 mRNA-containing neurons were not affected. These findings point to an age-related decrease of the percentages of numerical densities of alpha 4-1 mRNA-containing neurons, which has to be taken into account as a possible substrate for the well-known decrease of nicotine binding sites in the aging cerebral cortex.
  Neurobiology of Aging 18(3):335-42. · 6.19 Impact Factor