| 1. |
|
|
| 2. |
|
|
| 3. |
- Blomqvist, Mia E-L, et al.
(författare)
-
Towards compendia of negative genetic association studies: an example for Alzheimer disease.
- 2006
-
Ingår i: Human genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 119:1-2, s. 29-37
-
Tidskriftsartikel (refereegranskat)abstract
- Most genetic sequence variants that contribute to variability in complex human traits will have small effects that are not readily detectable with population samples typically used in genetic association studies. A potentially valuable tool in the gene discovery process is meta-analysis of the accumulated published data, but in order to be valid these require a sample of studies representative of the true genetic effect and thus hypothetically should include some positive and an abundance of negative reports. A survey of the literature on association studies for Alzheimer disease (AD) from January 2004-April 2005, identified 138 studies, 86 of which reported positive findings other than for apolipoprotein E (APOE), strongly indicative of publication bias. We report here an analysis of 62 genetic markers, tested for association with AD risk as well as for possible effects upon quantitative indices of AD severity (mini-mental state examination scores, age-at-onset, and cerebrospinal fluid (CSF) beta-amyloid (Abeta) and CSF tau proteins). Within this set, only modest signals were present that, with the exception of APOE are easily lost when corrections for multiple hypotheses are applied. In isolation, results are thus broadly negative. Genes studied encompass both novel candidates as well as several recently claimed to be associated with AD (e.g. urokinase plasminogen activator (PLAU) and acetyl-coenzyme A acetyltransferase 1 (ACAT1)). By reporting these data we hope to encourage the publication of gene compendia to guide further studies and aid future meta-analyses aimed at resolving the involvement of genes in complex human traits.
|
|
| 4. |
- Brannvall, K, et al.
(författare)
-
19-Nortestosterone influences neural stem cell proliferation and neurogenesis in the rat brain
- 2005
-
Ingår i: European Journal of Neuroscience. - Uppsala Univ, Ctr Biomed, Dept Neurosci, Neurobiol Unit, S-75123 Uppsala, Sweden. Karolinska Inst, Sect Expt Geriat, KFC Novum, S-14186 Huddinge, Sweden. Minerva Med Res Inst, FIN-00290 Helsinki, Finland. : WILEY. - 0953-816X .- 1460-9568. ; 21:4, s. 871-878
-
Tidskriftsartikel (refereegranskat)abstract
- Abuse of androgenic anabolic steroids can affect brain function leading to behavioural changes. In this study, the effects of the testosterone analogue, 19-nortestosterone, on rat neural stem cells was examined. The androgen receptor is expressed by cultured embryonic and adult neural stem cells, and is also present in the ventricular epithelium during development and in the adult brain in, among others, dentate gyrus. In neural stem cells stimulated with epidermal growth factor, nandrolone reduced cell proliferation, especially in adult ones. The decrease was abolished by flutamide, a receptor antagonist. Nandrolone also decreased the BrdU labelling of neural stem cells in the dentate gyrus, demonstrating an effect of the hormone on cell proliferation in vivo. The effect of nandrolone was observed with both female and male rats but it was more pronounced in pregnant rats, indicating an involvement of oestrogen in nandrolone action. Nandrolone also decreased the number of newly born neuronal cells in the dentate gyrus of male rats. The results show that nandrolone has important effects on the proliferation and differentiation of neural stem cells expressing the cognate androgen receptor. The data show that the use of nandrolone may severely affect the formation of neural stem cells and could therefore have long-term negative consequences in the brain.
|
|
| 5. |
|
|
| 6. |
|
|
