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- Hedberg, MM, et al.
(author)
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Effect of huprine X on β-amyloid, synaptophysin and α7 neuronal nicotinic acetylcholine receptors in the brain of 3xTg-AD and APPswe transgenic mice
- 2010
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In: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 7:6, s. 379-388
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Journal article (peer-reviewed)abstract
- <i>Background:</i> Several studies implicate acetylcholinesterase (AChE) in the pathogenesis of Alzheimer’s disease (AD), raising the question of whether inhibitors of AChE also might act in a disease-modifying manner. Huprine X (HX), a reversible AChE inhibitor hybrid of tacrine and huperzine A, has shown to affect the amyloidogenic process in vitro<i>. </i>In this study, the aim was to investigate whether HX could affect the AD-related neuropathology in vivoin two mouse models. <i>Methods:</i>Tg2576 (K670M/N671L) (APPswe) and 3xTg-AD (K670M/N671L, PS1M146V, tauP301L) mice were treated with HX (0.12 µmol/kg, i.p., 21 days) or saline at 6–7 months. Human β-amyloid (Aβ) was measured by ELISA, synaptophysin by Western blot and α7 neuronal nicotinic acetylcholine receptors (nAChRs) were analyzed by [<sup>125</sup>I]α-bungarotoxin autoradiography. <i>Results:</i> Treatment with HX reduced insoluble Aβ1–40 (about 40%) in the hippocampus of 3xTg-AD mice, while showing no effect in APPswe mice. Additionally, HX markedly increased cortical synaptophysin levels (about 140%) and decreased (about 30%) the levels of α7 nAChRs in the caudate nucleus of 3xTg-AD mice, while increasing (about 10%) hippocampal α7 nAChRs in APPswe mice. <i>Conclusion:</i> The two mouse models react differently to HX treatment, possibly due to their differences in brain neuropathology. The modulation of Aβ and synaptophysin by HX in 3xTg-AD mice might be due to its suggested interaction with the peripheral anionic site on AChE, and/or via cholinergic mechanisms involving activation of cholinergic receptors. Our results provide further evidence that drugs targeting AChE affect some of the fundamental processes that contribute to neurodegeneration, but whether HX might act in a disease-modifying manner in AD patients remains to be proven.
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- Lithner, CU, et al.
(author)
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Pregnancy outcome for fetuses with increased nuchal translucency but normal karyotype
- 2016
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In: Journal of medical screening. - : SAGE Publications. - 1475-5793 .- 0969-1413. ; 23:1, s. 1-6
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Journal article (peer-reviewed)abstract
- To investigate pregnancy outcome for fetuses with nuchal translucency (NT) ≥3.5 mm but normal karyotype in the Stockholm (Sweden) area. Methods A retrospective population-based cohort study. From 2006 to 2012, fetal NT was measured in 55123 singleton pregnancies. There were 341 pregnancies with NT thickness ≥3.5 mm; 139 had a normal karyotype, 164 had an abnormal karyotype and 38 were removed from the study. Pregnancy outcome was defined as adverse (termination of pregnancy [TOP], miscarriage [MC], intrauterine fetal death [IUFD], or delivery of a child with structural defects or genetic disorders), or favourable (delivery of a child without any structural defects or genetic disorders diagnosed before discharge). Results Of the 139 high NT pregnancies with normal karyotype, 110 (79.2%) resulted in live births, one (0.7%) IUFD, 23 (16.5%) TOP and five (3.6%) MC. The risk of an adverse pregnancy outcome increased with increasing NT. Structural fetal defects were found in 28 (19.5%) of pregnancies undergoing second trimester ultrasound screening, of which seven resulted in live births and 21 were terminated. The most common structural defect was cardiac defects. Conclusions Adverse pregnancy outcome increased with increasing NT, even with normal karyotype, however, the prognosis is good if the second trimester ultrasound screening is normal.
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