Scopolamine Administration Modulates Muscarinic, Nicotinic and NMDA Receptor Systems

Studies on the effect of scopolamine on memory are abundant but so far only regulation of the muscarinic receptor (M1) has been reported. We hypothesized that levels of other cholinergic brain receptors as the nicotinic receptors and the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory formation, would be modified by scopolamine administration

Western blot results of Nic 7.

<p>Nic7 complex levels were significantly higher in scopolamine-treated groups. Significant differences were also observed when scopolamine-treated trained and untrained mice were compared.</p

Western blot results of Nic 4.

<p>Although a trend was suggested no significant differences between groups were observed.</p

Western blot results of NR1.

<p>NR1 containing NMDA complex levels (band 1) were significantly increased in the scopolamine-treated trained group vs the vehicle-treated and trained panel (A). Band 2 (B) was not significantly different between groups.</p

Loading control.

<p>The membrane used for immunoblotting was stained by Coomassie blue R-350. Adaequate loading was shown.</p

Western blot results of M1.

<p>The M1 receptor complex levels were significantly higher in scopolamine-treated groups.</p

Scheme of multiple T-maze.

<p>The multiple T-maze is a landmaze paradigm testing spatial memory. Animals with food deprivation search for food that is provided in the goal box.</p

Results in the Rota rod.

<p>Significant differences in rota rod performance, in scopolamine-treated vs vehicle-treated groups (P≤0.05) are shown. Numbers are representing seconds of remaining on the revolving rod.</p

Activins and activin antagonists in hepatocellular carcinoma

In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β (TGFβ) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo- or heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis