Nonneuronal cholinergic system in human erythrocytes : biological role and cinical relevance

The original publication is available at www.springerlink.com© Springer Science+Business Media, LLC 2010Acetylcholine is well known in the medical setting as one of the most exemplary neurotransmitters. Its ubiquity in nature otherwise suggests a theoretically diverse spectrum of action and an extremely early appearance in the evolutionary process. In humans, acetylcholine and its synthesizing enzyme, choline acetyltransferase, have been found in various nonneural tissues such as the epithelium, mesothelium, endothelium, muscle, immune cells and blood cells. The widespread expression of nonneuronal acetylcholine is accompanied by the ubiquitous presence of acetylcholinesterase and nicotinic/muscarinic receptors. Structural and functional dissimilarities are evident between the nonneuronal and neuronal cholinergic systems. An increasing body of evidence throughout the last few years has placed acetylcholine as a major cellular signaling molecule in many pathways. Furthermore, numerous erythrocyte physiological events in the microcirculation are strongly regulated by acetylcholine. Thus, it is time to revise our understanding of the role of vascular acetylcholine in humans. Its biological and pathobiological roles must be evaluated in more detail to eventually achieve novel therapeutical targets. The present article reviews recent findings about nonneuronal acetylcholine in red blood cells, with special regard to (1) red cell rheology, (2) plasma ion concentrations, (3) nitric oxide intracellular translocation and metabolism and (4) band 3 protein phosphorylation

The loudness dependence of auditory evoked potentials (LDAEP) as an indicator of serotonergic dysfunction in patients with predominant schizophrenic negative symptoms

Besides the influence of dopaminergic neurotransmission on negative symptoms in schizophrenia, there is evidence that alterations of serotonin (5-HT) system functioning also play a crucial role in the pathophysiology of these disabling symptoms. From post mortem and genetic studies on patients with negative symptoms a 5-HT dysfunction is documented. In addition atypical neuroleptics and some antidepressants improve negative symptoms via serotonergic action. So far no research has been done to directly clarify the association between the serotonergic functioning and the extent of negative symptoms. Therefore, we examined the status of brain 5-HT level in negative symptoms in schizophrenia by means of the loudness dependence of auditory evoked potentials (LDAEP). The LDAEP provides a well established and non-invasive in vivo marker of the central 5-HT activity. We investigated 13 patients with schizophrenia with predominant negative symptoms treated with atypical neuroleptics and 13 healthy age and gender matched controls with a 32-channel EEG. The LDAEP of the N1/P2 component was evaluated by dipole source analysis and single electrode estimation at Cz. Psychopathological parameters, nicotine use and medication were assessed to control for additional influencing factors. Schizophrenic patients showed significantly higher LDAEP in both hemispheres than controls. Furthermore, the LDAEP in the right hemisphere in patients was related to higher scores in scales assessing negative symptoms. A relationship with positive symptoms was not found. These data might suggest a diminished central serotonergic neurotransmission in patients with predominant negative symptoms