Differential dominance of an allele of theDrosophila tßhgene challenges standard genetic techniques

The biogenic amine octopamine (OA) and its precursor tyramine (TA) are involved in controlling a plethora of different physiological and behavioral processes. The tyramine-ß-hydroxylase (tßh) gene encodes the enzyme catalyzing the last synthesis step from TA to OA. Here, we report differential dominance (from recessive to overdominant) of the putative nulltßhnM18allele in two behavioral measures in Buridan’s paradigm (walking speed and stripe deviation) and a proboscis extension assay in the fruit flyDrosophila melanogaster. The behavioral analysis of transgenictßhexpression experiments in mutant and wild type flies as well as of OA- and TA-receptor mutants revealed a complex interaction of both aminergic systems. Our analysis suggests that the different neuronal networks responsible for the three phenotypes show different sensitivity totßhgene dosage. This conclusion entails important implications for standard transgenic techniques, commonly used in functional genetics.

Brain alterations in depression

SUMMARYThis article describes a number of studies by our research group to find brain structures that may be involved in the symptoms of idiopathic depression, depression in Alzheimer's disease and depression in Parkinson's disease. Until recently, idiopathic depression has generally been related to deficiencies of aminergic systems. In Alzheimer patients we found a strong decrease in the number of neurons in the locus coeruleus and brain noradrenaline concentrations, but in depressed Alzheimer patients we did not find an extra de crease. This is in agreement with the finding that there is no cell loss in the locus coeruleus in idiopathic depression. We did find, however, that the number of corticotropin-releasing hormone-, vasopressin- and oxytocin expressing neurons, the number of corticotropin-releasing hormone neurons co-expressing vasopressin and the amount of corticotropin-releasing hormone -mRNA in idiopathic depression were strongly increased in the paraventricular nucleus of the hypothalamus. This result supports the hypothesis on the pathogenetic involvement of the hypothalamo-pituitary-adrenal axis in depression and is of clinical relevance, since it may provide a theoretical rationale for antidepressive therapy with CRH antagonists.