Stress and Depression: a Crucial Role of the Mineralocorticoid Receptor.

Cortisol and corticosterone act on the appraisal process, which comprises the selection of an appropriate coping style and the encoding of the experience for storage in the memory. This action exerted by the stress hormones is mediated by mineralocorticoid receptors (MRs), which are expressed abundantly in the limbic circuitry, particularly in the hippocampus. Limbic MR is down-regulated by chronic stress and during depression but induced by antidepressants. Increased MR activity inhibits hypothalamic-pituitary-adrenal axis activity, promotes slow wave sleep, reduces anxiety and switches circuit connectivity to support coping. Cortisol and emotion-cognition are affected by MR gene haplotypes based on rs5522 and rs2070951. Haplotype 1 (GA) moderates the effects of (early) life stressors, reproductive cycle and oral contraceptives. MR haplotype 2 (CA) is a gain of function variant that protects females against depression by association with an optimistic, resilient phenotype. Activation of MR therefore may offer a target for alleviating depression and cognitive dysfunction. Accordingly, the MR agonist fludrocortisone was found to enhance the efficacy of antidepressants and to improve memory and executive functions in young depressed patients. In conclusion, CORT coordinates via MR the networks underlying how an individual copes with stress, and this action is complemented by the widely distributed lower affinity glucocorticoid receptor (GR) involved in the subsequent management of stress adaptation. In this MR:GR regulation, the MR is an important target for promoting resilience.

Ketamine as antidepressant? Current state and future perspectives.

Major depressive disorder (MDD) is a serious mental disorder that ranks among the major causes of disease burden. Standard medical treatment targeting cerebral monoamines often provides only insufficient symptom relief and fails in approximately every fifth patient. The complexity of MDD therefore, reflects more than monoaminergic dysregulation. Initial research argues the case for excessive glutamate levels, suggesting that antiglutamatergic drugs might be useful in treating MDD. Ketamine is a non-selective, high-affinity N-methyl-D-aspartate receptor (NMDAR) antagonist most commonly used in pediatric and animal surgery. In the past, ketamine has gained popularity because of its ability to rapidly elevate mood, even in treatment-resistant and bipolar depression. However, there are still many obstacles before widespread clinical approval of ketamine treatment could become reality. In this review, ketamine's powerful antidepressant effects are discussed and further research necessary for therapeutic application is outlined. NMDAR antagonists provide an entirely new way of treating the manifold appearances of depression that should not be left unused.

The construction and cloning of synthetic genes coding for artificial proteins and expression studies to obtain fusion proteins.

Synthetic genes coding for artificial proteins with predefined and nutritionally valuable amino acid compositions have been constructed and cloned in bacterial plasmid vector pKK233-2. The genes were constructed from three easily interchangeable 'cassettes' encoding either essential, non-essential or branched-chain amino acid residues. A potential hairpin loop structure in the mRNA around the region of the ribosome binding site was probably the reason for blockage of translation from this vector. Two selected genes, AHB (containing one copy of each cassette) and A6 (consisting of six copies concatemerized A cassette) were cloned into pUR300, a beta-Gal fusion vector and expressed as fusion proteins beta-Gal-AHB and beta-Gal-A6.