Finerenone: Efficacy of a New Nonsteroidal Mineralocorticoid Receptor Antagonist in Treatment of Patients With Chronic Kidney Disease and Type 2 Diabetes.

Mineralocorticoid receptor stimulation by aldosterone can cause various cardiovascular and renal disease complications. Finerenone is a new oral nonsteroidal mineralocorticoid receptor antagonist that has been approved for clinical use by the Federal Drug Aministration, and has been shown in clinical trials to reduce the risk of sustained estimated glomerular filtration rate decline, end-stage renal disease, nonfatal myocardial infarction, hospitalization for heart failure and cardiovascular death in adult patients with chronic kidney disease associated with type 2 diabetes. The drug has also been shown to have fewer side effects than the steroidal mineralocorticoid receptor antagonists like spironolactone and eplerenone.

Serotonin receptor 4 in the hippocampus modulates mood and anxiety.

Serotonin receptor 4 (5-HTR) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5-HTR is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5-HTR knockout mouse line to dissect the function of 5-HTR in specific brain regions and cell types.

Decreasing Striatopallidal Pathway Function Enhances Motivation by Energizing the Initiation of Goal-Directed Action.

Unlabelled: Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of the striatopallidal "no-go" pathway. To this end, we expressed the Gαi-coupled designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N-oxide (CNO).

Behavioral phenotyping of minipigs transgenic for the Huntington gene.

Background: While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies.

Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments.

Background: As novel treatment approaches for Huntington's disease (HD) evolve, the use of transgenic (tg) large animal models has been considered for preclinical safety and efficacy assessments. It is hoped that large animal models may provide higher reliability in translating preclinical findings to humans, e.g.

FDG μPET Fails to Detect a Disease-Specific Phenotype in Rats Transgenic for Huntington's Disease – A 15 Months Follow-up Study.

Background: FDG-PET detects hypometabolism in premanifest and symptomatic Huntington's disease (HD). A cross-sectional study suggested that whole-brain FDG-PET is capable to detect a phenotype in transgenic (tg) HD rats. Recently, a longitudinal follow-up study showed no FDG-PET changes in tgHD rats.