Two genetic rat models of arterial hypertension show different mechanisms by which adult hippocampal neurogenesis is increased.

To investigate strain differences and genetic effects on different aspects of neurogenesis, we compared young adult spontaneously hypertensive/hyperactive rats (SHR) and stroke-prone SHR (SHRSP) with the genetic control WKY strain. In both hypertensive/hyperactive strains, the number of newly generated neurons and the number of lineage-determined cells as detected by doublecortin (DCX) immunoreactivity were significantly increased. SHRSP had significantly more DCX-positive cells than the other groups.

Progress in the identification of stroke-related genes: emerging new possibilities to develop concepts in stroke therapy.

Stroke is a very complex disease influenced by many risk factors: genetic, environmental and comorbidities, such as hypertension, diabetes mellitus, obesity and having had a previous stroke. Neuroprotective therapies that have been found to be successful in laboratory animals have failed to produce the same benefits in clinical trials. Currently, a re-analysis of the clinical trial failures is underway and new therapeutic approaches using the growing knowledge from neurogenesis and neuroinflammation studies, combined with the information from gene expression studies, are taking place.

Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats.

Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains unknown. To determine if the increased cardiac ACE1 actively plays a role or is merely the consequence of pathological changes in the process of cardiac hypertrophy, we generated a transgenic rat model with selective over-expression of human ACE1 in the cardiac ventricles.

alpha-Tropomyosin mutations Asp(175)Asn and Glu(180)Gly affect cardiac function in transgenic rats in different ways.

To study the mechanisms by which missense mutations in alpha-tropomyosin cause familial hypertrophic cardiomyopathy, we generated transgenic rats overexpressing alpha-tropomyosin with one of two disease-causing mutations, Asp(175)Asn or Glu(180)Gly, and analyzed phenotypic changes at molecular, morphological, and physiological levels. The transgenic proteins were stably integrated into the sarcomere, as shown by immunohistochemistry using a human-specific anti-alpha-tropomyosin antibody, ARG1. In transgenic rats with either alpha-tropomyosin mutation, molecular markers of cardiac hypertrophy were induced.