The expression profile of genes associated with behavior, stress, and adult neurogenesis along the hippocampal dorsoventral axis in tame and aggressive foxes.

The hippocampus plays the key role in stress response regulation, and stress response appears to be weakened in domesticated animals compared to their wild relatives. The hippocampus is functionally heterogeneous along its dorsoventral axis, with its ventral compartment being more closely involved in stress regulation. An earlier series of experiments was conducted with a unique breeding model of animal domestication, the farm silver fox (Vulpes vulpes), which included tame, aggressive, and unselected animals. A decrease in many indices of the hypothalamic-pituitary-adrenal activity was observed in tame animals. Also, adult hippocampal neurogenesis was more intense in tame foxes, and this fact may relate to reduced stress levels in this experimental population of foxes. Nevertheless, the molecular mechanisms responsible for the reduced stress response in tame animals remain obscure. In this study, serum cortisol levels and the mRNA levels of 13 genes in the dorsal and ventral hippocampus have been measured and compared in tame, aggressive, and unselected foxes. At the current stage of domestication, stress-induced cortisol levels in tame, aggressive, and unselected animals differ significantly from each other: tame foxes show the lowest levels, and aggressive ones, the highest. Twelve genes tested demonstrate significant gene expression differences between the dorsal and ventral hippocampi. These differences are mainly consistent with those found in rodents and humans. In tame foxes, significantly elevated mRNA levels were recorded for several genes: CYP26B1 for cytochrome P450 26B1 and ADRA1A for α1A adrenergic receptor in the dorsal hippocampus, whereas the level of NR3C2 mRNA for mineralocorticoid receptor was higher in the ventral. It is presumed that these genes constitute an important part of the mechanism reducing stress induced by contacts with humans and contribute to linking stress regulation with adult neurogenesis in tame foxes and domesticated animals in general.

[Increase in the concentration of sEH protein in renal medulla of ISIAH rats with inherited stress-induced arterial hypertension].

The concentration of soluble epoxide hydrolase (sEH) protein was studied in renal medulla of adult rats from hypertensive ISIAH strain and normotensive WAG strain. The sEH is a key enzyme in metabolism of epoxyeicosatrienoic acids capable of activating endothelial NO-synthase and nitrogen oxide formation, and therefore being vasodilators. An increase in the sEH protein concentration (that we found) allows one to assume that the oxidative stress is increased in the renal medulla of hypertensive rats, and the bloodflow is decreased.

[Expression of Catechol-O-Methyltransferase (Comt), Mineralocorticoid Receptor (Mlr), and Epithelial Sodium Channel (ENaC) Genes in Kidneys of Hypertensive ISIAH Rats at Rest and during Response to Stress].

Emotional stress plays a significant role in the processes of the development of arterial hypertension, especially in the presence of genetic predisposition. The origin and maintenance of hypertensive status during stress development can be activated by the sympathetic nervous system. An increase in sympathetic stimulation can, in turn, result in a change in the functions of kidneys, which provide fluid and electrolyte balance of the organism. A comparative study of the mRNA expression level of catechol-o-methyltransferase (Comt), mineralocorticoid receptor (Mlr), and ß-subunit of epithelial sodium channel (ß-ENaC) genes was conducted on the kidneys of hypertensive ISIAH rats and normotensive WAG rats at rest and after the effect of emotional stress. The discovered changes in the expression level of the selected genes confirm their involvement in increased sympathetic stimulation of the kidney, along with changes in the function of kidney regulation of fluid and electrolyte balance, which is an important factor of the development of sustained hypertension in the ISIAH rats strain.

[Renin-angiotensin system gene expression in the kidney and in the heart in hypertensive ISIAH rats].

The content of mRNA of renin-angiotensin system (RAS) genes in the kidney and heart of hypertensive ISIAH and normotensive WAG rats was measured by the real-time PCR. Statistically significant decrease of RAS gene mRNA was registered in the kidney of ISIAH rats, including Ren (by 45%), Ace (43%), AT1A (34%), COX-2 (50%). In the myocardium AT1A mRNA expression decreased by 28% while Ace mRNA expression increased by 80%. These results demonstrate the reduction of renal RAS basal activity in the hypertensive ISIAH rats, and this allows us to consider the ISIAH rat, as a low-renin hypertensive strain. In support of this viewpoint, in the ISIAH rats, a two-fold increase in the connective tissue sodium concentration as well as statistically significant plasma sodium increase (from 136 +/- 0,25 micromol/l in WAG to 139 +/- 0,3 micromol/l in the ISIAH rats) were found. Our conclusion backed by a tendency of the ISIAH plasma aldosterone level decrease giving in sum a classical picture of a low-renin hypertensive state in the ISIAH rats. It was suggested that the formation of low-renin arterial hypertension in the ISIAH rats may depend on changes in kidney ion channels function. In addition, renal NO system alterations could be also involved in the pathogenesis of arterial hypertension in the ISIAH rats.

Aldosterone and stress-dependent arterial hypertension.

Secretory activity of the adrenal cortex and hormonal reaction to emotional stress were examined in normotensive WAG and hypertensive ISIAH rats. Under nembutal narcosis (surgical stage), secretion of corticosteroid hormones and hormonal reaction to acute stress in hypertensive rats were enhanced. In these rats, the stress-induced elevation of aldosterone secretion was most pronounced, which indicates an important contribution of this hormone to the pathogenesis of stress-dependent arterial hypertension.