INTERSTRAIN DIFFERENCES IN EMOTIONAL AND WEIGHT INDICES IN GC RATS WITH CATATONIC RESPONSE AND WISTAR RATS

In selecting rats for behavior, we observe a direct natural effect and affect the nonspecific stress function. In this process, new behavioral phenotypes appear in the strain under selection. They differ from the selected forms in the selection criterion. In the GC strain, a large proportion of the so-called nervous rats emerge. The criterion presumes the selection for the long cataleptic freezing character, whereas the nervous rats display elevated motor excitement: running, jumping, and vocalization. The main purpose of our study was to assess phenotypic indices in GC rats (abbreviated from genetic and catatonia) and recognize principal components of variability for emotional and weight indices. Rats of the ancestral Wistar population were taken as control. The following indices were measured: time of cataleptic freezing, excitement level, blood pressure, acoustic startle response, seizure activity, and weights of the heart, kidneys, adrenals, and spleen. Multivariate analysis methods were applied: factor analysis and principal component analysis. We confirmed the inclination of GC rats of the generation studied to freezing in quiet surrounding and after a strong acoustic sti - mulus. More pronounced startle responses, moderate hypertension, and larger weights of the heart and adrenals were noted. Two principal variability components were recognized: startle amplitude (PC1) and morphofunctional variability (PC2). The figure shows different locations of Wistar and GC individuals in principal component coordinates. The principal component method confirmed the genetic relationship between the startle and nervousness responses. It was shown that in PC2 the indices of heart, kidney, adrenal, and spleen weight exert negative effects, whereas the effects of startle and nervousness were positive. In the same component, an increase in the startle and nervousness responses positively correlates with the relative weights of the heart and adrenals. Differences in the directions of the contributions to the second component of morphofunctional variability are discussed.

SPERM QUALITY IN RATS PREDISPOSED TO THE MANIFESTATION OF CATATONIC REACTIONS

Catatonia is a psychopathological syndrome displayed as a motor disorder. Catatonia is a sign of many menthal disorders, particularly schizophrenia and depression, with a wide disrtibution in the human population. The GC (“genetic” and “catatonia”) rat strain was obtained from the Wistar rat strain by a long selection (78 generations) for the catatonic type of reaction and is a model of schizophrenic and depressive disorders in humans. It is known that selection for behavior including catatonic reactions results in neuroendocrine, reproductive and morphological changes in animals. However, the influence of selection for a catatonic reaction on the spermatogenic function of testes had not been studied. The aim of this study was to conduct a comparative investigation of sperm quality in rats of the GC and the Wistar strain. The epididymal sperm parameters (sperm count, sperm motility, sperm morphology) were measured, and body, testes and epididymal weight were determined at puberty (50 day of life) and at adulthood (90 day of life). The litter size of the GC and Wistar rats was determined. It was found that adult GC rats had a lower sperm count, sperm motility, testis weight, epydidymal weight and litter size compared to adult Wistar rats. However, at puberty, GC rats had a higher sperm count than the Wistar strain. Interstrain differences in sperm morphology were not found. It has been assumed that the changes of spermatogenic parameters in response to selection for catatonia are caused by changing the ontogenic pattern of testosterone secretion. In conclusion, the hereditary predisposition to catatonic reaction is associated with impaired sperm parameters in adult rats that reduces their chance to reproduction. The GC rat strain can be a perspective model for investigation of the relationship between the hereditary predisposition to catatonia and spermatogenesis

Epithelial Sodium Channel Is a Key Mediator of Growth Hormone-Induced Sodium Retention in Acromegaly

Acromegalic patients present with volume expansion and arterial hypertension, but the renal sites and molecular mechanisms of direct antinatriuretic action of GH remain unclear. Here, we show that acromegalic GC rats, which are chronically exposed to very high levels of GH, exhibited a decrease of furosemide-induced natriuresis and an increase of amiloride-stimulated natriuresis compared with controls. Enhanced Na+,K+-ATPase activity and altered proteolytic maturation of epithelial sodium channel (ENaC) subunits in the cortical collecting ducts (CCDs) of GC rats provided additional evidence for an increased sodium reabsorption in the late distal nephron under chronic GH excess. In vitro experiments on KC3AC1 cells, a murine CCD cell model, revealed the expression of functional GH receptors and IGF-I receptors coupled to activation of Janus kinase 2/signal transducer and activator of transcription 5, ERK, and AKT signaling pathways. That GH directly controls sodium reabsorption in CCD cells is supported by: 1) stimulation of transepithelial sodium transport inhibited by GH receptor antagonist pegvisomant; 2) induction of α-ENaC mRNA expression; and 3) identification of signal transducer and activator of transcription 5 binding to a response element located in the α-ENaC promoter, indicative of the transcriptional regulation of α-ENaC by GH. Our findings provide the first evidence that GH, in concert with IGF-I, stimulates ENaC-mediated sodium transport in the late distal nephron, accounting for the pathogenesis of sodium retention in acromegaly.