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In order to explore the morphological basis of the altered feeding behaviour of old rats, an ultrastructural investigation of the magnocellular neurons of the hypothalamic paraventricular nucleus (PVN) was performed. Young and old male Wistar rats, 5 and 24 months old, respectively, and with each age group comprising 12 animals, were divided into 3 groups. The rats in Group I were used as controls (normally fed), the rats of Group II were fasted for 48 hours and in Group III the rats were fasted for 48 hours and then refed for 24 hours. The brains were fixed by perfusion and histological and ultrathin sections were obtained by routine methods. Common features of the magnocellular PVN neurons of young and old rats were abundant Golgi complexes and short fragments of RER localised at the cell periphery. In contrast to young rats, the PVN neurons of old animals showed deep indentations of the nuclear envelope and agerelated residual bodies. In both age groups fasting for 48 hours led to the expansion of the Golgi complexes and dilatation of RER cisternae. In contrast to those in fed rats, RER cisternae in the neurons of old fasted animals were situated between the nuclear envelope and the Golgi zone. Prolonged RER cisternae were distributed in the peripheral cytoplasm of refed old rats. Our observations suggest that at the ultrastructural level the process of ageing does not change the responsiveness of magnocellular PVN neurons to fasting-refeeding.
Galactosamine (GalN), a well-known hepatotoxin that depletes the cellular pool of uracil nucleotides, was previously shown to have greater impact on the inhibition of protein synthesis in hepatocytes of old rats as compared with young animals (Kmiec 1994, Ann. N.Y. Ac. Sci. 717, 216-225). In the present study we compared the effects of GalN on the nucleotide content (measured by ion-exchange HPLC) in the livers of young (4 months), adult (12 months), and old (24-26 months old) rats two hours after its intraperitoneal administration. UTP content of the livers of old control rats was significantly lower (by 28%) than that of young animals. GalN administration decreased the UTP content in the livers of young, adult and old rats by, respectively, 55%, 65% and 89%, and increased the content of UDP-sugars by 189%, 175% and 305%. The hepatic content of ATP, ADP, AMP, NAD, GTP except CTP did not differ significantly among the age groups of rats studied, and was not changed by GalN treatment. The content of CTP was significantly higher in old rats (P < 0.03) upon GalN treatment. The lower hepatic content of UTP may partially explain the increased sensitivity of hepatocytes and livers of old rats to the action of galactosamine, and pos­sibly to other hepatotoxic compounds that decrease transcription in the liver.
This study was conducted to assess the effect of the leucine metabolite, 3-hydroxy-3-methylbutyrate (HMB) on animal performance, and also cathepsins and calpain II activities in the gastrocnemius muscle in young rats undergoing dexamethasone (DX) treatment and subsequent recovery. Five days of DX administration resulted in an increase in calpain activity. During 5 days of recovery alone, calpain activity was still elevated whereas HMB treatment decreased calpain activity to the values observed in the control group. DX treatment increased the total lysosomal proteolytic activity. HMB administration during the recovery period accelerated return of the proteolytic enzymes activity to the control values. The use of selective inhibitors of thiol and aspartic cathepsins (leupeptin and pepstatin, respectively) allowed us to determine the type of cathepsin responsible for the DX-induced proteolysis observed. Since DX treatment decreased cathepsin D activity (which returned to the control values during recovery) it is assumed that thiol cathepsins are involved in the increase of lysosomal proteolysis observed. We have demonstrated that lysosomal and Ca+2-dependent proteinases involved in myofibryllar protein degradation differ in their activity due to DX treatment. It has been concluded that HMB modifies muscle proteolysis through changes in the activity of the proteolytic enzymes. Practical applications of this phenomenon are discussed.
Many hypothalamic nuclei are involved in the regulation of food intake and energy homeostasis. An ultrastructural investigation of the hypothalamic ventromedial nucleus (VMN), a hypothetical “satiety centre” was performed to explore the morphological basis of altered feeding behaviour of old rats in an experimental model of fasting/refeeding. Young (5 months old, n = 12) and old (24 months old, n = 12) male Wistar rats were fasted for 48 hours, then refed for 24 hours and sampled thereafter. Brain tissue was fixed by perfusion, histological and ultrathin sections were obtained by routine methods. Although food intake was similar in control young and old rats, during refeeding old animals consumed less chow than young ones. The EM analysis of VMN neurones of old control rats revealed, besides typical age-related residual bodies, deep indentations of the nuclear envelope and the presence of long, undulating rough endoplasmic reticulum cisternae in the cell periphery. In both young and old rats fasting for 48 hours led to the expansion of Golgi complexes and increased folds of the nuclear envelope, which is suggestive of enhanced cellular activity of the VMN neurones. These fasting-induced alterations were sustained in the VMN neurones of refed rats in both age groups. The results showed that the VMN neurones of old control rats differ at the ultrastructural level from young ones. However, starvation and subsequent refeeding cause similar alterations in the hypothalamic neurones of “satiety centre” of both young and old rats.
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