Differences in some properties of newborn and adult brain glutamate decarboxylase

Some properties of glutamate decarboxylase (EC 4.1.1.15) activity in brain of newborn and adult mouse were studied comparatively. It was found that glutamate decarboxylase of the newborn brain was strongly inactivated by homogenization in hypotonic medium, centrifugation of isotonic sucrose homogenates, preincubation at 37°C or the addition of Triton-X-100, whereas the adult brain enzyme was practically unaffected by any of these conditions. It was also found that the newborn glutamate decarboxylase was less activated by pyridoxal 5′-phosphate and less inhibited by pyridoxal 5′-phosphate oxime-O-acetic acid, than the adult enzyme. These differences do not exist for brain dihydroxyphenylalanine decarboxylase (EC 4.1.1.26) and are not due to the release of inhibitors from the newborn brain. On the basis of the results obtained it is postulated that two forms of glutamate decarboxylase exist in brain: a newborn form, which is unstable and has high affinity for pyridoxal 5′-phosphate, and an adult form, which is much more stable and has low affinity for pyridoxal 5′-phosphate. The possible implications of these findings in the establishment of the σ-aminobutyric acid dependent synaptic inhibitory mechanisms during development are discussed.     

TRH and TRH-OH in the pancreas of adult and newborn rats

TRH and its metabolite TRH-OH have been measured by specific radioimmunoassays in acid extracts of pancreas in adults and developing rats. TRH and TRH-OH immunoreactivity had the same ontogenic pattern with a maximal concentration on day 4 followed by a progressive return towards adult levels on day 20. A significant linear correlation was found between TRH levels and the TRH/TRH-OH ratio. The range of TRH/TRH-OH ratio varied from 136 +/- 1.6, at the peak of concentrations of both peptides, to 18 +/- 3.9 on day 20. Pancreatic TRH and TRH-OH had the same elution pattern as corresponding synthetic peptides both on Biogel P2 and high-pressure liquid chromatography. The origin of TRH-OH as well as its potential function need further investigations.     

Differences in some properties of newborn and adult brain glutamate decarboxylase.

Some properties of glutamate decarboxylase (EC 4.1.1.15) activity in brain of newborn and adult mouse were studied comparatively. It was found that glutamate decarboxylase of the newborn brain was strongly inactivated by homogenization in hypotonic medium, centrifugation of isotonic sucrose homogenates, preincubation at 37 degrees C or the addition of Triton-X-100, whereas the adult brain enzyme was practically unaffected by any of these conditions. It was also found that the newborn glutamate decarboxylase was less activated by pyridoxal 5'-phosphate and less inhibited by pyridoxal 5'-phosphate oxime-O-acetic acid, than the adult enzyme. These differences do not exist for brain dihydroxyphenylalanine decarboxylase (EC 4.1.1.26) and are not due to the release of inhibitors from the newborn brain. On the basis of the results obtained it is postulated that two forms of glutamate decarboxylase exist in brain: a newborn form, which is unstable and has high affinity for pyridoxal 5'-phosphate, and an adult form, which is much more stable and has low affinity for pyridoxal 5'-phosphate. The possible implications of these findings in the establishment of the gamma-aminobutyric acid dependent synaptic inhibitory mechanisms during development are discussed.     

Increase in tissue concentrations of histamine and 5-hydroxytryptamine following capsaicin treatment of newborn rats

Treatment of newborn rats with capsaicin is known to result in a permanent deficit of unmyelinated afferent neurones. The present study was concerned with the effect of neonatal capsaicin (50 mg kg^?1 s.c.) on tissue concentrations of histamine and 5-hydroxytryptamine (5-HT) in the adult rat. The amines were determined at the age of 5 to 6 months using high performance liquid chromatography. Histamine and 5-HT concentrations were significantly increased in the dorsal skin of the hind paw and the dorsal spinal cord. Histamine concentrations were also increased in lungs and ventral spinal cord while 5-HT concentrations were unaltered in these tissues. Both histamine and 5-HT concentrations were unchanged in the ventral skin of the hind paw, gastrointestinal tract and brain. It is proposed that the changes in the amine concentrations reflect a secondary response of histamine and 5-HT containing mast cells and neurones to the irreversible degeneration of unmyelinated afferent neurones caused by neonatal capsaicin treatment.     

Muscle regeneration induced by cells autografted in adult rats

Right triceps surae of 3-week-old Wistar rats were minced and devitalized with liquid nitrogen, a treatment which completely inhibits their ability to regenerate when they are orthotopically autografted. In a first series of experiments, cells were isolated from the left triceps surae, mixed with the devitalized right mince and autografted; in a second series, cells were moreover allowed to proliferate in vitro for a few weeks before being grafted. The regenerates were examined 60 days after surgery. In the first series, all the regenerates were contractile and developed a maximal isometric tetanic force of 18 +/- 6 mN (n = 5); they contained 152 +/- 80 muscle fibres located proximally, the number of which decreased along the proximo-distal axis, being 24 +/- 24 in the median part of the regenerate. The muscle fibres appeared histologically normal except for their shortness (less than 10 mm) and narrowness (mean luminal diameter: 30 microns). In the second series, 2 out of 5 regenerates were comparable with those of the first series except that their fibres were shorter; the 3 other regenerates were unexcitable. These experiments demonstrate that cells isolated from an adult striated muscle are able to regenerate striated muscle fibres in an adult animal and that these cells can retain this property if they are grown in culture.     

Triiodothyronine receptors in lymphocytes of newborn and adult rats.

Cytoplasmic and nuclear incorporation of 125I triiodothyronine by thymic lymphocytes has been demonstrated by electron microscopic autoradiography. Incorporation was significantly more pronounced in the newborn than in the adult age. The information emerging from the experime,tal observations contributes further evidence to the more precise interpretation of receptor maturation.     

Early hypoxic contracture of the myocardium in adult and newborn rats]

The effect of 30 min substrate free hypoxia (H) on isometric tension was studied in isolated myocardium (M) of adult (A) and newborn (N) rats. The perfusion with 50% Na+ H solution caused in AM the development of H contracture which was more than 50% higher than control contracture. H perfusion with 0.1 mM Ca2+, 1.0 mM La3+, and 10.0 mM of caffeine provides the discrimination of control and hypoNa+ contractures. It is assumed that early H contracture in AM is a result of inability of Ca-sequestering system to accumulate intracellular Ca2+ and Ca2+ influxing through the sarcolemma. In myocardium of N rats Na-Ca exchange is proposed as a main source of Ca2+ for H contracture development.     

Cold thermoregulatory changes induced by sleep deprivation in men

The aim of this study was to evaluate the thermoregulatory changes induced by 27-h of sleep deprivation (SD) in men at rest both in a comfortable ambient temperature and in cold air. A group of 12 male subjects were placed in a comfortable ambient temperature (dry bulb temperature,T _db = 25° C, relative humidity, rh = 40%–50% , clothing insulation = 1 clo) for 1 h and then they were submitted to a standard cold air test in a climatic chamber for 2h (T _db=1° C, rh = 40%–50%, wind speed = 0.8 m·s^–1, nude), before and after 27 h of sleep deprivation. Thermoregulatory changes (rectal temperature,T _re; mean skin temperature, _sk; metabolic heat production ) were monitored continuously. At comfortable ambient temperature, no significant change was observed after SD forT _re, _sk and . During the cold test,T _re did not change but _sk and were higher after SD (P<0.05). Increased (+ 6%,P < 0.05) was related to earlier and higher shivering, with a possible increase in the sensitivity of the thermoregulatory system as shown by the shorter time to onset of continous shivering (d): 8.66 (SEM 1.33) min versus 28.20 (SEM 1.33) min (P < 0.001) and by a higher _sk observed at d: 27.60 (SEM 1.40)° C versus 21.40 (SEM 0.60)° C (P < 0.001). These results were associated with higher cold sensations and shivering following SD. They also suggested that SD modified thermoregulatory responses at a central level especially in a cold environment.     

Ventricular remodeling induced by retinoic acid supplementation in adult rats

Retinoic acid (RA) plays a role in regulating cardiac geometry and function throughout life. The aim of this study was to analyze the cardiac effects of RA in adult rats. Wistar rats were randomly allocated to a control group (n = 18) receiving standard rat chow and a group treated with RA (n = 14) receiving standard rat chow supplemented with RA for 90 days. All animals were evaluated by echocardiography, isolated papillary muscle function, and morphological studies. Whereas the RA-treated group developed an increase in both left ventricular (LV) mass and LV end-diastolic diameter, the ratio of LV wall thickness to LV end-diastolic diameter remained unchanged when compared with the control group. In the isolated papillary muscle preparation, RA treatment decreased the time to peak developed tension and increased the maximum velocity of isometric relengthening, indicating that systolic and diastolic function was improved. Although RA treatment produced an increase in myocyte cross-sectional area, the myocardial collagen volume fraction was similar to controls. Thus our study demonstrates that small physiological doses of RA induce ventricular remodeling resembling compensated volume-overload hypertrophy in rats.     

Differential mechanisms of feeding modulation induced by amino sugars in rats

The present study examined and compared the effects of N-acetylglucosamine and 1-deoxy-N-acetylglucosamine on feeding behavior with those of glucosamine and 1-deoxyglucosamine. Infusion of 12 mu mole N-acetylglucosamine and 24 mu mole 1-deoxy-N-acetylglucosamine into the rat third cerebroventricle did not affect the feeding behavior. However, oral administration of 1200 mumol N-acetylglucosamine elicited feeding and 2400 mumol 1-deoxy-N-acetylglucosamine markedly suppressed feeding. These effects were abolished by truncal vagotomy. Both glucosamine and 1-deoxyglucosamine affected feeding by intra-third cerebroventricular and oral administration. These findings indicate that N-acetyl amino sugars modulate feeding behavior peripherally through the vagal afferent nerve.     

Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats

Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. ICV STZ is known to impair cholinergic neurotransmission by decreasing choline acetyltransferase (ChAT) levels, glucose and energy metabolism in brain and synthesis of acetyl CoA. However, no reports are available regarding the cholinesterase inhibitors in this model. In aging brain, reduced energy metabolism increases glutamate release, which is blocked by L-type calcium channel blockers. These calcium channel blockers have shown beneficial effects on learning and memory in various models of cognitive impairment. The present study was designed to investigate the influence of chronic administration of donepezil (cholinesterase inhibitor, 1 and 3 mg/kg) and lercanidipine (L-type calcium channel blocker, 0.3 and 1 mg/kg) on cognitive impairment in male Sprague-Dawley rats injected twice with ICV STZ (3 mg/kg) bilaterally on days 1 and 3. ICV STZ injected rats developed a severe deficit in learning and memory indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to control rats. Cholinesterase activity in brain was significantly increased in ICV STZ injected rats. Donepezil dose-dependently inhibited cholinesterase activity and improved performance in memory tests at both the doses. Lercanidipine (0.3 mg/kg) showed significant improvement in memory. When administered together, the effect of combination of these two drugs on memory and cholinesterase activity was higher than that obtained with either of the drugs when used alone.