Weanling Rats Research Articles

Cysteine Supplementation and Reduction of Total Parenteral Nutrition—Induced Hepatic Lipid Accumulation in the Weanling Rat

Total parenteral nutrition (TPN)-induced hepatic steatosis is the most common complication of TPN administration to humans. The mechanism of TPN-induced hepatic steatosis has not been studied in young mammals. The goal of this study was to determine the mechanism of TPN-induced hepatic steatosis in the weanling rat and the effect of supplementation of TPN with choline and/or cysteine on TPN-induced hepatic steatosis. In the weanling rat, we investigated the effect of TPN administration on histologic hepatic steatosis, total hepatic lipid, hepatic acetyl-CoA-carboxylase (ACC--the rate limiting enzyme in fatty acid synthesis) specific activity, and total plasma lipids. TPN administration resulted in a threefold increase in hepatic lipid as compared with control and sham animals (TPN 138 +/- 12 mg/g liver versus control 57 +/- 1), an increase in histologic steatosis (TPN 3.7 versus control 1.3), and a decline in total plasma lipid (TPN 2.1 +/- 0.3 g/L versus control 4.1 +/- 0.3). TPN-induced hepatic steatosis in the weanling rat was not associated with an increase in ACC specific activity (TPN 2.10 +/- 0.33 nmol/min/mg protein versus control 2.85 +/- 0.23). Supplementation of the TPN with choline (15 mg/day) did not significantly lessen hepatic steatosis; however, supplementation of TPN with cysteine (2.5 mg/day) or with cysteine and choline did result in a significant lessening of hepatic lipid content and of histologic steatosis and a normalization of total plasma lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effect of coconut oil on renal necrosis occurring in rats fed a methyl-deficient diet.

Weanling rats fed a methyl-deficient diet develop renal necrosis with acute renal failure. The aim of this experiment was to explore further the role of coconut oil in this experimental model. Weanling Wistar male rats were fed methyl-deficient and their controls were fed methyl-supplemented diets. Coconut oil was fed at 14% and 20%, the latter concentration with and without 1% safflower oil (rich in linoleic acid); other groups received similar diets but instead of coconut oil, a mixture of hydrogenated vegetable oil and corn oil (rich in unsaturated fatty acids) was employed. Coconut oil fed at a 14% concentration did not evidence any protective outcome in relation to the renal lesions. Coconut oil at a 20% concentration showed a protective effect, mainly when the diet included safflower oil. The renal protective effect was evidenced by less or no mortality and increased survival time in the methyl-deficient rats receiving coconut oil, as well as by a reduced incidence (%) and severity of the renal lesions as evaluated by renal weight, and type (tubular and cortical necrosis or repair) and extent (grade) of the renal damage. The lack of a protective outcome when coconut oil was fed at 14%, along with the fact that in those rats receiving coconut oil at 20% the protection was greater when the diet was supplemented with 1% safflower oil, indicates that the protective effect should be attributed to the type of fatty acids coconut oil has and not to their shortage of essential fatty acids.

Thallium distribution in organs and brain regions of developing rats

The concentration of thallium in body organs and brain regions was studied in rats as a function of the animals age from newborn to 20-days old. Thallium was analyzed at different times after a single sublethal i.p. injection of the metal (16 mg/kg). The results indicate that the brain is less permeable to thallium in the older animals, suggesting that reduced thallium transport into the brain is related to the establishment of the blood-brain barrier in the rats. Differences between weanling and newborn rats were also found in regard to regional distribution of thallium in the brain as the older animals showed a region-dependent distribution while newborn rats presented an homogeneous content of thallium among all regions.

Neogenesis of Skeletal Muscle in the Postinflammatory Rat Peritoneum

During the healing phase of a chemical peritonitis, one or several skeletal muscle fibers develop, de novo, in the peritoneum of the adult or weanling rat diaphragm. One week after the initial injury the new muscle fibers are narrow and have central nuclei and cross-striations. The fibers increase progressively in caliber and the nuclei take up a subsarcolemmal location. The newly formed muscle fibers are separated from the intrinsic diaphragmatic muscle by an elastic membrane and by a band of hyaline connective tissue. They are separated from the peritoneal surface by a zone of granulation tissue. Most new fibers are oriented at right angles to the intrinsic diaphragmatic muscle fibers. Their location and orientation suggest an origin from mesothelium or from fibroblasts in the granulation tissue rather than from the intrinsic diaphragmatic muscle. A similar phenomenon can be induced in the pleura on the other side of the diaphragm. In contrast, damage to the diaphragmatic muscle by injection of aluminum lactate does not engender myogenesis in the location described despite active regeneration in the intrinsic muscle.

Paradoxical autonomic responses to aversive stimuli in the developing rat.

The goals of this research were to determine (a) the change in heart rate elicited by aversive auditory stimuli in the laboratory rat at different ages and (b) the autonomic origins of those changes at each age. The results of the first 2 experiments showed that aversive white noise stimuli elicited cardiac deceleration in preweanling (16-day-old) rats and cardiac acceleration in weanling (23-day-old), periadolescent (30-day-old), and adult (60-day-old) rats. Subsequent experiments showed that (a) the decrease in heart rate elicited by the noise stimulus in preweanling rats was mediated by parasympathetic activation of the heart, (b) the stimulus-elicited increase in heart rate elicited by the noise in periadolescent rats was mediated by parasympathetic withdrawal of the heart, and (c) the noise-induced increase in heart rate in adult rats was primarily mediated by sympathetic activation of the heart.

Malondialdehyde formation in liver mitochondrial and microsomal fractions of vitamin E- and selenium-deficient rats as a function of alpha-tocopherol level: the effect of treatment in vitro with iron.

Weanling rats were given diets with adequate vitamin E and selenium or deprived of one or the other or both, nutrients. After 28 days, liver mitochondrial and microsomal fractions were prepared and alpha-tocopherol (alpha-T) and selenium measured. alpha-Tocopherol fell by eight-fold in the doubly deficient rats and selenium fell three-fold. Malondialdehyde (MDA) was found to be undetectable by a sensitive HPLC method. The fractions were subjected to peroxidative stress in in vitro using 0.5 mM Fe2+/10 mM ADP, and MDA and alpha-T were measured at intervals during 30 min. The results showed that in the mitochondrial fractions there was a lag time of at least 2 min before peroxidation became significant, during which time most of the alpha-T was consumed. In the microsomal fraction the lag phase was very short prior to the establishment of a linear rate of peroxidation, although little alpha-T was used up. It was concluded that the mitochondrial fraction withstood the peroxidative challenge better than the microsomal fraction even though the initial level of alpha-T in the microsomal fraction was about double that in the mitochondrial fraction. Selenium deficiency had no effect on the length of the lag phase of the fractions which therefore appears to be a characteristic of mitochondrial or microsomal fractions.

6-OHDA-treated weanling rats show normal neuroleptic sensitivity as adults on LHSS

Weanling rats receiving 6-hydroxydopamine (6-OHDA) ICV on postnatal days 15–20 and tested as adults have normal lateral hypothalamic self-stimulation locus of rise (LOR) reward thresholds but significantly lower operant motor/performance (MAX) capacity when compared to vehicle-treated controls using the rate-frequency method. These results are comparable to those previously seen in adult rats treated with 6-OHDA on postnatal day 3. In a second test, day 15–20 6-OHDA treated rats were tested as adults with pimozide (0.125–1.0 mg/kg) and showed LOR shifts ranging from 0.06–0.32 log Hz and MAX shifts of 83-47% of baseline. These results were not significantly different at any dose when compared to day 15–20 vehicle-treated rats. This second result contrasts with the pimozide subsensitivity previously reported in day 3 6-OHDA treated rats and suggests that DA depletions made later in neonatal life may involve different forms of recovery than those seen with earlier dopamine depletions.

Intestinal Na+/H+ Exchanger Activity is Up-Regulated by Bowel Resection in the Weanling Rat

Increased Na+/H+ exchanger activity is associated with cellular hyperplasia. Cellular hyperplasia is an adaptive response to small-intestinal resection. Therefore, we hypothesized that the small-intestinal Na+/H+ exchanger activity increases in response to small-intestinal resection. Twenty-one-d-old, male Sprague-Dawley rats were randomly divided to receive either a 70% small intestinal resection (n = 59), or a mid-small intestinal transection (n = 49). Seven d postoperatively, the animals were killed and the Na+/H+ exchanger activity of the intestinal remnants was studied by a well validated brush border membrane vesicle technique. The initial rate of Na+ uptake in the presence of an outwardly directed pH gradient and the Vmax of the amiloride-sensitive Na+ uptake were significantly increased (p < 0.01 and p < 0.001, respectively) in the resection as compared with the transection remnants and to a greater magnitude in the distal as compared with the proximal remnants. Km values were not significantly different. The amiloride-sensitive Na+ uptake in the setting of various intravesicular pH was significantly greater (p < 0.001) in the distal resection as compared with the distal transection remnants, with points of enhanced Na+/H+ exchanger activity of intravesicular pH 6.62 and 6.87, respectively. The presence and activation of the Na+/H+ exchanger's internal modifier site was confirmed by demonstrating the effect of intravesicular pH on Na+ efflux. The present study demonstrates an up-regulation of intestinal Na+/H+ exchange activity in a small-bowel resection model in the weanling rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of dietary protein on selected measures of humoral and cellular immunity in the cotton rat Sigmodon hispidus

Small-mammal populations are subject to unpredictable and often dramatic fluctuations in numbers, but the mechanisms underlying this phenomenon are largely unclear. It has been suggested that protein is an important nutritional factor limiting survival, so we explored the effect of protein intake on the immunocompetence of cotton rats (Sigmodon hipsidus). In vivo and in vitro measures of both humoral and cell-mediated immunity were examined in a series of four protein-feeding trials (with weanlings, juveniles, subadults, and adults), using animals randomly assigned to an isocaloric diet containing either 4 or 16% crude protein. The response of lymphoid organ mass and cellularity to low dietary protein was variable, the spleen being more sensitive to dietary protein than the thymus. The ability of splenic lymphocytes to respond to in vitro stimulation with mitogens was unaffected by dietary protein, while the capacity of weanling and subadult cotton rats fed 4% protein to mount a delayed-type hypersensitivity response was enhanced. Nonspecific immunity (complement activity) was reduced in juveniles fed 4% protein. Dietary protein did not influence the ability of subadults or adults to generate a specific antibody response. These data suggest that cotton rats are less sensitive to dietary protein level than many inbred strains of laboratory rodents, younger animals may be at greater risk, and nutritional history may influence the response of a population to a reduction in available dietary protein.

Splenic autotransplantation provides protection against fatal sepsis in young but not in old rats

Splenectomy increases the risk of contracting infections with high mortality. Thus, splenic tissue should be repaired orthotopically whenever possible. If all attempts fail, splenic autotransplantation might be a suitable method for splenic salvage. The protective function of such transplants in adults has been questioned, leading to a decreased frequency of splenic autotransplantations. However, the regeneration of splenic tissue is better in the young organism than in the old, suggesting that the protection provided by regenerated splenic tissue might be more reliable in children than in adults. In addition, children are at a higher risk in the case of overwhelming postsplenectomy sepsis. The protection warranted by regenerated splenic tissue after autotransplantation at different ages was examined using a highly standardized animal model. Sham operation, splenectomy, and splenic autotransplantation were performed on adult, weanling, and newborn rats, and Streptococcus pneumoniae was applied intranasally 9 months after the operation. After pneumococcal challenge about 80% of the splenectomized animals in the different age groups died of infection, whereas only 20% of the sham operated rats died. Regenerated splenic tissue resulting from splenic autotransplantation performed on adult or weanling rats demonstrated no protective function. However, in newborn rats with transplanted splenic tissue, both survival rate and survival time were increased significantly. Determination of lymphocyte subsets in the blood did not allow the protective role of splenic transplants to be predicted. This study indicates that disappointing results of splenic autotransplantation in adult patients should not lead to false pessimism about the role of this operation in children.

Enriched environment primes forebrain choline acetyltransferase activity to respond to learning experience.

Weanling rats were raised in an enriched or an impoverished environment. The enriched rats subsequently learned the Morris water maze faster than their impoverished counterparts. The enriched rats, both maze-trained and untrained, showed higher choline acetyltransferase (ChAT) activity in the caudate than did the impoverished, untrained rats. Maze training increased caudate ChAT in impoverished rats. Enriched but not impoverished rats showed increased hippocampal and anterior cortical ChAT activity after maze training. Thus, enrichment causes a long-lasting increase in caudate acetylcholine (Ach) synthesis and it also primes cortex and hippocampus to respond to a training experience with increased Ach synthesis.

Influences of postnatal age and dietary nucleotides on plasma fatty acids in the weanling rat.

Dietary nucleotides seem to play a number of physiologic roles during early life. They are improved in the maintenance of the immune system, intestinal maturation, and lipid metabolism. Nucleotides affect the conversion of essential fatty acids into their long-chain polyunsaturated (PUFA) derivatives in both preterm and at-term newborn infants. This work examines the effect of postnatal age and dietary nucleotides on the fatty acid composition of total plasma lipids and lipid fractions in the rat. Weanling rats (21 days old) were divided into three groups. The first group was killed, and the other two groups were fed a standard semipurified diet, and the same diet supplemented with 250 mg each of CMP, UMP, AMP, GMP, and IMP per 100 g of diet for 4 weeks. Advancing postnatal age led to an increase of total plasma fatty acids, especially saturated, and PUFA of the n-6 series, whereas PUFA of the n-3 series decreased. The fatty acid profile of plasma phospholipids (PL) exhibited minor changes, although there was a tendency to show lower levels of saturates and PUFA of the n-3 series and increased levels of PUFA of the n-6 series. Cholesteryl esters showed a response similar to that of PL, although the increase in arachidonic acid (20:4n-6) was significant. For triglycerides, linoleic acid (18:2n-6) and monounsaturates increased their levels, whereas saturates decreased. Dietary nucleotides mediated a significant increase in total plasma fatty acids, namely monounsaturated fatty acids and PUFA of both n-6 and n-3 series as compared with the control group. The relative fatty acid composition of PL and cholesteryl esters was mostly unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary calcium or phosphorus restriction and 1,25-dihydroxyvitamin D administration on rat intestinal 24-hydroxylase.

1,25-Dihydroxyvitamin D-24-hydroxylase (24-hydroxylase) modulates the biological effects of 1,25-dihydroxyvitamin D [1,25-(OH)2D] in tissues. The presence of 24-hydroxylase in intestinal mucosa and the mass of the intestine suggest that the intestine is a major site of catabolism of 1,25-(OH)2D. How intestinal levels of 24-hydroxylase are regulated under various dietary conditions, such as calcium (Ca) or phosphorus (P) restriction, is poorly understood. In a series of trials on weanling and mature rats, the effects of dietary Ca or P restriction were compared with the effects of exogenous 1,25-(OH)2D3 administration on intestinal 24-hydroxylase activity. Exogenous administration of 1,25-(OH)2D3, by single bolus injection or constant infusion, increased intestinal 24-hydroxylase activity significantly. Dietary Ca and P restriction both resulted in increased plasma 1,25-(OH)2D3 concentrations several-fold above control rat values (P less than 0.001) and to levels higher than those achieved by constant infusion of 1.3 ng 1,25-(OH)2D3/h. Dietary Ca restriction increased intestinal 24-hydroxylase 6- to 20-fold above that of rats fed a Ca-replete diet (P less than 0.001). Dietary P restriction had no significant effect on intestinal 24-hydroxylase activity. These data suggest that dietary Ca restriction results in increased plasma levels of 1,25-(OH)2D3, which, in turn, leads to up-regulation of intestinal 24-hydroxylase. Conversely, dietary P restriction prevents 1,25-(OH)2D3-mediated up-regulation of 24-hydroxylase.

Ontogenetic differences in the psychopharmacological responses to separate and combined stimulation of D1 and D2 dopamine receptors during the neonatal to weanling age period.

The psychopharmacological responses to separate and combined stimulation of dopamine D1 and D2 receptors were examined in neonatal (postnatal day 3-4, P3-4), infant (P10-11) and weanling (P21-22) rat pups. Thirty minutes prior to testing rat pups received a subcutaneous (SC) injection of saline, 1.0 (P3-4, P10-11) or 0.5 (P21-22) mg/kg of the D2 agonist quinpirole. Fifteen minutes later all animals received an additional SC injection of 0, 0.01, 0.1, 1.0 or 10.0 mg/kg of the D1 agonist SKF-38393. Pups were tested for 5 min via a time-sampling procedure in a humidity controlled incubator for 3- and 10-day-old animals and in a divided glass aquarium for 21-day-old pups. Although administration of either agonist alone induced increases in forward locomotion and/or sniffing behavior at all test ages, the adult-typical grooming response to SKF-38393 and increase in vertical movements in response to quinpirole were not evident until weaning. Similarly, although combined administration of the agonists induced synergistic responding at each test age, only weanlings exhibited an adult-typical synergistic increase in licking. Thus, although the D1 and D2 receptor subtypes appear to be functionally present and coupled in some fashion throughout the neonatal to weanling age period, ontogenetic differences are evident in the behavioral responses elicited by separate and combined stimulation of these receptor subtypes.

Effects of acute dopamine depletion on responsiveness to D1 and D2 receptor agonists in infant and weanling rat pups.

The behavioral responses to separate and combined administration of the D1 agonist SKF-38393 and the D2 agonist quinpirole following acute dopamine (DA) depletion via alpha-methyl-p-tyrosine (AMPT) or AMPT/reserpine were examined in infant (10-day-old) and weanling (21-day-old) rat pups. At both ages, AMPT pretreatment generally had little impact on D1- or D2-agonist-induced responding, whereas the greater DA depletion observed following AMPT/reserpine pretreatment was generally associated with suppression of both D1 and D2-agonist-typical responding. Thus, whereas in adult animals some degree of D1 receptor activation by endogenous dopamine appears to be necessary for D2 responding but not vice versa (e.g. White et al. 1988), in young animals there appears to be a reciprocal co-dependence of these two receptor subtypes, with extensive DA depletion suppressing responding to both agonists when administered separately. At 10 days of age, some D1 and D2 agonist-induced behaviors that were previously blocked by AMPT/reserpine were reinstated following combined administration of both agonists. In contrast, no clear evidence for reinstatement was seen following administration of the combined agonists to AMPT/reserpine-pretreated weanlings, perhaps due to the induction of potential competing behaviors. Whereas DA depletion blocked many D1- and D2-induced behaviors, such depletion conversely promoted the expression in agonist-treated animals of a number of behaviors that were not normally induced by the agonists in non-depleted animals. These behaviors typically involved an oral component and included grooming and mouthing following SKF-38393 in depleted 10-day-old pups, mouthing following administration of either agonist to depleted weanlings, and probing and intense self-mutilation (forepaw and tongue biting) following the combined agonists in depleted weanlings. This rapid induction of potentiated agonist responsiveness following acute DA depletion early in life may have significant implications with regard to animal models for the developmental disorder of Lesch-Nyhan syndrome.

Partial ureteric obstruction in weanling rats. II. Long-term effects on renal function and arterial blood pressure.

A partial obstruction of the left ureter was created in weanling (3-week-old) rats. Renal function was studied after 7-9 weeks and compared to that in age-matched controls. Arterial blood pressure was found substantially increased. During normal hydration, the hydronephrotic kidney had low excretions of urine, potassium, osmoles and, especially, sodium. The contralateral, intact side showed no compensatory traits. On volume expansion, the hydronephrotic kidney demonstrated an unimpaired reacting capacity, leading to normalization of urine, sodium and osmole excretions and even to supernormal renal blood flow, glomerular filtration and potassium excretion. On the intact side, the excretion of potassium was increased like that on the hydronephrotic one, while excretions of urine, sodium and osmoles were increased even more. The fact that the intact kidney handled most of the urine excretion was interpreted as the result of a mechanism protecting the obstructed kidney from additional pressure insults while homeostasis was maintained. The arterial hypertension may result from the combination of retention of fluid and sodium by the hydronephrotic kidney and the absence of compensation by the intact kidney during normal hydration--like that in everyday life. The functional changes during normal hydration were generally more severe than those we found after obstruction in neonatal and adult rats, in which arterial hypertension was never observed. The clinical implication would be that the kidney may be less tolerant to pressure rises during the infant year. Changes due to obstruction are known to occur rapidly, but after that neither progress nor reverse.(ABSTRACT TRUNCATED AT 250 WORDS)

Bactericidal effects of co-amoxiclav (amoxycillin clavulanic acid) against a Legionella pneumophila pneumonia in the immunocompromised weanling rat.

To evaluate the activity of co-amoxiclav (amoxycillin/clavulanic acid) against Legionella pneumophila in vivo, a model of L. pneumophila pneumonia was developed in weanling rats rendered leukopenic by pre-administration of cyclophosphamide. Assessment of therapy was by lung bacterial counts and histological examination. Amoxycillin was ineffective in reducing bacterial counts in the lungs of infected rats, whereas erythromycin, the standard agent, was significantly more effective (P < 0.01). Co-amoxiclav and erythromycin, administered parenterally, produced significant bactericidal effects (P < 0.01), reducing the counts of L. pneumophila strain 1624 at 96 h to 1.2 log10 cfu/lungs compared with counts of 6 log10 cfu/lungs in the untreated animals. Clavulanic acid was also highly effective in preventing development of the infection, and was as efficacious as co-amoxiclav. Because of the significant reduction in bacterial numbers, a marked reduction in inflammation and consolidation of lung tissue was seen in rats treated with erythromycin, clavulanic acid or co-amoxiclav. The activity of co-amoxiclav was no greater than clavulanic acid alone, and no synergy was noted between the two components. When therapy was delayed until 48 h after infection, co-amoxiclav was as effective as erythromycin, with both treatments reducing bacterial numbers to 3.3 and 3.6 log10 cfu/lungs by 96 h, after only two days of therapy, in comparison with non-treated rats (5.6 log10 cfu/lungs). In a prolonged infection, produced by extending the period of leucopenia, co-amoxiclav and erythromycin were equally effective in preventing growth of the organism, with 1.5 and 1.6 log10 cfu/lungs, respectively, present at 96 h, in contrast to the non-treated rats with 5.7 log10 cfu/lungs (P < 0.01). After cessation of therapy, regrowth of L. pneumophila occurred in the erythromycin-treated group to such a degree that by 168 h, lung viable counts from these rats were significantly higher (4.8 log10 cfu/lungs) than in co-amoxiclav-treated rats (2.1 log10 cfu/lungs) (P < 0.05). Oral therapy of this infection with erythromycin or clavulanic acid, either alone or in combination with amoxycillin, resulted in counts of 3.3, 3.6 and 3.5 log10 cfu/lungs at 96 h, respectively. Although oral therapy was significantly less effective than parenteral therapy (P < 0.05), the bacterial counts in the treated groups were significantly lower than in the non-treated animals. The data show that co-amoxiclav displayed bactericidal activity consistently against intracellular L. pneumophila in vivo.

Maternal Dietary Fat Type Influences the Growth and Fatty Acid Composition of Newborn and Weanling Rats

To determine whether the long-term consumption of different amounts or types of fat by female rats affects the growth and development of their progeny, Wistar rats were fed from weaning either a low fat diet (4.5% by weight) or one of three high fat (32%) diets containing predominantly beef tallow (high saturated fat), corn oil (high polyunsaturated fat) or equal portions of tallow and corn oil (high mixed fat). Offspring were killed at birth or weaning. Weight of newborn pups was lower with maternal consumption of high polyunsaturated fat diets. Carcass composition of newborn pups and body weight of weanling rats was unaffected by maternal diet. The percentage of carcass lipid was greater in weanling rats from all high fat-fed dams. In both newborn pups and weanling rats, percent composition in carcass lipids of 16:0, 16:1 and 18:1 fatty acids generally decreased and 18:2 increased as the high fat maternal diet became more unsaturated. The consumption of diets high in polyunsaturated fatty acids prior to and throughout gestation thus seemed to have a transitory effect on reducing fetal growth in rats.

Do propriospinal projections contribute to hindlimb recovery when all long tracts are cut in neonatal or weanling rats?

Lateral hemisection lesions separated by 1 to 3 spinal segments were made on opposite sides of the midthoracic spinal cord in 1-month-old ( N = 15; weanling operates) and newborn albino rats ( N = 16; neonatal operates). Hindlimb behavior was assessed between 1 and 6 months p.o. for both groups of operates using a protocol and rating system that have previously proved effective in differentiating behavioral recovery of the hindlimbs as a function of age of spinal transection. In addition, at the conclusion of behavioral testing, operates received spinal injections of [ 3H]proline and HRP caudal to the spinal lesions to determine if lesions were complete and if neurons within the region between the two lesions (interlesion zone) projected into the caudal spinal cord. In both groups of operates, neurons were retrogradely labeled within the interlesion zone bilaterally, primarily in laminae VII–VIII. When both lesions were complete lateral hemisections in weanling operates, little behavioral recovery was observed, similar to complete spinal cord transection ( N = 3). However, much greater behavioral recovery was seen, including supporting reactions and locomotor responses, when one or both lesions spared axons along the ventrolateral rim of the white matter. Neurons were retrogradely labeled in the brain stem reticular formation ( N = 12) in these cases. All lesions were complete lateral hemisections in neonatal operates but much greater behavioral recovery was seen than in weanling operates with the same lesions, including supporting, placing, and locomotor responses. In an additional group of eight neonatal operates, the spinal cord rostral to the spinal hemisections was transected at 1 month of age. Supportive, placing, and locomotor responses were seen immediately after recovery from anesthesia and responses returned to pretransection levels in six of eight operates over the 10-day survival period. Fink-Heimer impregnation showed that degeneration argyrophilia from the transection bilaterally filled the interlesion zone but little argyrophilia was seen caudal to this region. Our results indicate that an intact propriospinal circuit remains in both neonatal and weanling operates but does not appear to contribute to hindlimb response development or recovery. The greater behavioral recovery in neonatal operates appears due to intrinsic connections (doral root, interneuronal) continuing to be able to drive the spinal circuitry underlying the spared behaviors.

Primary demyelination induced by exposure to tellurium alters mRNA levels for nerve growth factor receptor, SCIP, 2′,3′-cyclic nucleotide 3′-phosphodiesterase, and myelin proteolipid protein in rat sciatic nerve

Weanling rats fed a diet containing tellurium develop a peripheral neuropathy characterized by a highly synchronous primary demyelination; this demyelination is followed closely by a period of rapid remyelination. The demyelination is related to the inhibition of squalene epoxidase activity, which results in a block in cholesterol synthesis. Expression of mRNA for the major structural proteins of PNS myelin, myelin basic protein and P 0, is coordinately down-regulated during the demyelinating phase and then up-regulated during the remyelinating phase (Toews et al., J. Neurosci. Res., 26 (1990) 501–507). We now report tellurium-induced alterations in gene expression for several proteins which are not major structural components of myelin in the peripheral nervous system. Expression of mRNA for nerve growth factor receptor in sciatic nerve was very low in control animals, but was markedly up-regulated after 3–5 days of exposure to tellurium, a time corresponding to the beginning of demyelination. Levels remained elevated during the subsequent period of remyelination. Expression of mRNA for SCIP (a presumptive transcription factor) was also up-regulated in sciatic nerve following tellurium exposure, with a time course similar to that for nerve growth factor receptor. When examined as a fraction of total RNA, steady-state mRNA levels for 2′,3′-cyclic nucleotide 3′-phosphodiesterase and the myelin proteolipid protein were decreased during the demyelinating phase; however, this decrease could be largely accounted for the increased levels of total RNA. When analyzed on a ‘per nerve’ basis, steady-state mRNA levels for these two proteins were actually increased about 2-fold by 9 days after beginning tellurium exposure. Differences in alterations of mRNA levels between these two ‘myelin-related’ proteins and the two major structural proteins of PNS myelin suggest that in the PNS, 2′,3′-cyclic nucleotide 3′-phosphodiesterase and the myelin proteolipid protein may play roles distinct from their functions in CNS myelin.