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PubMed2005

Galactocerebrosidase-deficient oligodendrocytes maintain stable central myelin by exogenous replacement of the missing enzyme in mice.

Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by genetic deficiency of galactocerebrosidase (GALC) activity. Failure in catalyzing the degradation of its major substrate, galactocerebroside, in oligodendrocytes (OLs) and Schwann cells leads to death of these myelinating cells, progressive demyelination, and early demise of GLD patients. Transplantation of bone marrow cells and umbilical cord blood have been attempted as a means of enzyme replacement and have shown limited success. It remains unknown whether or how these therapies support survival of GALC-deficient OLs and myelin maintenance. We report that, upon transplantation, GALC-deficient OLs from the twitcher mouse, a model of GLD, achieved widespread myelination in the brain and spinal cord of the myelin-deficient shiverer mouse, which was preserved for the life of the host. GALC immunohistochemistry showed direct evidence for GALC transfer from the shiverer environment to the engrafted mutant OLs in vivo. These findings suggest that the mutant OLs can internalize exogenous GALC and maintain stable myelin, demonstrating that exogenous enzyme replacement will be a key strategy in the therapy of GLD.

Animals↗
PubMed2001

The role of leptin in the transition from fetus to neonate.

Leptin is a 16 kDa hormone which has been shown to have a major physiological role in the control of energy balance. Leptin is produced primarily in white adipose tissue, although there is evidence for its production in brown adipose tissue (BAT) and the placenta. BAT is critically important for the initiation of non-shivering thermogenesis in the newborn through the BAT-specific uncoupling protein (UCP), UCPI. This factor is particularly important in lambs in which levels of UCP1 peak at birth, concomitant with a rapid decline in plasma leptin levels. Our studies have examined the effect of acute and chronic administration of leptin to neonatal lambs, investigating effects on colonic temperature, UCP1 and thermogenic potential of BAT. Administration of leptin in sequential physiological doses of 10, 100 and 100 microg to neonatal lambs caused a modest increase in colonic temperature which was not observed in weight-matched vehicle-treated controls. This increase in colonic temperature was not mediated by an increase in either abundance or thermogenic potential of UCPI, as previously shown in adult rodents. UCP1 mRNA levels were 30 % lower in leptin-treated lambs, which is also contradictory to findings in adult rodents. Leptin treatment resulted in a dose-dependent rise in plasma leptin, with levels at the end of the study being almost twenty times greater in leptin-treated animals. To determine whether these findings in neonatal lambs were transient due to the complex milieu of hormones present after birth, we examined the effect of chronic leptin treatment over 6 d. Pairs of lambs were treated daily, from the second to seventh day of life with 100 microg leptin or vehicle. Colonic temperatures of leptin- and vehicle-treated animals remained similar throughout the study. UCP1 abundance was significantly lower in the leptin-treated animals, suggesting that the drop in UCP1 mRNA seen in the previous study had been translated to protein levels. In conclusion, the decline in plasma leptin levels at birth may be a signal to initiate enteral feeding. In lambs, the rapid loss of UCP1 mRNA, which occurs within the first few days of life, appears to be accelerated by leptin administration, possibly stimulating the development of white adipose tissue and generation of body heat through mechanisms other than non-shivering thermogenesis by UCP1 in BAT.

Adipose Tissue, Brown↗
PubMed2002

Peri-operative amino acid administration and the metabolic response to surgery.

General anaesthesia causes hypothermia due to decreased metabolic rate and impaired thermoregulation. Many warming devices are in use to prevent heat loss, but little attention has been paid to stimulating the body's own heat generation. All nutrients raise energy expenditure, and the highest thermic effect is ascribed to amino acids and proteins, 30-40 % in the awake state. Amino acids infused during general anaesthesia exert a thermic effect that is enhanced compared with that in the awake state. At awakening from anaesthesia, post-operative hypothermia may be prevented without shivering. The tissues involved and the mechanisms by which nutrients stimulate heat production are still not completely understood. However, these findings support the existence of an inhibitory action normally exerted by central thermosensors, in order to maintain oxidative metabolism within certain limits, to prevent hyperthermia. During anaesthesia central thermosensors are silenced and, hence, amino acid thermogenesis is exaggerated. The amino acid-induced heat generation during anaesthesia predominantly occurs in extra-splanchnic tissues, most probably in skeletal muscle. It may reflect an increased protein turnover, as both protein breakdown and synthesis are energy-consuming processes known to generate heat. Possibly, amino acid infusion provides substrates, otherwise mobilized from the body's own tissues, needed for wound healing and immunological function. However, other cellular mechanisms may also contribute to this non-shivering thermogenesis.

Amino Acids↗
PubMedDate not supplied

Behavior and muscle performance in heterothermic bats.

Body temperatures of winter-resident Korean bats typically range from 10 degrees to 40 degrees C between August and September and from 3 degrees to 15 degrees C between January and April. To learn how behavior and the motor systems of heterothermic bats respond to this body-temperature variation, we examined whole-organism performance and the temperature-dependence of contractile properties of flight muscle in Murina leucogaster ognevi. In winter and midspring, the lowest limits of body temperature were 8 degrees C for biting and crawling, 16 degrees C for visually observable shivering, 22 degrees C for wing flapping (without powered flight), and 28 degrees C for aerial flight. In summer, the lowest temperature limits changed little for biting and wing flapping, but the temperature limits increased about 3 degrees C for crawling, shivering, and flight. Maximum isometric tetanic tension of the isolated biceps brachii muscle was almost insensitive to tissue temperatures between 10 degrees and 40 degrees C, with an average temperature coefficient of 1.02 in summer and of 0.96 in winter. Rate of tetanic tension production between 10 degrees and 40 degrees C and shortening velocity and power between 15 degrees and 25 degrees C were temperature sensitive, with average temperature coefficients of 1.3-2.3. Seasonal differences in contractile properties within each temperature were not significant, except for maximum tetanic tension at 30 degrees - 40 degrees C. Thus, the motor system of the bats had functional capacity over the range of body temperature experienced in winter to summer. The temperature-dependence of behavior was consistent with muscle physiology. The defensive behaviors, like biting and crawling, observed at 8 degrees - 12 degrees C body temperature could be exerted by using temperature-independent tetanic tension, whereas activities, such as flight, that require power generation would be restricted to higher body temperatures by temperature-sensitive rate properties. Some rate processes appeared to be more temperature sensitive in summer than in winter.

Animals↗
PubMed1987

Structure and expression of myelin basic protein gene sequences in the mld mutant mouse: reiteration and rearrangement of the MBP gene.

The mld mutation on chromosome 18 in the mouse is a putative allele of the shiverer (shi) mutation. We have analyzed the structure of myelin basic protein (MBP) gene sequences in mld DNA by restriction mapping of genomic DNA. The results indicate that the mld chromosome carries two copies of the MBP structural gene, one of which is intact and one of which is interrupted. Genetic analysis indicates that the interrupted gene is close to the intact MBP structural gene and cosegregates with the mld mutation. We have also analyzed the levels of MBP polypeptides and MBP-specific mRNA in wild-type, homozygous and heterozygous shiverer and mld mice and in mice carrying both mutations. The results indicate that both shi and mld are cis-acting codominant mutations that cause severely reduced steady state levels of MBP-specific mRNA and MBP polypeptides in the brain. We have analyzed the total number of oligodendrocytes and the number of MBP-positive oligodendrocytes in mld and shi brain primary cultures. In shi cultures, none of the oligodendrocytes expresses MBP. However, in mld cultures, approximately 5% of the oligodendrocytes express MBP. The nature of the "revertant" mld oligodendrocytes is not known.

Animals↗
PubMed1998

Warming intravenous fluids reduces perioperative hypothermia in women undergoing ambulatory gynecological surgery.

UNLABELLED: We evaluated whether warming i.v. fluids resulted in less hypothermia (core temperature < 35.5 degrees C) compared with room-temperature fluids. Thirty-eight adult outpatients undergoing elective gynecological surgery of > 30 min were randomized to two groups: fluid warming at 42 degrees C or control (room temperature fluids at approximately 21 degrees C). All patients received general anesthesia with isoflurane, tracheal intubation, standard operating room blankets and surgical drapes, and passive humidification of inspired gases. Tympanic membrane (core) temperatures were measured at baseline and at 15-min intervals after induction. The incidence of shivering and postoperative requirement for meperidine and/or radiant heat were evaluated. Core temperatures were lower in the control compared with the warm fluid group at the end of surgery (35.6 +/- 0.1 degrees C vs 36.2 +/- 0.1 degrees C; P < 0.05). More patients had final core temperature < 35.5 degrees C in the control compared with the warm fluid group (35% vs 0%; P < 0.05). There were no differences in time to discharge from the postanesthesia care unit or the incidence of shivering between the groups. We conclude that fluid warming, in conjunction with standard heat conservation measures, was effective in maintaining normothermia during outpatient gynecological surgery; however, there was no improvement in patient outcome. IMPLICATIONS: Women who received i.v. fluid at body temperature had significantly higher core temperatures during and after outpatient gynecological surgery compared with women who received i.v. fluids at the temperature of the operating room.

Adult↗
PubMed2000

Age-related thermoregulatory differences in a warm operating room environment (approximately 26 degrees C).

UNLABELLED: Inadvertent hypothermia occurs frequently at typical ambient operating room (OR) temperatures, especially in elderly patients receiving general anesthesia. The aims of the current study were to 1) determine the incidence and magnitude of core hypothermia in an unusually warm OR environment, and 2) to assess age-related differences in perioperative thermoregulatory responses under these circumstances. Forty patients receiving general anesthesia for orthopedic surgical procedures (20 younger patients, 20-40 yr old) and (20 older patients, 60-75 yr old) were enrolled. Mean ambient temperature in the ORs was 25.8 degrees +/- 0.2 degrees C. Core temperature, vasoconstriction, and shivering were compared in the younger and older age groups. Mean core temperature on admission to the postanesthesia care unit was not significantly different in the younger (36.7 degrees +/- 0.1 degrees C) and older (36.4 degrees +/- 0.1 degrees C) age groups. Only 10% of patients (n = 4, 1 younger, 3 older) were admitted with a core temperature <36.0 degrees C. Only 2% of patients (n = 1, older group) had a core temperature <35.5 degrees C. This very mild degree of hypothermia was associated with postoperative vasoconstriction in 80% of the younger and 55% of the older patients (P = 0.18). Postoperative shivering occurred in 40% of the younger patients and in 10% of the older patients (P = 0.06). In summary, an ambient OR temperature near 26 degrees C (79 degrees F) is effective in preventing core hypothermia during general anesthesia regardless of patient age. Even very mild postoperative hypothermia may initiate thermoregulatory responses. IMPLICATIONS: By increasing ambient temperature in the operating room to 26 degrees C (79 degrees F), the incidence of core hypothermia can be dramatically reduced in both younger and older patients.

Adult↗
PubMed1989

Changes in ventilation, oxygen uptake, and carbon dioxide output during recovery from isoflurane anesthesia.

Recovery from inhalation anesthesia is often marked by the occurrence of postoperative tremor that resembles shivering, which is known to be associated with an increase in oxygen uptake (VO2), CO2 output (VCO2), and minute ventilation (VE). This study determined the time course of the ventilatory changes observed during the first hour of recovery from isoflurane anesthesia. Ten patients (ASA PS 1) scheduled for minor orthopedic surgery (knee arthroscopy) were included in this study. Anesthesia was induced with thiopental (5 mg/kg) and maintained with 70% N2O and isoflurane (1-2%) in oxygen, allowing spontaneous ventilation. In the recovery room, after N2O had been discontinued, patients were connected to a Beckman Metabolic measurement cart, which allowed a continuous monitoring of VE, VO2, VCO2, and PETCO2. Postoperative tremor was observed in all patients within 7.1 +/- 1.2 min (mean +/- SEM) after isoflurane discontinuation and was associated with a marked increase in the following: VO2, from 173 +/- 26 ml/min at the end of anesthesia to 457 +/- 88 ml/min; VCO2, from 149 +/- 18 ml/min at the end of anesthesia to 573 +/- 98 ml/min; and VE, from 6.8 +/- 0.7 l/min at the end of anesthesia to 16.6 +/- 2.8 l/min (values obtained 20 min after isoflurane discontinuation). In three patients during intense shivering, VO2, VCO2, and VE reached peak values higher than 800 ml/min, 1,300 ml/min and 30 l/min, respectively. This study shows that postoperative tremor following isoflurane anesthesia may be associated with prolonged and large increases in oxygen uptake, CO2 output, and minute ventilation.

Adolescent↗
PubMed1998

Desflurane reduces the febrile response to administration of interleukin-2.

BACKGROUND: Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane-induced anesthesia produces a dose-dependent inhibition of the febrile response. METHODS: Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/ kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated-measures analysis of variance and Scheffé's F tests. RESULTS: Values are presented as mean +/- SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/- 2.0 degrees C x h on the control day to 2.1 +/- 2.3 degrees C x h during 0.6 MAC and to -1.4 +/- 3.1 degrees C x h during 1.0 MAC desflurane-induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a dose-dependent fashion: 38.6 +/- 0.5 degrees C on the control day, 37.7 +/- 0.7 degrees C during 0.6 MAC and 37.2 +/- 1.0 degrees C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering. CONCLUSIONS: Desflurane-induced anesthesia produced a dose-dependent decrease in integrated and peak core temperatures after administration of pyrogen, with 1.0 MAC essentially obliterating fever. Anesthetic-induced inhibition of the pyrogenic response is therefore one reason that fever is an inconsistent clinical response to inflammation during surgery.

Adult↗
PubMed1991

Poikilothermia in man: pathophysiology and clinical implications.

Poikilothermia, the inability to maintain a constant core temperature independent of ambient temperature, markedly influences both the mental and physical function of affected patients; furthermore, prolonged hypothermia can induce numerous complications. To establish the pathophysiology of thermoregulation underlying poikilothermia in man, we compared 4 women with acquired poikilothermia, with 9 female control subjects. The activity of the main thermoregulatory effector mechanisms was assessed in a thermoneutral environment, and during subsequent cold stress and heat exposure. At thermoneutrality the patients had a significantly lower rectal temperature and resting metabolic rate compared with the controls; no patient showed peripheral vasoconstriction or shivering. Cooling revealed markedly reduced peripheral vasoconstriction in 3 patients and failure of the metabolic response in 2 patients; unlike controls, no patient exhibited shivering. Heat challenge revealed severely reduced capacity for heat dissipation in all patients. We conclude that in patients with poikilothermia, the mechanisms for both heat conservation and heat dissipation are seriously attenuated. Careful monitoring of the core temperature and adequate measures to maintain normothermia are of great importance in patients with poikilothermia in order to provide adequate treatment, improve the quality of life, and prevent serious complications.

Adipose Tissue↗
PubMed2004

A pilot-randomized comparison of sublingual misoprostol with syntometrine on the blood loss in third stage of labor.

BACKGROUND: To compare sublingual misoprostol with intravenous syntometrine use during third stage of labor by measuring the blood loss. METHODS: Sixty women were randomized to receive either 600 micro g misoprostol sublingually or 1 ml syntometrine intravenously during the third stage of labor after spontaneous vaginal delivery. For those with risk factors of postpartum hemorrhage such as medical induction or augmentation of labor, previous third stage complications were excluded. The blood loss in labor was measured by the alkaline-hematin method, and differences in hemoglobin before and after delivery were compared. RESULTS: There was no significant difference in the median measured blood loss between the misoprostol group and the syntometrine group (280 versus 226 ml, p = 0.45). The change in hemoglobin was comparable between the two groups. There were more women in the misoprostol group who required additional oxytocics, but the difference was not statistically significant. A major complication occurred in one patient in the misoprostol group with blood loss in excess of 1000 ml. The incidence of side effects such as shivering and pyrexia in women receiving misoprostol was significantly higher than that in the syntometrine group. CONCLUSION: The use of sublingual misoprostol or intravenous syntometrine in spontaneous vaginal delivery resulted in a comparable amount of blood loss. Transient side effect such as fever and shivering which resolved within a day occurred more frequent to those who received sublingual misoprostol.

Administration, Sublingual↗
PubMed1992

Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha.

Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r.BoTNF-alpha, r.HuTNF-alpha and LPS in dwarf goats may indicate that both recombinant tumour necrosis factors have some homology with caprine TNF-alpha.

Acute-Phase Reaction↗
PubMed1985

Sublingual buprenorphine for premedication and postoperative pain relief in orthopaedic surgery.

The effect of sublingual buprenorphine (Temgesic) as a premedicant and for postoperative pain relief compared with morphine/pethidine was studied in 50 patients scheduled for elective surgery of the knee joint. Twenty-five patients received buprenorphine 0.4 mg sublingually 1 h before surgery and the same dose on demand postoperatively. Twenty-five patients were given morphine intramuscularly (7.5 mg or 10 mg to females and males respectively) 1 h preoperatively. This group received pethidine (75 mg) intramuscularly on demand postoperatively. All the patients were anaesthetized with halothane N2O/O2 after induction with thiopentone. No significant differences were found with regard to sedation, dizziness, nausea and vomiting during the study period. Emergence shivering, confusion and restlessness just after termination of the operation were equal in the two groups. In the recovery room, however, there was a higher frequency of shivering (P less than 0.05) in the morphine group. During the first 24 h postoperatively the buprenorphine group was given an average of 3.8 doses compared with 2.3 in the pethidine group (P greater than 0.05). It is concluded, that buprenorphine sublingually is as good as morphine intramuscularly for premedication and therefore should be recommended to patients who wish to avoid injections. For postoperative pain relief the initial dose of buprenorphine should be given intravenously. Only minor and unimportant side effects were seen.

Administration, Oral↗
PubMed1987

Heating efficacy of external heat supply during and after open-heart surgery with hypothermia.

Heat balance after cardiac surgery with hypothermic cardiopulmonary bypass (CPB) was studied in 156 patients. In spite of rewarming during CPB there was residual hypothermia at the end of operation. This heat deficit could not be prevented by intraoperative use of a heating mattress at 38 degrees C and/or heated (39 degrees C) humidified inspired gases. Postoperatively, in four groups of patients, the core and finger skin temperatures were recorded and the mean skin and mean body temperatures and heat balance were calculated. Heating of humidified inspired gases (n = 22) gave little improvement in the time course of the temperatures and heat balance as compared with that in a control group with no external warming postoperatively (n = 49). A thermal ceiling (a low-temperature radiator suspended above the bed and providing radiant heat (n = 35] significantly increased the measured temperatures, which were restored to normal earlier than those in the controls. Also, with this radiant heat postoperative shivering was almost abolished. With a combination of radiant heat and heated, humidified gases (n = 50), the postoperative heat balance was improved somewhat further. For patients treated with radiant heat, postoperative rewarming was accomplished in a shorter time and almost without active endogenous muscular thermogenesis, as was evident by the great reduction in postoperative shivering.

Anesthesiology↗
PubMed1987

Postoperative ventilatory and circulatory effects of heating after aortocoronary bypass surgery. Postoperative external heat supply.

The effects of postoperative external heat supply on shivering, oxygen uptake, carbon dioxide production, ventilatory requirements and haemodynamic variables were studied postoperatively after aortocoronary bypass surgery in 24 men with stable angina pectoris. After hypothermic cardiopulmonary bypass (CPB) at 25 degrees C, the patients were rewarmed to a nasopharyngeal temperature of at least 38 degrees C, resulting in a rectal temperature of about 34 degrees C before termination of CPB. Twelve patients, forming the control group, were given no other external heat supply. In another group (n = 12), the "radiant heat supply group", additional external heat was provided postoperatively, the main source of which was a thermal ceiling supplemented with heated, humidified respiratory gases. In this latter group the postoperative rewarming was accomplished earlier and was converted into a mainly passive process. Shivering, oxygen uptake, CO2 production and ventilation volumes were significantly reduced compared with the control group. Cardiac index and stroke index were higher and systemic oxygen extraction was lower in the radiant heat supply group. Postoperative hypertension and vasoconstriction were greatly decreased, suggesting that residual hypothermia is an important cause of the postoperative vasoconstriction.

Anesthesia↗
PubMed1991

A comparison between morphine, meperidine and ketobemidone in continuous intravenous infusion for postoperative relief.

Morphine, meperidine and ketobemidone used in continuous i.v. infusion for postoperative pain relief were compared in a double-blind, controlled, prospective study in 81 consecutive consenting adult patients after open-heart surgery, with permission from the hospital ethics committee. During the first postoperative period, the infusion rates were fixed. Later on, when the infusion rate could be regulated according to individual patient needs, the variation in infusion rate was large, in accordance with earlier studies. No significant differences were demonstrated between the three analgesics with respect to efficacy of analgesia or side effects like shivering, nausea or vomiting. Respiratory depression following extubation was not observed. During shivering, there was a significant increase in the arterio-mixed venous difference of oxygen in all groups. The amounts of opioids used were relatively small compared to amounts used in patients following abdominal surgery. When interviewed some days after surgery, 18/74 patients remembered moderate pain and 11 severe pain during the stay in the ICU.

Double-Blind Method↗
PubMed2004

Myelination triggers local loss of axonal CNR/protocadherin alpha family protein expression.

The cadherin-related neuronal receptor (CNR)/protocadherin (Pcdh) alpha family is one of the diverse protocadherin families expressed in developing axons. We observed a strong axonal expression of these proteins at late embryonic and early postnatal stages corresponding to regions where fibers had not yet been myelinated. We therefore followed the postnatal localization of CNR/Pcdh alpha protein in major axonal tracts, such as the internal capsule, lateral olfactory tract, and optic nerve, and found that its axonal localization was dramatically lost in parallel with the increased expression of myelin markers. Moreover, the hypomyelinated optic nerve tracts of the myelin-deficient Shiverer mouse exhibited elevated levels of CNR/Pcdh alpha expression. These axonal expression patterns of CNR/Pcdh alpha in wild-type and Shiverer mice were similar to those of growth associated protein 43 (GAP-43) and L1, both of which are associated with axonal maturation. Thus, myelination may be a trigger for the local loss of axonal CNR/Pcdh alpha protein, and this process may be important in the maturation of neural circuits.

Age Factors↗
PubMed1989

Wild mice in the cold: some findings on adaptation.

The house mouse, Mus domesticus, can thrive in natural environments much below its optimum temperature. Thermogenesis is then above that at more usual temperatures. In addition, body weight, and the weights of brown adipose tissue and the kidneys, may be higher than usual. In free populations of house mice cold lowers fertility and may prevent breeding. Other possible limiting factors on breeding are food supply, shelter for nesting and social interactions. In captivity, wild-type house mice exposed to severe cold (around 0 degrees C) at first adapt ontogenetically by shivering and reduced activity. But raised thermogenesis is soon achieved without shivering; nest-building improves; and readiness to explore may be enhanced. Endocrine changes probably include, at least initially, a rise in adrenal cortical activity and in catecholamine secretion. Some females become barren, but many remain fertile. The maturity of fertile females is, however, delayed and intervals between births are lengthened; nestling mortality rises. A limiting factor during lactation may be the capacity of the gut. Similar adaptive changes are observed during winter in some species of small mammals that do not hibernate. But neither the house mouse nor other species present a single, universal pattern of cold-adaptation. Wild-type mice bred for about 10 generations in a warm laboratory environment (20-23 degrees C) change little over generations. In cold they become progressively heavier and fatter at all ages; they mature earlier, and nestling mortality declines. The milk of such 'Eskimo' females is more concentrated than that of controls. If 'Eskimo' mice are returned to a warm environment, they are more fertile, and rear heavier young, than controls that remained in the warm. Despite the heavier young, litter size is not reduced: it may be increased, probably as a result of a higher ovulation rate. Parental effects have been analyzed by cross-fostering and hybridizing. Survival, growth and fertility are all favourably influenced by the intra-uterine and nest environments provided by 'Eskimo' females. 'Eskimo' males are also better fathers. Hence after ten generations the phenotype of cold-adapted house mice shows the combined effects of (a) an ontogenetic response to cold, (b) a superior parental environment and (c) a change genotype. The secular changes in the cold that lead to this phenotype give the appearance of evolution in miniature; but it is equally possible that they represent a genetical versatility that allows rapid, reversible shifts in response to environmental demands.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗