Biomedical subjects

Bogdan Sadowski

Publications and source records attributed to Bogdan Sadowski.

7 recordsLinked to original sources

PubMed2003

Analgesia induced by swim stress: interaction between analgesic and thermoregulatory mechanisms.

Exposure of an animal to stressful stimuli, perceived by the animal as a threatening, emergency condition, elicits a transient decrease of pain sensitivity, which often affects thermoregulatory mechanisms in the threatened organism. We studied the interaction between emergency and thermoregulatory components of swim stress in developing swim stress-induced analgesia (SSIA). The subjects were mice selectively bred for high analgesia (HA) induced by swimming in 20 degrees C water, and displaying profound swim hypothermia. The mice were acclimated to one of the following conditions: (1) ambient cold (5 degrees C, mimicking the thermal component of swim stress); (2) daily 3-min swimming at 32 degrees C (mimicking the emergency, emotional in nature, component of swim stress), or (3) daily swimming at 20 degrees C (a combination of both emergency and thermal component of swim stress). Following each of the procedures the analgesia induced by swimming in 20 degrees C water and by acute exposure to -2.5 degrees C in helium/oxygen (Helox) atmosphere was measured. Analgesia was also assessed in a group of naive mice immersed in 20 degrees C shallow water with the purpose of eliminating the emergency condition, but assuring the animal's contact with the cold water environment. Cold acclimation markedly attenuated Helox-induced analgesia (HIA) without affecting SSIA, whereas repeated swims attenuated SSIA without affecting HIA. The results suggest that hypothermia is the only stimulus eliciting HIA, while the emergency condition of swimming is essential for inducing SSIA. The significantly lower magnitude of SSIA in mice acclimated to repeated swims in 20 degrees C than in 32 degrees C water suggests that SSIA develops due to an interaction between the emergency and hypothermic components of swim stress. This is further supported by a greater hypothermia and greater analgesia in freely swimming than in immersed naive mice.

Acclimatization↗

PubMed2003

Cytogenetic comparison of the sensitivity to mutagens in mice selected for high (HA) and low (LA) swim stress-induced analgesia.

Sensitivity to mutagens was studied in mouse lines selectively bred for high analgesia (HA) and for low analgesia (LA) induced by 3-min swimming in 20 degrees C water. Apart from pain-related traits HA mice also manifest, as compared to the LA line, higher emotionality in various behavioural tests, and cope worse with the hypothermic challenge of swimming in cold water. In the present study HA mice appeared more susceptible to the mutagenic effect of whole-body gamma-radiation and mitomycin-C injection. Both treatments caused higher frequencies of chromosomal aberrations and micronucleus in bone marrow cells in the HA than in the LA line. The results are discussed in terms of a genetic correlation between animals' susceptibility to environmental stressors and the mechanism of mutagenesis. As shown by our recent molecular study, the selection for magnitude of swim analgesia has differentiated the parental outbred population into two distinct genotypes characterised by specific minisatellite and microsatellite sequences for each line, which may be genetic markers of particular traits. We conceive that the breeding strategy, along with the differentiation of stress-related phenomena, has altered the frequencies of genes controlling DNA repair in each line.

Analgesia↗

PubMed2003

Effect of cold acclimation and repeated swimming on opioid and nonopioid swim stress-induced analgesia in selectively bred mice.

Swiss-Webster mice selectively bred for high swim stress-induced analgesia (SSIA) were exposed to continuous ambient cold (5 degrees C) for 6 weeks or to daily 3-min swims for 14 consecutive days either in 20 or 32 degrees C water. Thereafter, mice subjected to the particular procedure were injected intraperitoneally with 10 mg/kg of naltrexone HCl and were tested for modification of the opioid and nonopioid component of SSIA. SSIA was reduced following swims at either water temperature and was antagonized by naltrexone to greater extent than in nonswimming mice. Thus, the nonopioid (i.e. naltrexone-resistant) portion of the overall SSIA was significantly reduced, whereas the opioid (naltrexone-sensitive) portion became relatively augmented. In contrast, SSIA differed neither in magnitude nor in sensitivity to naltrexone between cold-acclimated and unacclimated mice. Swim hypothermia as well as the nonopioid component of SSIA were decreased after repeated swimming at 32 and 20 degrees C, but remained unchanged after cold acclimation. This argues for the essential role of an extrathermal, probably emotional in nature, factor not only in the elicitation of nonopioid SSIA, but also in the modulation of thermoregulatory processes during swimming. We suggest that the emergency component of swim stress, together with initial moderate hypothermic challenge, first produces the opioid form of SSIA, and subsequently, as the swim continues, also affects the thermoregulatory processes maintaining thermal homeostasis. This causes further increase in swim hypothermia and raises its stressing property to induce the nonopioid form of SSIA.

Acclimatization↗

PubMed2003

Chromosomal NOR activity in mice selected for high and low swim stress-induced analgesia.

Metaphase nucleolar organizer region (NOR) activity was studied in mouse lines selectively bred for high analgesia (HA) and for low analgesia (LA) induced by 3-min swimming in 20 degrees C water. Apart from pain-related traits, HA mice also manifest, as compared to the LA line, higher emotionality in certain behavioral tests and are less capable of coping with the hypothermic challenge of swimming in cold water, in addition to being more susceptible to the mutagenic effect of whole-body gamma-radiation and mitomycin C injection. We here compared NOR activity in HA and LA mice. A statistically significant difference (p < or =.01) was detected in mean silver-stained nucleolar number/cell between the HA and LA lines, being lower for HA mice. We propose that the breeding strategy, along with the differentiation of stress-related phenomena, has altered the activity of genes coding rRNA and that this activity is important in controlling DNA repair in each line. It is concluded that quantitative studies of nucleolar changes may be useful in evaluating the biological reactivity to stress stimuli.

Analgesia↗

PubMed2002

Differential metabolic capacity of mice selected for magnitude of swim stress-induced analgesia.

Maximum oxygen consumption (Vo(2)) elicited by swimming in 20 degrees C water or by exposure to -2.5 degrees C in helium-oxygen (Helox) atmosphere is higher in mice selected for low (LA) than for high (HA) stress-induced analgesia (SIA) produced by swimming. However, this line difference is greater with respect to swim- than to cold-elicited Vo(2). To study the relationship between the analgesic and thermogenic mechanisms, we acclimated HA and LA mice to 5 degrees C or to daily swimming at 20 or 32 degrees C. Next, the acclimated mice were exposed to a Helox test at -2.5 degrees C and to a swim test at 20 degrees C to compare Vo(2) and hypothermia (DeltaT). Cold acclimation raised Vo(2) and decreased DeltaT. These effects were similar in both lines in the Helox test but were smaller in the HA than in the LA line in the swim test. HA and LA mice acclimated to 20 or 32 degrees C swims increased Vo(2) and decreased DeltaT elicited by swimming, but only HA mice acclimated to 20 degrees C swims increased Vo(2) and decreased DeltaT in the Helox test. We conclude that the between-line difference in swim Vo(2) results from a stronger modulation of thermogenic capacities of HA mice by a swim stress-related mechanism, resulting in SIA. We suggest that the predisposition to SIA observed in laboratory as well as wild animals may significantly affect both the results of laboratory measurements of Vo(2) and the interpretation of its intra- and interspecific variation.

Acclimatization↗

PubMed1995

One or two genetic loci mediate high opiate analgesia in selectively bred mice.

The analgesic responses of humans and laboratory animals are characterized by substantial individual differences. The genetic basis of this variability can be studied experimentally in rodents using a program of selective breeding. One such program selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on the hot-plate (56 degrees C) test in Swiss-Webster mice. These lines, which have been selectively bred for more than 25 generations, display markedly divergent opioid-mediated SSIA (3-min swims in 38 degrees C water), morphine analgesia (10 mg/kg, i.p.), and analgesia to the kappa-receptor agonist, U-50,488H (30 mg/kg, i.p.). The present study investigated the mode of inheritance of these opioid analgesias in HA and LA mice, using Mendelian genetic analyses. We report that the differential sensitivity of HA and LA mice to each of these analgesic manipulations appears to be determined oligogenically, by one or at the most two major genetic loci. The loci associated with each type of analgesia do not co-segregate, however, indicating that three distinct oligogenic effects have been identified. These findings suggest that the genetic determination of analgesic mechanisms may have simple components and as such may be amenable to further analysis using molecular genetic techniques.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMedDate not supplied

[Lactoferrin in the central nervous system].

Lactoferrin (LF) is a protein secreted by the tissues of ectodermal origin. Its structure is similar to transferrin. LF appeared to be multifunctional, but its main functions are connected with the natural defense system of mammals. The biological role and origin of LF within brain in normal and disease processes are as yet uncharted. LF expression is greatly upregulated during neurodegenerative disorders and in elderly brains. LF may exert an antiinflammatory function via its inhibitory effect on hydroxyl radical formation. By antioxydative properties, LF prevents DNA damage and consequently tumor formation in the CNS. Moreover, LF specifically transactivates the p53 tumor suppressor gene. LF suppresses distress perception via opioid mediated mechanism and prevents a decrease of the immune system activity caused by psychosocial stress. Furthermore, LF possibly modulates behavior in man and in animals.

Alzheimer Disease↗