Dataset Information

Voluntary Exercise Rescues the Spatial Memory Deficit Associated With Early Life Isoflurane Exposure in Male Rats.

ABSTRACT: BACKGROUND:Early life anesthesia exposure results in long-term cognitive deficits in rats. Environmental enrichment consisting of social housing, a stimulating environment, and voluntary exercise can rescue this deficit. We hypothesized that exercise alone is sufficient to rescue the cognitive deficit associated with perinatal anesthesia. METHODS:Postnatal day 7 male rats (P7) underwent isoflurane (Iso) or sham exposure and were subsequently weaned at P21. They were then singly housed in a cage with a running wheel or a fixed wheel. After 3 weeks of exercise, animals underwent behavioral testing for spatial and recognition memory assessments. Animals were killed at various time points to accomplish either bromodeoxyuridine (BrdU) labeling or quantitative real-time polymerase chain reaction (qRT-PCR) to quantify brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) levels. RESULTS:Postweaning voluntary exercise rescued the long-term spatial memory deficit associated with perinatal Iso exposure. Iso-sedentary animals did not discriminate the goal quadrant, spending no more time than chance during the Barnes maze probe trial (1-sample t test, P = .524) while all other groups did (1-sample t test, PIso-exercise = .033; Pcontrol [Con]-sedentary = .004). We did not find a deficit in recognition memory tasks after Iso exposure as we observed previously. BrdU incorporation in the adult hippocampus of Iso-sedentary animals was decreased compared to sedentary controls (Tukey P = .005). Exercise prevented this decrease, with Iso-exercise animals having more proliferation than Iso-sedentary (Tukey P < .001). There was no effect of exercise or Iso on BDNF mRNA in either the cortex or hippocampus (cortex: FExercise[1,32] = 0.236, P = .631; FIso [1,32] = 0.038, P = .847; FInteraction [1,32] = 1.543, P = .223; and hippocampus: FExercise[1,33] = 1.186, P = .284; FIso [1,33] = 1.46, P = .236; FInteraction[1,33] = 1.78, P = .191). CONCLUSIONS:Exercise restores BrdU incorporation and rescues a spatial memory deficit after early life anesthesia exposure. This demonstrates sufficiency of exercise alone in the context of environmental enrichment to recover a behavioral phenotype after a perinatal insult.

SUBMITTER: Chinn GA

PROVIDER: S-EPMC6800827 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Voluntary Exercise Rescues the Spatial Memory Deficit Associated With Early Life Isoflurane Exposure in Male Rats.

Chinn Gregory A GA Sasaki Russell Jennifer M JM Banh Esther T ET Lee Saehee C SC Sall Jeffrey W JW

Anesthesia and analgesia 20191101 5

<h4>Background</h4>Early life anesthesia exposure results in long-term cognitive deficits in rats. Environmental enrichment consisting of social housing, a stimulating environment, and voluntary exercise can rescue this deficit. We hypothesized that exercise alone is sufficient to rescue the cognitive deficit associated with perinatal anesthesia.<h4>Methods</h4>Postnatal day 7 male rats (P7) underwent isoflurane (Iso) or sham exposure and were subsequently weaned at P21. They were then singly ho ...[more]

PMID: 31517674

Similar Datasets

Project description:Recent changes in demographic patterns of drug use have resulted in the increased non-medical use of prescription opiates. These users are younger and more likely to be female, which has the potential for increasing rates of in utero exposure. Therefore, we developed a rat model that simulates a prescription opiate-dependent woman who becomes pregnant. Adult female Sprague-Dawley rats were treated for 30 days via oral gavage with ascending doses of oxycodone HCl up to a final dose of 15mg/kg/day, which was maintained during breeding and gestation. Controls were treated with water. The adult male offspring of these treated dams were tested on the radial arm maze, the Morris water maze (with a short and a long intertrial interval), and a spatial T-maze. Prenatal oxycodone exposure led to a deficit in the radial arm maze characterized by a greater number of reference memory errors, especially in the beginning of testing. In contrast, in the T-maze, prenatal oxycodone-exposed rats learned the task as well as well as the prenatal water controls. However, they had a modest deficit in retention of the task when assessed 5 days after acquisition training ended. For the Morris water maze, the intertrial interval affected the pattern of learning. While there was no deficit when the training had a short intertrial interval, when there was a long intertrial interval, prenatal oxycodone-exposed rats had poorer acquisition. The spatial learning deficit was characterized by and increased latency to find and a greater distance traveled to the platform in the prenatal oxycodone-exposed rats. These data were corroborated by analysis of the behavioral search strategy, which showed a decreased use of spatial strategies and an increase in non-spatial strategies, especially wall-hugging, in prenatal oxycodone-exposed rats as compared to prenatal water control rats on day 2 of acquisition. These results indicate that prenatal oxycodone exposure consistently impairs learning and memory in a battery of spatial tasks.

Project description:Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer's disease (AD). Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause AD-like neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocampal autophagy in aged rats. Aged Sprague-Dawley rats (20 months old) were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze (4 trials/day for 5 consecutive days). Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B (LC3B), as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3B-II, and p62 at 24 h post-anesthesia between the 1-h isoflurane-exposed rats and their controls (P >0.05). Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 post-anesthesia and less time spent in the target quadrant than sham-exposed animals (P <0.05). These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane (P <0.01 and P <0.05). Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease within 12-24 h post-anesthesia (P <0.05). Hippocampal p62 peaked at 6 h but subsequently resolved. These results from our pilot in vivo study support a duration-dependent relationship between 1.5% isoflurane exposure, and spatial cognitive function as well as hippocampal phagophore formation.

Project description:Background: Adolescence is a period of time characterized by the onset of puberty and is marked by cognitive and social developments and gross physical changes that can play a role in athletic performance. Sex differences are present with differences in body size, height, physiology and behavior which contribute to differences in athletic performance as well. Pre-clinical studies representing this active group are lacking. Methods: Acute and chronic effects of exercise were evaluated. Male and female adolescent rats were given voluntary access to a running wheel for 10 consecutive days. Running behavior (males and females) and estrous cycling (females only) were analyzed daily. A second group was given 10 days of voluntary access to a running wheel, then rested for 10 days to determine the long-term effects of exercise on the adolescent brain. Brain and muscle tissue were harvested at 10 and 20 day time points to understand exercise-dependent changes in mitochondrial activity and neuroplasticity. Animal cohorts were carried out at two different sites: University of California Los Angeles and Pepperdine University. Results: On average, running distance, intensity of run, and length of running bout increased for both male and female rats across the 10 days measured. Females ran significantly further and for longer intervals compared to males. Cortical and muscle expression of PGC1α showed similar levels at 10 days regardless of sex and exercise. There was a significant increase in expression at 20 days in all groups correlating with body size (p's < 0.05). Cortical and hippocampal levels of BDNF were similar across all groups, however, BDNF was significantly higher in exercised females at the acute compared to long-term time point. Discussion: Adolescent rats allowed 10 days of exercise show changes in physiologic function. There are sex differences in running behavior not impacted by sex hormones. These results are important to further our understanding of how exercise impacts the adolescent brain.

Dataset Information

Voluntary Exercise Rescues the Spatial Memory Deficit Associated With Early Life Isoflurane Exposure in Male Rats.

Publications

Voluntary Exercise Rescues the Spatial Memory Deficit Associated With Early Life Isoflurane Exposure in Male Rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure