One aspect of successful aging is maintaining cognitive functioning; that includes both subjective cognitive functioning and objective cognitive functioning even in lieu of subtle cognitive deficits that occur with normal, non-pathological aging. Age-related cognitive deficits emerge across several domains including attention, memory, language, speed of processing, executive, and psychomotor, just to name a few. A primary theory explaining such cognitive deficits is cognitive reserve theory; it posits that biological factors such as demyelination and oxidative stress interfere with neuronal communication which eventually produces observable deficits in cognitive functioning. Therefore, it is important to maintain or improve cognitive reserve in order to augment cognitive functioning in later life. This article provides a general overview of the principles of geroneuropsychology along with implications for nursing practice and research.
Stress during times of rapid development is a risk factor for Major Depressive Disorder, a mood disorder that disproportionately affects women. We developed an adolescent chronic restraint stress (aCRS) protocol using female rats to address the impact of adolescent stress on female adult depressive-like behavior. Animals were divided into 4 treatment groups: not restrained:saline (NRSAL), not restrained:desipramine (NRDES), restrained:saline (RSAL), and restrained:desipramine (RDES). NRSAL and NRDES rats were housed in a separate colony room from RSAL and RDES rats. All animals were weighed and handled daily. Beginning postnatal day (PND) 34(±1), RSAL and RDES rats were restrained for 1 hour daily for 14 consecutive days. Beginning PND 55(±1), NRDES and RDES rats were given subcutaneous desipramine (5 mg/kg), which served as a positive control, daily for 14 consecutive days. During that same time period, NRSAL and RSAL rats were given subcutaneous saline daily. aCRS (RSAL and RDES) rats showed significantly attenuated weight gain compared with nonrestrained (NRSAL and NRDES) rats during the restraint period. Weight gain normalized after the final restraint session. Behavioral testing took place PND 68-69(±1), and included open field testing, the elevated plus maze, locomotor activity, and the forced swim test (FST). RSAL rats showed significantly more immobility in the FST versus all other groups, indicating depressive-like behavior. No differences between groups were observed in the other behavioral measures. These results indicate that aCRS elicits depressive-like behavioral characteristics in adult female rats without increasing anxiety-like behaviors. (PsycINFO Database Record
IntroductionDepression is a mood disorder often predicated by childhood or adolescent stress. Many rodent models of depression utilize neonatal stress to elicit behavioral changes that persist in adulthood, but the influence of adolescent stress on depressive‐like behaviors has not been widely reported. Additionally, reports correlating adolescent stress with adult depressive‐like behaviors have largely neglected to evaluate the effect of common antidepressants.ObjectiveThe objective of this study is to develop and validate an adolescent chronic restraint stress (aCRS) model of depression in adult female rats.MethodsPilot For the pilot study, 12 adolescent female Sprague‐Dawley rats were shipped post‐natal day (PND) 25–30 and habituated to the colony room for 7 days prior to the experiment. Rats were randomly assigned to Not Restrained (NR, n=6) or Restrained (R, n=6) groups. Beginning PND 36±4, R rats were restrained at random times for 60 min/day for 12 consecutive days. Behavioral testing commenced PND 65±4 and included elevated plus maze (EPM), locomotor activity (LCA), and FST. Experiment 1 Experiment 1 was modified from the pilot in that 27 rats were shipped PND 19, 22, or 23, and randomly assigned to Not Restrained‐Saline (NRSAL, n=6), Restrained‐Saline (RSAL, n=7), Restrained‐Desipramine (RDES, n=7), or Restrained‐Fluoxetine (RFLX, n=7). Restraint began PND 33±1 and lasted 14 consecutive days. Beginning PND 47±1, all animals were given daily subcutaneous injections of 5 mg/kg fluoxetine or desipramine in saline solution, or saline, for 14 days. Behavioral testing commenced PND 61±1 and was preceded by a blood collection that served as a stress challenge. Experiment 2 Experiment 2 was modified from experiment 1 in that 20 rats were shipped PND 19 or 22, group sizes were each n=5, behavioral testing commenced PND 61±1 and did not include EPM. No stress challenge or blood collections were performed. Experiment 3 Experiment 3 was modified from experiment 2 in that 16 rats were shipped PND 23, groups were NRSAL (n=5), RSAL (n=6), or RDES (n=5), restraint began PND 35±1, the final restraint session was followed by 7 days of no stress, injections began PND 56±1, and behavioral testing commenced PND 71±1 and included EPM.ResultsPilot Immobility in the FST was significantly greater in R vs NR rats. EPM and LCA were not different. Experiment 1 Immobility was significantly greater in RSAL vs NRSAL rats due to significantly less swimming. Compared to RSAL, immobility was significantly greater in RDES, but not RFLX rats. EPM and LCA were not different. Experiment 2 Immobility was significantly greater in RSAL vs NRSAL rats due to significantly less swimming and climbing. Compared to RSAL, immobility was significantly less in RDES, but not RFLX rats, due to significantly greater swimming. Both RDES and RFLX showed significantly less locomotor activity vs saline groups, but NRSAL and RSAL were not different from each other. EPM was not different. Experiment 3 Immobility was significantly greater in RSAL vs NRSAL rats due to significantly less swimming. Compared to RSAL, immobility was significantly less in RDES rats due to significantly greater swimming. EPM and LCA were not different.ConclusionThe persistent depressive‐like behaviors elicited by aCRS are reversible with chronic desipramine, but not fluoxetine.Support or Funding InformationMercer University
IntroductionDepression is a mood disorder that disproportionately affects women, and is often predicated by childhood or adolescent stress. Symptoms of depression include persistent sadness and cognitive impairment, which have been correlated with low serum brain‐derived neurotrophic factor (BDNF), and with decreased hippocampal (HIP) volume. Our lab has previously used a novel method of adolescent chronic restraint stress (aCRS) to elicit robust depressive‐like behaviors in freely cycling female Sprague‐Dawley rats. Chronic desipramine (DES), a tricyclic antidepressant, decreased depressive‐like behaviors in aCRS rats. To estimate estrus cycle at time of behavioral testing, we removed and weighed the uteri (UTI) immediately after sacrifice, and found no differences among groups.ObjectiveThe objective of this study was to evaluate behaviors and biomarkers in female rats exposed to aCRS, DES, or aCRS+DES.Methods25adolescent female Sprague‐Dawley rats (Charles River, Kingston, NY) arrived post‐natal day (PND) 26 and habituated to the colony room for 7 days prior to the experiment. Rats were randomly assigned to Not Restrained‐Saline (NRSAL, n=6), Not Restrained Desipramine (NRDES, n=6), Restrained‐Saline (RSAL, n=6), or Restrained‐Desipramine (RDES, n=7). Beginning PND 34±1RSAL and RDES rats were restrained at random times for 60 mins/day for 14consecutive days. The final restraint session was followed by 7 days of maturation. Beginning PND 55±1, NRSAL and RSAL rats received subcutaneous (SC) saline injections (0.09% NaCl; 1 mL/kg) and NRDES and RDES rats received SC desipramine in saline solution (5 mg/kg, 1 mL/kg) daily for 14consecutive days. Behavioral testing commenced PND 70±1 and included, in order, locomotor activity (LCA), novel object recognition (NOR), and a 5‐minute forced swim test(FST). Fifteen minutes following the FST, the rats were sacrificed via rapid decapitation. Serum from trunk blood was separated using serum separating tubes, and the HIP and uteri (UTI) were harvested and weighed. Serum was evaluated for BDNF with ELISA (Boster Bio, Pleasanton, CA). All measures were evaluated with two‐way ANOVA and Holm‐Sidak post hoc, and inter‐measure relationships were evaluated with Pearson correlation analysis.ResultsNo differences were observed in locomotor activity, HIP weight, or UTI weight among groups.During NOR, RSAL rats showed significantly impaired discrimination between novel and familiar objects than NRSAL rats (p=0.011). NRDES and RDES were not different from NRSAL.In FST, RSAL rats were significantly more immobile than all other groups (p=0.011). Specifically, RSAL vs NRSAL (p=0.002), RSAL vs RDES(p=<0.001), and RSAL vs NRDES (p=0.029). NRDES and RDES were not different from NRSAL.Using Pearson correlation analysis, immobility was positively correlated with serum BDNF (r=0.54; p=0.006). No other significant correlations were observed.ConclusionsThese results indicate that aCRS elicits robust depressive‐like behavior and cognitive impairment in freely cycling female rats, effects which are ameliorated by chronic DES. Additionally, the unexpected relationship observed between serum BDNF and immobility requires further investigation.Support or Funding InformationMercer University
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