Matching Items (6)

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Does an extended washout period of six weeks following the end of chronic stress continue the benefits on spatial learning and memory?

Description

Chronic stress often leads to cognitive deficits, especially within the spatial memory domain mediated by the hippocampus. When chronic stress ends and a no-stress period ensues (i.e., washout, WO), spatial

Chronic stress often leads to cognitive deficits, especially within the spatial memory domain mediated by the hippocampus. When chronic stress ends and a no-stress period ensues (i.e., washout, WO), spatial ability improves, which can be better than non-stressed controls (CON). The WO period is often the same duration as the chronic stress paradigm. Given the potential benefit of a post-stress WO period on cognition, it is important to investigate whether this potential benefit of a post-stress WO period has long-lasting effects. In this project, chronic restraint (6hr/d/21d) in Sprague-Dawley rats was used, as it is the minimum duration necessary to observe spatial memory deficits. Two durations of post-stress WO were used following the end of chronic restraint, 3 weeks (STR-WO3) and 6 weeks (STR-WO6). Immediately after chronic stress (STR-IMM) or the WO periods, rats were tested on various cognitive tests. We corroborated past studies that chronic stress impaired spatial memory (STR-IMM vs CON). Interestingly, STR-WO3 and STR-WO6 failed to demonstrate improved spatial memory on a radial arm water maze task, performing similarly as STR-IMM. Performance outcomes were unlikely from differences in anxiety or motivation because rats from all conditions performed similarly on an open field task and on a simple object recognition paradigm, respectively. However, performance on object placement was unusual in that very few rats explored, suggesting some degree of anxiety or fear in all groups. One possible interpretation of the unusual results of the 3 week washout group may be attributed to the different spatial memory tasks used across studies or external factors from the study. Further exploration of these other factors led to the conclusion that they did not play a role and the STR-WO3 RAWM data were anomalous to other studies. This suggests that a washout period following chronic stress may not be fully understood.

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Agent

Created

Date Created
  • 2017-05

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Spatial Memory Impairments as a Function of Increasing Age in Pet Dogs

Description

Previous research pertaining to dog memory and cognition has been confined mainly to samples of colony dogs and therefore can be hard to generalize to a larger population of pet

Previous research pertaining to dog memory and cognition has been confined mainly to samples of colony dogs and therefore can be hard to generalize to a larger population of pet dogs and varying breeds. The present study focused entirely on pet dogs of many different breeds, rather than colony or laboratory animals for the purposes of accessibility, affordability, and novelty. Methods: We presented the dogs with a memory task in the form of a game in which the dogs chose to search for food at one of two locations at varying delay intervals, with a maximum time limit of one hour per dog. We expected our data to show a significant decrease in memory capacity and an increase in error rates among older dogs as compared to younger dogs; these results would allow us to conclude that it is likely many dogs, much like humans, experience various cognitive deficits as a function of increasing age. Results: Using one-factor ANOVA and linear and curvilinear regression analyses, we examined the relationship between the independent variable, age (individual dog ages as well as three generalized age categories), and three dependent variables. The dependent variables were: (a) percentage of correct choices at a 60 second delay interval, (b) maximum delay interval attempted (MDIA), and (c) the maximum delay interval that was completed above chance level (50%) (MDAC). We found significant results to support our hypotheses that aged dogs show spatial memory and cognitive deficits in comparison with young and middle-aged dogs, and that age can be considered a marginally significant predictor of spatial memory capacity.

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Agent

Created

Date Created
  • 2018-12

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Unpredictable, intermittent, chronic stress may increase dendritic complexity of short shaft hippocampal neurons

Description

Major Depressive Disorder (MDD) affects over 300 million people worldwide, with the hippocampus showing decreased volume and activity in patients with MDD. The current study investigated whether a novel preclinical

Major Depressive Disorder (MDD) affects over 300 million people worldwide, with the hippocampus showing decreased volume and activity in patients with MDD. The current study investigated whether a novel preclinical model of depression, unpredictable intermittent restraint (UIR), would decrease hippocampal neuronal dendritic complexity. Adult Sprague Dawley rats (24 male, 24 female) were equally divided into 4 groups: control males (CON-M), UIR males (UIR-M), control females (CON-F) and UIR females (UIR-F). UIR groups received restraint and shaking on an orbital shaker on a randomized schedule for 30 or 60 minutes/day for two to six days in a row for 26 days (21 total UIR days) before behavioral testing commenced. UIR continued and was interspersed between behavioral test days. At the end of behavioral testing, brains were processed. The behavior is published and not part of my honor’s thesis; my contribution involved quantifying and analyzing neurons in the hippocampus. Several neuronal types are found in the CA3 subregion of the hippocampus and I focused on short shaft (SS) neurons, which show different sensitivities to stress than the more common long shaft (LS) variety. Brains sections were mounted to slides and Golgi stained. SS neurons were drawn using a microscope with camera lucida attachment and quantified using the number of bifurcations and dendritic intersections as metrics for dendritic complexity in the apical and basal areas separately. The hypothesis that SS neurons in the CA3 region of the hippocampus would exhibit apical dendritic simplification in both sexes after UIR was not supported by our findings. In contrast, following UIR, SS apical dendrites were more complex in both sexes compared to controls. Although unexpected, we believe that the UIR paradigm was an effective stressor, robust enough to illicit neuronal adaptations. It appears that the time from the end of UIR to when the brain tissue was collected, or the post-stress recovery period, and/or repeated behavioral testing may have played a role in the observed increased neuronal complexity. Future studies are needed to parse out these potential effects.

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Created

Date Created
  • 2020-12

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Chronic unpredictable intermittent restraint stress disrupts hippocampal-dependent spatial memory in male, but not female rats

Description

The present series of studies examined whether a novel implementation of an

intermittent restraint (IR) chronic stress paradigm could be used to investigate hippocampal-dependent spatial ability in both sexes. In experiments

The present series of studies examined whether a novel implementation of an

intermittent restraint (IR) chronic stress paradigm could be used to investigate hippocampal-dependent spatial ability in both sexes. In experiments 1 and 2, Sprague- Dawley male rats were used to identify the optimal IR parameters to assess spatial ability. For IR, rats were restrained for 2 or 6hrs/day (IR2, IR6, respectively) for five days and then given two days off, a process that was repeated for three weeks and compared to rats restrained for 6hrs/d for each day (DR6) and non-stressed controls (CON). Spatial memory was tested on the radial arm water maze (RAWM), object placement (OP), novel object recognition (NOR) and Y-maze. The results for the first two experiments revealed that IR6, but not IR2, was effective in impairing spatial memory in male rats and that task order impacted performance. In experiment 3, an extended IR paradigm for six weeks was implemented before spatial memory testing commenced in male and female rats (IR- M, IR-F). Unexpectedly, an extended IR paradigm failed to impair spatial memory in either males or females, suggesting that when extended, the IR paradigm may have become predictable. In experiment 4, an unpredictable IR (UIR) paradigm was implemented, in which restraint duration (30 or 60-min) combined with orbital shaking, time of day, and the days off from UIR were varied. UIR impaired spatial memory in males, but not females. Together with other reports, these findings support the interpretation that chronic stress negatively impairs hippocampal-dependent function in males, but not females, and that females appear to be resilient to spatial memory deficits in the face of chronic stress.

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Agent

Created

Date Created
  • 2019

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On the cognitive impact of endogenous and exogenous hormone exposures across the lifespan

Description

Women are exposed to numerous endogenous and exogenous hormones across the lifespan. In the last several decades, the prescription of novel hormonal contraceptives and hormone therapies (HTs) have resulted in

Women are exposed to numerous endogenous and exogenous hormones across the lifespan. In the last several decades, the prescription of novel hormonal contraceptives and hormone therapies (HTs) have resulted in aging women that have a unique hormone exposure history; little is known about the impact of these hormone exposures on short- and long- term brain health. The goal of my dissertation was to understand how lifetime hormone exposures shape the female cognitive phenotype using several innovative approaches, including a new human spatial working memory task, the human radial arm maze (HRAM), and several rodent menopause models with variants of clinically used hormone treatments. Using the HRAM (chapter 2) and established human neuropsychological tests, I determined males outperformed females with high endogenous or exogenous estrogen levels on visuospatial tasks and the spatial working memory HRAM (chapter 3). Evaluating the synthetic estrogen in contraceptives, ethinyl estradiol (EE), I found a high EE dose impaired spatial working memory in ovariectomized (Ovx) rats, medium and high EE doses reduced choline-acetyltransferace-immunoreactive neuron population estimates in the basal forebrain following Ovx (chapter 4), and low EE impaired spatial cognition in ovary-intact rats (chapter 5). Assessing the impact of several clinically-used HTs, I identified a window of opportunity around ovarian follicular depletion outside of which the HT conjugated equine estrogens (CEE) was detrimental to spatial memory (chapter 6), as well as therapeutic potentials for synthetic contraceptive hormones (chapter 9) and bioidentical estradiol (chapter 7) during and after the transition to menopause. Chapter 6 and 7 findings, that estradiol and Ovx benefitted cognition after the menopause transition, but CEE did not, are perhaps due to the negative impact of ovarian-produced, androstenedione-derived estrone; indeed, blocking androstenedione’s conversion to estrone prevented its cognitive impairments (chapter 8). Finally, I determined that EE combined with the popular progestin levonorgestrel benefited spatial memory during the transition to menopause, a profile not seen with estradiol, levonorgestrel, or EE alone (chapter 9). This work identifies several cognitively safe, and enhancing, hormonal treatment options at different time points throughout female aging, revealing promising avenues toward optimizing female health.

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Created

Date Created
  • 2015

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Hippocampal BDNF mediates recovery from chronic stress-induced spatial reference memory deficits

Description

Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal

Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus with adeno- associated viral vectors containing the coding sequence for short interfering (si)RNA directed against BDNF or a scrambled sequence (Scr), with both containing the coding information for green fluorescent protein to aid in anatomical localization. Rats were then chronically restrained (wire mesh, 6h/d/21d) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trial. Rats in the Str-Imm group, regardless of viral vector contents, committed more errors in the spatial reference memory domain than did non-stressed controls. Importantly, the typical improvement in spatial memory following recovery from chronic stress was blocked with the siRNA against BDNF, as Str-Rec-siRNA performed worse on the RAWM compared to the non-stressed controls or Str-Rec-Scr. These effects were specific for the reference memory domain as repeated entry errors that reflect spatial working memory were unaffected by stress condition or viral vector contents. These results demonstrate that hippocampal BDNF is necessary for the recovery from stress-induced hippocampal dependent spatial memory deficits in the reference memory domain.

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Agent

Created

Date Created
  • 2013