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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

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.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Olive, M. Foster (Committee member) / Taylor, Sara (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Sports related concussions, or mild traumatic brain injuries (mTBI), have recently increased in prevalence, and thus gained a great deal of recognition from the public and the media. While the acute symptoms associated with concussions are well known, which include headaches, dizziness, vomiting, and fatigue, recent research has indicated that

Sports related concussions, or mild traumatic brain injuries (mTBI), have recently increased in prevalence, and thus gained a great deal of recognition from the public and the media. While the acute symptoms associated with concussions are well known, which include headaches, dizziness, vomiting, and fatigue, recent research has indicated that there can be severe chronic consequences of multiple conditions. Most notably, a disease called Chronic Traumatic Encephalopathy (CTE) has been linked to multiple mTBIs, which produces symptoms similar to Alzheimer's disease and dementia, in addition to personality changes, increased suicidality, and in some cases death. This knowledge has led the NFL to take steps to protect their players, and increase both the understanding and awareness of the problems associated with multiple concussions. This comes with many problems, however, as players and fans alike are quick to resist any type of change to the rules or policies present in football, in fear that it may damage the integrity of the game. The NFL is thus forced into a difficult position, and must balance public opinion and player safety. There are things that can be done, however, that do not threaten the game itself, such as investing in concussion research and safety equipment design that will more effectively protect the brain from concussions.
ContributorsAiello, Mimi Elizabeth (Author) / Olive, M. Foster (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Camp, Bryan (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2013-05
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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

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.
ContributorsAcuna, Amanda Marie (Author) / Conrad, Cheryl (Thesis director) / Corbin, William (Committee member) / Olive, M. Foster (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12