Matching Items (5)
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- All Subjects: Chronic Stress
- Creators: Orchinik, Miles
Description
Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind the improvements in hippocampal mediated cognition when chronic stress ends and a post-stress rest period is given. Consequently, the goal of this dissertation is to uncover the mechanisms that allow for spatial ability to improve in the aftermath of chronic stress. In chapter 2, the protein brain derived neurotrophic factor (BDNF) was investigated as a mechanism that allows for spatial ability to show improvements following the end of chronic stress. It was found that decreasing the expression of BDNF in the hippocampus prevented spatial memory improvements following a post-stress rest period. Chapter 3 was performed to determine whether hippocampal CA3 apical dendritic complexity requires BDNF to show improvements following a post-stress rest period, and whether a receptor for BDNF, TrkB, mediates the improvements of spatial ability and dendritic complexity in a temporal manner, i.e. during the rest period only. These experiments showed that decreased hippocampal BDNF expression prevented improvements in dendritic complexity, and administration of a TrkB antagonist during the rest period also prevented the improvements in spatial ability and dendritic complexity. In chapter 4, the role of the GABAergic system on spatial ability following chronic stress and a post-stress rest period was investigated. Following chronic stress, it was found that male rats showed impairments on the acquisition phase of the RAWM and this correlated with limbic glutamic acid decarboxylase, a marker for GABA. In chapter 5, a transgenic mouse that expresses a permanent marker on all GABAergic interneurons was used to assess the effects of chronic stress and a post-stress rest period on hippocampal GABAergic neurons. While no changes were found on the total number of GABAergic interneurons, specific subtypes of GABAergic interneurons were affected by stressor manipulations. Collectively, these studies reveal some mechanisms behind the plasticity seen in the hippocampus in response to a post-stress rest period.
ContributorsOrtiz, J. Bryce (Author) / Conrad, Cheryl D. (Thesis advisor) / Newbern, Jason M. (Committee member) / Orchinik, Miles (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2018
Description
Monoamine neurotransmitters (e.g., serotonin, norepinephrine, and dopamine) are powerful modulators of mood and cognitive function in health and disease. We have been investigating the modulation of monoamine clearance in select brain regions via organic cation transporters (OCTs), a family of nonselective monoamine transporters. OCTs are thought to complement the actions of selective monoamine transporters in the brain by helping to clear monoamines from the extracellular space; thus, assisting to terminate the monoamine signal. Of particular interest, stress hormones (corticosterone; CORT) inhibit OCT3-mediated transport of monoamine, to putatively lead to prolonged monoamine signaling. It has been demonstrated that stress levels of CORT block OCT3 transport in the rat hypothalamus, an effect that likely underlies the rapid, stress-induced increase in local monoamines. We examined the effect of chronic variable stress (CVS) on the development of mood disorders and OCT3 expression in limbic and hypothalamic regions of the rat brain. Animals subjected to CVS (14-days with random stressor exposure two times/day) showed reduced body weight gain, indicating that CVS was perceived as stressful. However, behavioral tests of anxiety and depressive-like behaviors in rats showed no group differences. Although there were no behavioral effects of stress, molecular analysis revealed that there were stress-related changes in OCT3 protein expression. In situ hybridization data confirmed that OCT3 mRNA is expressed in the hippocampus, amygdala, and hypothalamus. Analysis of Western blot data by two-way ANOVA revealed a significant treatment effect on OCT3 protein levels, with a significant decrease in OCT3 protein in the amygdala and hippocampus in CVS rats, compared to controls. These data suggest an important role for CORT sensitive OCT3 in the reduction of monoamine clearance during stress.
ContributorsBoyll, Piper Savannah (Author) / Orchinik, Miles (Thesis director) / Conrad, Cheryl (Committee member) / Talboom, Joshua (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The stress response facilitates our ability to deal effectively with threatening situations, but exposure to severe or chronic stressors can lead to undesirable neural, physiological, and behavioral outcomes. Chronic stress is associated with structural changes in the rat hippocampus, with corresponding deficits in learning and memory. Recent studies have uncovered an inherent neuroplasticity that allows the hippocampus to recover from these stress-induced neural changes. Underlying mechanisms likely involve several different cellular and molecular pathways. In order to gain a more comprehensive understanding of these pathways, we investigated differences in protein expression throughout the timeline of chronic stress and recovery. Male Sprague-Dawley rats were randomly assigned to chronic restraint stress for 6hr/d/10d or 6hr/d/21d, stress for 6hr/d/21d followed by a recovery period of no stress for 10 or 21 days, or a control group. The proteome from the hippocampus of these rats was sequenced using liquid chromatography tandem mass spectrometry (LC-MS/MS) and analyzed. We hypothesized that chronic stress alters interneuronal signaling in the hippocampus by enhancing or attenuating the expression of proteins responsible for synaptic plasticity (functional) and neuronal structure (morphology). So far we have found that structural proteins, such as alpha-internexin, homer protein homolog 3, neurofilament light, and vimentin were significantly altered by chronic stress and recovery. In contrast, proteins necessary for or associated with myelination such as 2',3'-cyclic-nucleotide 3'-phosphodiesterase, myelin-associated glycoprotein, myelin basic protein S, and myelin proteolipid protein were significantly downregulated by chronic stress. Collectively, these results will provide a resource for further investigations into the mechanisms of the brain's recovery from chronic stress.
ContributorsKachemov, Marketta Marilyn (Author) / Orchinik, Miles (Thesis director) / Pirrotte, Patrick (Committee member) / Conrad, Cheryl (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Arizona State University and Banner Thunderbird Hospital have partnered to provide pre-med students with an internship at a local emergency department. Students entering into this program will have access to each patient's vital signs, medical imaging, lab tests, and medications. This access presents students with an opportunity to learn about a variety of tools used in the assessment and treatment of emergency room patients. In order to enhance the amount of knowledge students take away from the program, I created a handbook summarizing a variety of diagnostic tests and medications. The first section of the handbook (assessment) is spilt up into the three following categories: vital signs, medical imaging, and lab tests. The second section (treatment) consists of one category, medications. Each section was written with emphasis on basic physiology, and is intended to provide pre-med students with a foundation for building further medical knowledge. Although this handbook was tailored to the information students are most likely to encounter working in Banner Thunderbird Hospital's emergency department, it is still appropriate for any student interested in learning about emergency medicine.
ContributorsBecker, Bryson (Author) / Orchinik, Miles (Thesis director) / Washo-Krupps, Delon (Committee member) / School of Life Sciences (Contributor) / W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Chronic restraint stress leads to apical dendritic retraction in CA3 pyramidal neurons and often no quantifiable changes in CA1 dendritic complexity. When chronic stress ends, a post-stress recovery period results in an enhancement in CA3 dendritic complexity. We investigated the relationship between CA3 and CA1 pyramidal neurons to determine whether dendritic restructuring in CA3 neurons leads to region-specific changes in the dendritic complexity of CA1 neurons. Adult male Sprague-Dawley rats were restrained (wire mesh, 6h/d/21d) and brains were removed soon after restraint ended (Str-Imm) or after a 21d post-stress recovery period (Str-Rec). In addition, BDNF downregulation targeting the CA3 region prevents enhancement in dendritic complexity following recovery in chronically stressed rats, providing robust conditions to investigate the CA3-CA1 relationship. Consequently, rats were infused into the CA3 area with either an AAV vector with a coding sequence against BDNF (shRNA) or a sequence with no known mRNA complements (Scr). Apical and basal dendritic complexity of CA3 and CA1 was quantified by counting total dendritic bifurcations and dendritic intersections using the Sholl analysis (20 µm distances from soma). Please note that the quantification of the CA3 dendritic arbors was not part of this thesis project. The outcome of that investigation revealed that apical CA3 dendritic retraction was found in Str-Imm-Scr and Str-Rec-shRNA. For the CA1 apical area, gross dendritic bifurcation differences were not detected, but the Sholl quantification revealed regionally-enhanced dendritic complexity that varied by distance from the soma at the distal apical dendrites (Str-Imm-Scr) and proximal basal dendrites (Str-Rec-shRNA). For the latter, significant increases in basal branch points were detected with total branch point quantification method. Moreover, a correlation using all groups revealed a significant inverse relationship between CA3 apical dendritic complexity and CA1 basal dendritic complexity. The results demonstrate that chronic stress-induced CA3 apical dendritic retraction may relate to region-specific changes in CA1 dendritic complexity. The inability of past studies to detect changes in CA1 dendritic complexity may be due to the shortcoming of gross dendritic arbor measures in accounting for subtle region-specific alterations. To address this, the current study included a cohort with BDNF downregulated in the CA3 region. Overall, this suggests that decreased levels of BDNF in the hippocampus provide robust conditions in which changes to CA1 dendritic complexity can be detected.
ContributorsDaas, Eshaan Jatin (Author) / Conrad, Cheryl (Thesis director) / Orchinik, Miles (Committee member) / Ortiz, J. Bryce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12