| dc.identifier.uri | http://hdl.handle.net/11401/78148 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.type | Dissertation | |
| dcterms.abstract | Chronic stress underlies several disorders, including post-traumatic stress disorder (PTSD), and complicates patient responses to life threatening diseases such as cancer, making this condition an important public health concern. The gene regulatory network integrates several signals, yielding a particular pattern of gene expression. Changes in global gene expression (transcriptome) may provide a reliable measure of the intensity/dosage of stress or drug an animal has experienced as well as distinguish different types of stress or drug experiences. Our studies used RNA sequencing (RNAseq) to analyze the transcriptome in several tissues from rat models of chronic stress and chemotherapy-induced cognitive impairment (CICI or ‘chemobrain’). In part of our research project, several three-week long stress paradigms were developed or adapted: social isolation, chronic variable stress (CVS), social defeat, isolation defeat, grid housing, and chronic shock (CS). RNAseq was used to measure changes in the transcriptome of the adrenal gland following exposure to the two most intense stress protocols, CVS and CS. Candidate genes were selected and validated using real-time PCR in order to identify a small number of genes consistently responsive to stress exposure. This analysis yielded a few genes that were used to compute a stress-sensitive gene expression index (SSGE) uniquely associated with different stress models. Although the stress protocols differed in the intensity and nature of the stressors used, the SSGE index reliably detected every type of stress exposure and provided quantitative differences in chronic stress exposure. The second part of the project assessed the effects of chemotherapy, a combined pharmacological and psychological stressor, on the transcriptome in the brain. ‘Chemobrain’ is well documented in chemotherapy-treated breast cancer patients, but little is known about the mechanisms of this syndrome. We exposed rats to Doxorubicin, Cyclophosphamide, or Paclitaxel, drugs commonly used to treat patients with breast cancer. Three genes involved in hypoxia were upregulated in both the hippocampus and frontal cortex following administration of all drugs, suggesting hypoxia as the underlying mechanism of ‘chemobrain’. These studies will aid in identification of new targets for diagnostics and new therapeutic markers for drug discovery, in order to treat stress-related disorders and ‘chemobrain’. | |
| dcterms.available | 2018-03-22T22:39:08Z | |
| dcterms.contributor | Anderson, Brenda | en_US |
| dcterms.contributor | Parsons, Ryan | en_US |
| dcterms.contributor | McKinnon, David. | en_US |
| dcterms.contributor | Mohanty, Aprajita | en_US |
| dcterms.creator | Jacobson, Moriah L. | |
| dcterms.dateAccepted | 2018-03-22T22:39:08Z | |
| dcterms.dateSubmitted | 2018-03-22T22:39:08Z | |
| dcterms.description | Department of Biopsychology. | en_US |
| dcterms.extent | 255 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/78148 | |
| dcterms.issued | 2017-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2018-03-22T22:39:08Z (GMT). No. of bitstreams: 1
Jacobson_grad.sunysb_0771E_13371.pdf: 4940423 bytes, checksum: e1ffbbf1458254db1198ef8e4f7f4038 (MD5)
Previous issue date: 2017-08-01 | en |
| dcterms.subject | anxiety | |
| dcterms.subject | Behavioral psychology -- Neurosciences. | |
| dcterms.subject | chemotherapy | |
| dcterms.subject | memory | |
| dcterms.subject | ptsd | |
| dcterms.subject | rna sequencing | |
| dcterms.subject | stress | |
| dcterms.title | Novel Animal Models of Chronic Stress and ‘Chemobrain’: Behavioral, Physiological, and Molecular Biomarkers | |
| dcterms.type | Dissertation | |
