| dc.identifier.uri | http://hdl.handle.net/11401/77622 | |
| 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.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Major Depressive Disorder (MDD) is a leading cause of disease burden in the world. Improved understanding and treatment of MDD and related mood and stress disorders such as bipolar disorder (BD), anxiety and post-traumatic stress disorder (PTSD) are critical public health priorities. Contemporary theories of the neurological basis of MDD place emphasis on the intracellular and structural changes in neurons, but more recent animal models and postmortem human studies have correlated glial cell loss with MDD development. The glial cell-types involved, the mechanisms underlying the loss, and whether it is causal in MDD development are unknown. Glial cells expressing the NG2 chondroitin sulphate proteoglycan (NG2+ glia) constitute a lineage distinct from astrocytes, myelinating oligodendrocytes, and microglia. NG2+ glia function as myelin-forming cell progenitors but remain abundant throughout the adult brain, suggesting roles in normal brain function. Here, we show using mouse models of depression and tissue samples from patients with MDD and BD, that NG2+ cell density is reduced in areas critical in MDD development. Moreover, depletion of NG2+ glia using conditional genetic strategies in these areas induces depressive-like behavioral, cellular, molecular, and physiological changes similar to those observed in animal models of depression and patients with MDD. Finally, we identify NG2+ glia-derived growth factors and neurotrophins differentially regulated after chronic social defeat that may drive the deficits in neuronal and astrocyte function. Our findings reveal that NG2+ glia play essential functions in maintaining normal adult brain function and that dysfunction of these roles and the ultimate loss of NG2+ glia are implicated in the pathophysiology of MDD and related disorders, thus constituting a new target for understanding and therapeutically managing MDD. We anticipate our study to lead future investigations in further elaborating the mechanistic roles of NG2+ glia in MDD and other psychiatric disorders. | |
| dcterms.available | 2017-09-20T16:53:03Z | |
| dcterms.contributor | Aguirre, Adan | en_US |
| dcterms.contributor | White, Thomas | en_US |
| dcterms.contributor | Robinson, John | en_US |
| dcterms.contributor | Colognato, Holly | en_US |
| dcterms.contributor | Ge, Shaoyu | en_US |
| dcterms.contributor | Russo, Scott. | en_US |
| dcterms.creator | Birey, Fikri | |
| dcterms.dateAccepted | 2017-09-20T16:53:03Z | |
| dcterms.dateSubmitted | 2017-09-20T16:53:03Z | |
| dcterms.description | Department of Genetics. | en_US |
| dcterms.extent | 142 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/77622 | |
| dcterms.issued | 2015-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:53:03Z (GMT). No. of bitstreams: 1
Birey_grad.sunysb_0771E_12108.pdf: 5624719 bytes, checksum: ef0f7e121bdaab84fe6c1b6f51ee9b62 (MD5)
Previous issue date: 2014 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Neurosciences | |
| dcterms.title | The Loss of NG2+ Glia-Mediated CNS Homeostasis in the Pathophysiology of Depression | |
| dcterms.type | Dissertation | |
