{"id":11,"date":"2024-07-11T18:19:33","date_gmt":"2024-07-11T18:19:33","guid":{"rendered":"https:\/\/labs.uthscsa.edu\/oconnor\/?page_id=11"},"modified":"2024-12-17T16:50:56","modified_gmt":"2024-12-17T16:50:56","slug":"research","status":"publish","type":"page","link":"https:\/\/labs.uthscsa.edu\/oconnor\/research\/","title":{"rendered":"Research"},"content":{"rendered":"

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Research in Progress<\/h2>\n

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Does BDNF mediate resilience to inflammation-induced depression and cognitive impairment? (VA Merit Award)<\/h5>[vc_column_text css=””]The U.S. Veteran population experiences high rates of depression and elevated suicide risk, highlighting the need to identify genetic and neural mechanisms underlying depression. Reduced brain-derived neurotrophic factor (BDNF) is associated with depression and impaired antidepressant response. However, the mechanisms linking BDNF deficiency to depression remain unclear.<\/p>\n

A common human BDNF polymorphism (Val66Met) reduces BDNF levels, making it highly relevant for understanding gene-environment interactions, such as inflammation and stress, in depression. Preliminary data suggest BDNF negatively regulates microglial activation, and its disruption sensitizes mice to inflammation- or stress-induced depressive behaviors.<\/p>\n

Using mouse models and human postmortem analyses, this project aims to determine how BDNF deficiency drives prefrontal cortex (PFC)-dependent depressive behaviors through increased microglial reactivity and neurotoxic tryptophan metabolism. Findings may lead to novel diagnostic and therapeutic approaches for vulnerable patients.[\/vc_column_text][\/vc_column][vc_column width=”1\/3″] \n \n \n <\/i>\n <\/i>\n <\/span>

Publications<\/h4>\n <\/a>[\/vc_column][\/vc_row][vc_row full_width=”stretch_row”][vc_column width=”1\/4″][vc_single_image image=”133″ img_size=”large” add_caption=”yes” css=””][\/vc_column][vc_column width=”5\/12″]
Family Health Patterns Project (Multi-PI Collaboration Supported by NIH R01)<\/h5>[vc_column_text css=””]Individuals with a family history of alcoholism (FH+) are 4 to 8 times more likely to develop alcohol use disorder (AUD) than those without such histories. The Family Health Patterns Project explores risk-related phenotypes in FH+ young adults, revealing links between early life adversity (ELA) and (a) blunted stress reactivity, (b) increased antisocial tendencies, (c) poor affect regulation, and (d) impaired cognitive performance. Neuroimaging studies show diffusivity changes in frontal white matter tracts, indicating impaired myelination and axon damage, likely contributing to these behavioral vulnerabilities.<\/p>\n

We investigate a model where family history and ELA lead to blunted HPA stress reactivity, immunologic dysregulation, and increased immunoreactivity, impairing frontal white matter development. This disruption reduces communication with the prefrontal cortex, driving antisocial behaviors, poor affect regulation, and cognitive deficits, increasing AUD risk. To test this, we will analyze genome-wide immunologic gene expression, white blood cell immunoreactivity, and white matter integrity, examining their relationships with ELA and phenotypic risks in FH+ and FH\u2013 young adults.[\/vc_column_text][\/vc_column][\/vc_row][vc_row full_width=”stretch_row”][vc_column width=”1\/4″][vc_single_image image=”135″ img_size=”large” add_caption=”yes” css=””][\/vc_column][vc_column width=”5\/12″]

Nutritional Mechanism to Enhance Exercise Benefits on Aging Cognition and Fatigue (Supported by the Morrison Trust)<\/h5>[vc_column_text css=””]Cognitive decline and fatigue are common age-related symptoms with no specific treatments. Our research suggests that oxidative metabolism of tryptophan via the kynurenine pathway contributes to these symptoms. Deleting key enzymes for kynurenine metabolism prevents cognitive decline in old mice, while dietary leucine supplementation increases voluntary wheel running by nearly 3x, indicating reduced fatigue.<\/p>\n

We hypothesize that leucine exerts neuroprotective effects in aging through two mechanisms: 1) competing with tryptophan\/kynurenine for brain transport and 2) stimulating PGC-1\u03b1-driven oxidative kynurenine metabolism in skeletal muscle, reducing brain kynurenine metabolism and neuroinflammation.[\/vc_column_text][\/vc_column][\/vc_row][vc_row full_width=”stretch_row”][vc_column width=”2\/3″][vc_column_text css=””]<\/p>\n

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Great things are coming soon.<\/h2>\n

[\/vc_column_text][\/vc_column][\/vc_row][vc_row full_width=”stretch_row”][vc_column width=”1\/4″][vc_single_image image=”31″ img_size=”large” css=””][\/vc_column][vc_column width=”5\/12″]

Look here for more research information soon.<\/h3><\/a>[vc_column_text css=””][\/vc_column_text][\/vc_column][\/vc_row]<\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

[vc_row full_width=”stretch_row”][vc_column width=”2\/3″][vc_column_text css=””] Research in Progress [\/vc_column_text][\/vc_column][\/vc_row][vc_row full_width=”stretch_row”][vc_column width=”1\/4″][vc_single_image image=”134″ img_size=”large” add_caption=”yes” css=””][\/vc_column][vc_column width=”5\/12″][vc_column_text css=””]The U.S. Veteran population experiences high rates of depression and elevated suicide risk, highlighting the need to identify genetic and neural mechanisms underlying depression. Reduced brain-derived neurotrophic factor (BDNF) is associated with depression and impaired antidepressant response. However, the mechanisms […]<\/p>\n","protected":false},"author":94,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-11","page","type-page","status-publish","hentry"],"yoast_head":"\nResearch - Dr. Jason O'Connor Lab<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/labs.uthscsa.edu\/oconnor\/research\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Research - Dr. Jason O'Connor Lab\" \/>\n<meta property=\"og:description\" content=\"[vc_row full_width=”stretch_row”][vc_column width=”2\/3″][vc_column_text css=””] Research in Progress [\/vc_column_text][\/vc_column][\/vc_row][vc_row full_width=”stretch_row”][vc_column width=”1\/4″][vc_single_image image=”134″ img_size=”large” add_caption=”yes” css=””][\/vc_column][vc_column width=”5\/12″][vc_column_text css=””]The U.S. Veteran population experiences high rates of depression and elevated suicide risk, highlighting the need to identify genetic and neural mechanisms underlying depression. 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