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The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk
The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk
All ETDs from UAB
Klotho is an anti-aging protein that when upregulated, extends lifespan and enhances cognition. Klotho knockout mice age prematurely and die by ~8 weeks of life after developing cognitive impairment. Klotho function outside of the brain is well established but the protein’s action within the brain remains unknown. As klotho regulates peripheral stem cell populations, I sought to determine whether klotho contributes to cognition through a role in the maintenance of the adult hippocampal neurogenic niche. I examined adult mouse neurogenesis using global klotho-deficiency or global klotho overexpression models. Klotho knockout brains show reduced progenitor proliferation and granule cell production while …
Modeling Mild And Repeated Mild Traumatic Brain Injury Induced Functional And Pathophysiological Alterations, Jessica Nicole Nichols
Modeling Mild And Repeated Mild Traumatic Brain Injury Induced Functional And Pathophysiological Alterations, Jessica Nicole Nichols
All ETDs from UAB
Mild traumatic brain injury (mTBI) is a major health concern and accounts for over 75% of the 2.5 million brain injuries reported annually in the United States. Afflicted individuals typically experience a broad spectrum of physical, cognitive, and neuropsychological symptoms. Repeated mTBIs (rmTBIs) can further exacerbate these physiological alterations and negatively impact patient quality of life. Currently, there are no therapeutic agents that have successfully navigated clinical trials to be shown efficacious despite mounds of preclinical evidence suggesting to the contrary. This lack of translation exposes the dire need to design, characterize, and implement better and more relevant model systems …
Transcriptional Dysregulation In Interneurons Causes Altered Modulation Of Hippocampal Synaptic Transmission And Circuit Function By The Dopamine System, Lillian J. Brady
Transcriptional Dysregulation In Interneurons Causes Altered Modulation Of Hippocampal Synaptic Transmission And Circuit Function By The Dopamine System, Lillian J. Brady
All ETDs from UAB
Genetic deletion of the transcriptional coactivator PGC-1α leads to transcriptional dysregulation in interneurons, and transcriptional dysregulation in interneurons lead to changes in hippocampal synaptic transmission and circuit function. Hippocampal circuit activity and synaptic transmission alterations have implications for symptoms of cognitive impairment in neurological disorders like schizophrenia. Modulation of dopamine receptor activity through pharmacologic application of haloperidol and the specific dopamine D4 receptor antagonist L-745,870 in PGC-1α-/- mice leads to altered effects on inhibitory/excitatory synaptic transmission balance, circuit function, and innate hippocampal dependent nesting behavior. These are key aspects underlying hippocampus dependent cognitive impairment. Specifically, bath application of haloperidol restores …