Neuroscience and Neurobiology Commons^™

Divergence In Neuronal Calcium Dysregulation In Brain Aging And Animal Models Of Ad, Adam Ghoweri

Theses and Dissertations--Pharmacology and Nutritional Sciences

Neuronal calcium dysregulation first garnered attention during the mid-1980’s as a key factor in brain aging, which led to the formulation of the Ca²⁺ hypothesis of brain aging and dementia. Indeed, many Ca²⁺-dependent cellular processes that change with age, including an increase in the afterhyperpolarization, a decrease in long-term potentiation, an increased susceptibility to long-term depression, and a reduction in short-term synaptic plasticity, have been identified. It was later determined that increased intracellular Ca²⁺ with age was due to increased Ca²⁺ channel density, elevated release from intracellular Ca²⁺ stores, and decreased Ca²⁺ buffering …

The Role Of Astrocytic Calcineurin Activation And Downstream Signaling In Neurodegenerative Diseases, Melanie M. Pleiss

Theses and Dissertations--Pharmacology and Nutritional Sciences

Calcineurin (CN) is a calcium (Ca²⁺)-sensitive serine/threonine protein phosphatase that plays a significant role in several cell signaling pathways, and has been implicated in many neurodegenerative diseases including Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID). Although normally found in neurons, CN also appears at high levels in activated astrocytes under conditions of injury and disease. To elucidate the role of astrocytic calcineurin signaling in neurodegenerative diseases, our lab has used primary rat astrocytes, transgenic and diet-induced mouse models of dementia, and human tissue biospecimens from confirmed AD and VCID cases.

To better understand mechanisms for …