The intracellular free Ca2+ concentration of CMS neurons is highly regulated. Small changes in the cytosolic Ca2+ concentration and different patterns of Ca2+ transients are used by CMS neurons to mediate important functional and developmental processes. Increases in the cytosolic Ca2+ concentration can arise from entry of extracellular Ca2+ through ion channels in the plasma membrane or via the release of Ca2+ from intracellular stores. Both entry of extracellular Ca2+ and release of Ca2* from intracellular stores are directly coupled to neuronal function. For the development of acute and chronic degenerative diseases reducing the viability and function of CNS neurons several studies indicate that both changes in intracellular second messenger concentration and pathological increases in the intracellular Ca2+ concentration promote pathogenesis. The present application will test the two-pronged hypothesis that Ca2+ signaling of CNS neurons is functionally regulated by associated proteins of intracellular Ca2+ channels and that control of their expression and function represents a novel target for CNS neuroprotection. The proposed experiments designed to test this hypothesis will investigate the functional mechanism underlying this interaction under experimentally induced disease conditions in models of acute and chronic degenerative CNS diseases.
The specific aims of this proposal are to determine a) changes in the expression and localization, b) function and c) modulation of these proteins based on therapeutic intervention studies in pre-clinical models of AD and age-related cognitive impairment. The overall goal of the study is to identify a novel mechanism of neuroprotection and determine its potential as a strategy for neuroprotective therapies targeting the aging brain and age-related neurodegenerative diseases such as Alzheimer's disease. This therapy approach will have the potential to be both preventative and therapeutic in nature and to complement existing treatment designs and rationales. Thus, potential new targets for treating those devastating conditions affecting the aging population may be identified.
| Izurieta Munoz, Haydee; Gonzales, Eric B; Sumien, Nathalie (2018) Effects of creatine supplementation on nociception in young male and female mice. Pharmacol Rep 70:316-321 |
| Mock, J Thomas; Knight, Sherilynn G; Vann, Philip H et al. (2018) Gait Analyses in Mice: Effects of Age and Glutathione Deficiency. Aging Dis 9:634-646 |
| Grillo, Michael A; Grillo, Stephanie L; Gerdes, Bryan C et al. (2018) Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin. Mol Neurobiol : |
| Kaja, Simon; Payne, Andrew J; Naumchuk, Yuliya et al. (2017) Quantification of Lactate Dehydrogenase for Cell Viability Testing Using Cell Lines and Primary Cultured Astrocytes. Curr Protoc Toxicol 72:2.26.1-2.26.10 |
| Shetty, Ritu A; Rutledge, Margaret A; Forster, Michael J (2017) Retrograde conditioning of place preference and motor activity with cocaine in mice. Psychopharmacology (Berl) 234:515-522 |
| Engler-Chiurazzi, E B; Brown, C M; Povroznik, J M et al. (2017) Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury. Prog Neurobiol 157:188-211 |
| Engler-Chiurazzi, Elizabeth B; Covey, Douglas F; Simpkins, James W (2017) A novel mechanism of non-feminizing estrogens in neuroprotection. Exp Gerontol 94:99-102 |
| Mock, J Thomas; Chaudhari, Kiran; Sidhu, Akram et al. (2017) The influence of vitamins E and C and exercise on brain aging. Exp Gerontol 94:69-72 |
| Russell, Ashley E; Doll, Danielle N; Sarkar, Saumyendra N et al. (2016) TNF-? and Beyond: Rapid Mitochondrial Dysfunction Mediates TNF-?-Induced Neurotoxicity. J Clin Cell Immunol 7: |
| Richter, Frank; Koulen, Peter; Kaja, Simon (2016) N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release. Sci Rep 6:23481 |
Showing the most recent 10 out of 173 publications
