Depression is a psychiatric disorder where disturbance of mood is a prominent feature. Although the etiology of depression is unknown, alterations in serotonergic and noradrenergic function are implicated in the condition. The present Conte Center Grant proposes to examine depression from perspectives of functional imaging, morphometrics, and pharmacological interventions in humans, as well as though mouse genetic, molecular, biochemical, behavioral, and electrophysiological models of depression. The overall objective of the present proposal is to show how the norepinephrine (NE) and serotonin (5-HT) systems are interdependent in the development and amelioration of symptoms of depression, and to reveal novel mechanisms that contribute to the disorder. There are three major Aims.
AIM 1 : The roles in depression of the NE transporter, 5-HT transporter, and vesicular monoamine transporter 2 will be investigated. Effects of antidepressants on monoamine and metabolite levels in various brain regions will be studied. Molecular fingerprinting of signal transduction pathways will be used to analyze effects of genotype and antidepressant treatment.
AIM 2 : The role in depression of glycogen synthase kinase-3beta (GSK3b) will be analyzed. Mice will be developed that have GSK3b selectively deleted in the CNS. Animals will be evaluated according to behavioral, neurotransmitter, and signal transduction responses to antidepressants.
AIM 3 : Mice will be made that bear the same polymorphisms in tryptophan hydroxylase 2 (Tph2) found in human depressed patients. Mutants will be examined according to behavioral, neurotransmitter, and signal transduction responses to antidepressants and electroconvulsive therapy.
|Petyuk, Vladislav A; Chang, Rui; Ramirez-Restrepo, Manuel et al. (2018) The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target. Brain 141:2721-2739|
|Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384|
|Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738|
|Karch, Celeste M; Ezerskiy, Lubov A; Bertelsen, Sarah et al. (2016) Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One 11:e0148717|
|Mez, Jesse; Mukherjee, Shubhabrata; Thornton, Timothy et al. (2016) The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable. Neurobiol Aging 41:115-121|
|Ridge, Perry G; Hoyt, Kaitlyn B; Boehme, Kevin et al. (2016) Assessment of the genetic variance of late-onset Alzheimer's disease. Neurobiol Aging 41:200.e13-200.e20|
|Hohman, Timothy J; Bush, William S; Jiang, Lan et al. (2016) Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium. Neurobiol Aging 38:141-150|
|Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M et al. (2016) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21:108-17|
|Jacobsen, Jacob Pr; Rudder, Meghan L; Roberts, Wendy et al. (2016) SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept. Neuropsychopharmacology 41:2324-34|
|Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-129|
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