Laboratory of Translational Neurobiology
Research in the Laboratory of Translational Neurobiology focuses on studies of interacting genetic and environmental influences on neurodevelopment, and their relevance to the pathogenesis of schizophrenia and Alzheimer’s disease. By collaborating with other laboratories, we are able to combine clinical and pre-clinical approaches to identify novel single-nucleotide polymorphisms (SNPs) in humans and quantitative trait loci in mice that influence neurodevelopment and neurodegeneration. Another major research project involves the use of transgenic mouse models of Alzheimer’s disease to investigate the role of stress in the pathogenesis of AD. The goal of our research program is to use animal models of neuropsychiatric disorders to discover therapeutic strategies to slow and prevent disease onset and progression.
Clinical Research Fellow:
Lin Lu, MD, PhD
Qian, Chen, PhD; Liping Me, PhD
Keely Murphy; Daniel Sylvester
Kate Bliznsky (PhD student rotation)
1) Genetics of Schizophrenia-Related Traits in Mice
The purpose of this ongoing Conte Center project is to identify quantitative trait loci (QTLs) that are related to the neuroanatomical abnormalities characteristic of schizophrenia, through collaborations with Washington University in St. Louis and the University of Tennessee at Memphis
2) Stress, Glucocorticoids and Alzheimer’s disease
The aim of this project is to investigate the hypothesis that stress can accelerate the rate of progression of Alzheimer’s disease via increases in glucocorticoid activity.
3) Corticotropin-releasing factor and β-amyloid: a triple transgenic mouse model
Our main goal for this project is to produce and then assess a transgenic mouse model that contains the human APP gene and conditionally overexpresses CRF in the forebrain (Tg2576 X FbCRFOE). Doing so will allow us to more directly evaluate the role of endogenous CRF release on amyloid metabolism, plaque deposition, and overall memory function.
4) Corticotropin-releasing factor receptor regulation and Alzheimer’s disease
We either acutely or chronically administer CRFR1 antagonists to Tg2576 mice to investigate the effects of this intervention on Aβ levels, amyloid plaque deposition, and memory function.
5) Corticolimbic Degeneration and Treatment of Dementia
In this project, we seek to determine whether drugs currently used to treat dementia of the Alzheimer type (DAT) alter the underlying disease process, through the assessment of neuronal structure and synaptic density in Tg2576 mice, an animal model of Alzheimer’s disease.
Dong H, Martin MV, Chambers S, Csernansky JG (2007). Spatial Relationship between synapse loss and β-amyloid deposition in Tg2576 mice. J Comparative Neurology. 500:311-321.
Kang JE, Cirrito JR, Dong H, Csernansky JG, Holtzman DM (2007). Acute stress increases interstitial fluid amyloid-beta via corticotropin-releasing factor and neuronal activity. Proc Natl Acad Sci U S A. 104(25):10673-10678.
Dong H, Martin M, Colvin J, Ali Z, Borek J, Wang L, Lu L,. Williams RW, Rosen GD, Csernansky JG, Cheverud JM (2007). Quantitative trait loci linked to thalamic and cortical gray matter volumes in BXD recombinant inbred mice. Heredity.99:62-69.
Dong H, Yuede CM, Coughlan C, Lewis B, Csernansky JG (2008). Effects of memantine on neuronal structure and conditioned fear in the Tg2576 mouse model of Alzheimer’s disease. Neuropsychopharmacology. 33:3226-3236.
Dong H, Yuede CM, Yoo HS, Martin MV, Deal C, Mace AG, Csernansky JG (2008). Corticosterone and related receptor expression are associated with increased beta-amyloid plaques in isolated Tg2576 mice. Neuroscience. 155:154-163.
303 Chicago Ave
Chicago, IL 60611