The focus of my laboratory involves investigating mechanisms underlying learning and memory as well as memory loss during normal aging and age-related neurodegenerative diseases such as Alzheimer disease (AD). We are particularly interested in understanding the impact of metabolic and reproductive steroid and peptide hormone signaling on hippocampal function and plasticity; currently studied hormones include leptin, estrogen and gonadotropins. More importantly, we are interested in understanding how age-related changes in the secretion of these hormones, influences cognitive and central metabolic processes that may lead to AD development. We use animal and cellular models and a variety of techniques including behavioral testing, histology, molecular/cellular biology, and transgenic approaches to ultimately understand the basic signaling mechanisms associated with CNS hormone action with the ultimate aim to develop diagnostic and therapeutic strategies for age-related cognitive loss and AD. The other main focus of my laboratory is to begin to elucidate the molecular and biochemical mechanisms involved in the “switch” or transition from benign cognitive/neuronal aging to the development of AD using a variety of transgenic models of accelerated aging and AD. Specifically our work is focused on studying the chronology of appearance and interplay between metabolic and oxidative changes and AD pathological hallmarks and how modulating this interplay through pharmacology benefits cognition and slows down the development of AD.

1. Bryan KJ, Mudd JC, Richardson SL, Chang J, Lee HG, Zhu X, Smith MA, Casadesus G. (2010)
   Down-regulation of serum gonadotropins is as effective as estrogen replacement at improving menopause-associated cognitive deficits. J Neurochem. Feb; 4(112):870-81.
   
2. Greco SJ, Bryan KJ, Sarkar S, Zhu X, Smith MA, Ashford JW, Johnston JM, Tezapsidis N, Casadesus G. (2010)
   Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. Jan; 4(19):1155-67.
   
3. Lee HG, Casadesus G, Nunomura A, Zhu X, Castellani RJ, Richardson SL, Perry G, Felsher DW, Petersen RB, Smith MA. (2009)
   The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse. Am J Pathol. Mar; 3(174):891-7.
   
4. (2009)
   Activation of Akt by lithium: pro-survival pathways in aging. Mech Ageing Dev. Apr; 4(130):253-61.
   
5. Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X. (2008)
   Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci U S A. Dec 9; 49(105):19318-23.