Bookmark and Share

Paul J Yarowsky
 

Paul J Yarowsky Ph.D.

Academic Title: Associate Professor
Primary Appointment: Pharmacology
pyarowsk@umaryland.edu
Location: BRB 4-002
Phone: (410) 706-3134

Research Interests:

Neuroscience and Membrane Biology
The principal research interests of this laboratory are concerned with understanding how cognitive and neurodegeneration disorders such as Down syndrome (DS) and Alzheimer’s disease may result from abnormal brain development and increased apoptosis. We are specifically concerned with understanding mechanisms of brain development and aging deficits in the trisomy 16 (Ts16) mouse, a such as neuronal proliferation, differentiation, and death. Our most recent work has focused on neurological potential animal model for impaired neuron survival, defective Ca2+ Alzheimer’s disease and Down syndrome. We have found that there is abnormal neuronal proliferation, homeostasis in astrocytes and neurons, and spatial learning and memory deficits.

Abnormal Cortical Development
We have determined that cerebral cortical development in Ts16 occurs abnormally. Tangential expansion of the cortex is slowed in Ts16 resulting in a reduction of final telencephalic size. In addition, there is a delay in the growth of the postmitotic layers of the cortex during mid-gestation, but the radial growth of the cortex attains normal thickness during the later part of the embryonic period. These defects constitute a distinctive phenotype in Ts16 which is similar to what is known about DS cortical development. We have determined that abnormalities in neuroblast proliferation and apoptosis contribute to this phenotype. Cell cycle duration is increased in Ts16 neuroblasts due to a longer DNA synthetic phase, and fewer cells in the Ts16 ventricular germinal zone become postmitotic and leave the germinal zone than in diploid litermates. During this period of excessive neuron generation in Ts16, we have observed a large increase in apoptosis in both the germinal zone and in postmitotic layers, suggesting that the increased death acts to compensate for the overproduction of neurons. In addition, since the timing of this delay in radial growth coincides with initial formation of cortical connections, we are investigating whether the delay leads to abnormal connectivity in the Ts16 that parallels abnormalities occurring in DS; studies are underway to test whether in DS similar developmental cortex. These developmental disorders in the Ts16 mouse cortex predict later cognitive dysfunction. In the partial Ts16 mouse (that survives to adulthood), we have found deficits in spatial learnimg and memory (below). Studies are currently underway to investigate whether similar abnormalities during cortical development occur in DS.


Training History:

I received my Ph.D. from the Department of Physiology at The George Washington University in 1976 and subsequently conducted research as a postdoctoral fellow with Donald McAffee (City of Hope Medical Center) and Louis Sokoloff (NIMH). I came to the University of Maryland School of Medicine in 1981. Support for my laboratory comes from the NSF and the NIH. I teach in the Developmental Neurobiology course and in the Pathophysiology and Therapeutics course.

Publications:

Goldman, W.F., Yarowsky, P.J., Juhaszova, M., Krueger, B.K., and Blaustein, M.P. Sodium/calcium exchange in rat cortical astrocytes. J. Neurosci. 14:5834-5843 (1994).

Yarowsky, P.J., Brougher, D.S., and Krueger, B.K. Glucocorticoid stimulation of sodium channel expression in cultured astrocytes. Ann. N.Y. Acad. Sci. 746: 480-485 (1994).

Schaller, K.L., Krzemien, D.M., Yarowsky, P.J., Krueger, B.K., Mandel, G., and Caldwell, J.H. NaCh6: A novel, abundant sodium channel expressed in neurons & glia. J Neurosci. 15:3231-3242 (1995).

Bambrick, L.L., Yarowsky, P.J., and Krueger, B.K. Glutamate as a hippocampal neuron survival factor: An inherited defect in the trisomy 16 mouse. Proc. Natl Acad. Sci. USA 92: 9692-9696 (1995).

Golovina, V.A., Bambrick, L.L., Yarowsky, P.J., Krueger, B.K., and Blaustein, M.P. Modulation of two functionally distinct endoplasmic reticulum Ca2+stores in astrocytes: Role of the plasmalemmal Na/Ca exchange. Glia 16: 296-305 (1996).

Bambrick, L.L., Yarowsky, P.J., and Krueger, B.K. Glutamate-promoted survival in hippocampal neurons: A defect in the mouse trisomy 16. In: Fiskum, G., ed. Neurodegenerative Diseases. New York: Plenum Press, 1996:133-139.

Klein, S.L., Kriegsfeld, L.J., Hairston, J.E., Rao, V., Nelson, R.J., and Yarowsky, P.J. Characterization of sensorimotor performance, reproductive, and aggressive behaviors in segmental trisomic 16(Ts65Dn) mice. Physiology and Behavior 60: 1159-1164 (1996).

Demas, G.E., Nelson, R.J., Krueger, B.K., and Yarowsky, P.J. Spatial memory deficits in segmental trisomic Ts65Dn mice. Behav. Brain Res. 82: 85-92 (1996).

Bambrick, L.L., de Grip, A., Seenivasan, V., Krueger, B.K. and Yarowsky, P.J. Expression of glial antigens in mouse astrocytes: Species differences and regulation in vitro. J Neurosci Res. 46: 305-315 (1996).

Haydar, T.H., Blue, M.E., Molliver, M.E., Krueger, B.K., and Yarowsky, P.J. Consequences of trisomy 16 for mouse brain development: Corticogenesis in a model of Down syndrome. J.Neurosci. 16:6175-6182 (1996).

Bambrick, L.L., Golovina, V.A., Yarowsky, P.J., Krueger, B.K., and Blaustein, M.P. Abnormal calcium homeostasis in astrocytes from the trisomy 16 mouse. Glia 19: 352-358 (1997).

Demas, G.E., Nelson, R.J., Krueger, B.K., and Yarowsky, P.J. Impaired spatial working and reference memory in segmental trisomic Ts65Dn mice Behav. Brain Res. (in press).