O'Kusky, John
Associate Professor, Dept of Pathology and Laboratory Medicine
B.Sc. (Loyola, Chicago)
M.Sc. (Ottawa)
Ph.D. (Laval)
Research Interests
The research program in this laboratory is concerned with the developmental neurobiology of the mammalian brain and with the pathogenesis of developmental disorders of the central nervous system.
The normal development of the central nervous system is characterized by a series of progressive events which include neuron proliferation, migration, neuronal differentiation, growth of dendritic and axonal processes, synaptogenesis and myelination. A number of regressive events occur during normal prenatal and early postnatal development, resulting in the death of specific neurons (programmed cell death) or in the elimination of axons and synapses from viable neurons (axon remodelling and synapse elimination). Ongoing research in this laboratory is designed (1) to investigate the factors controlling both the progressive and regressive phases of neurogenesis and synaptogenesis during normal development, and (2) to document the extent to which abnormalities in these progressive and regressive events contribute to various developmental disorders. At present, the roles of the insulin-like growth factor-I (IGF-I) in promoting neuron proliferation and in inhibiting neuronal apoptosis are being investigated in transgenic mice with altered expression of IGF-I
Research laboratories are equipped for most techniques in light and electron microscopy, including histochemistry, immunohistochemistry, in situ hybridization of nucleic acid probes, and axonal tract tracing. Microscopes are equipped for computer-assisted image analysis, including stereology, microdensitometry and 3-dimensional image reconstruction. Facilities for cell culture, neurochemistry and molecular biology are available.
Selected Publications
Popken, G, R.D. Hodge, P. Ye, A. J. Zhang, W. Ng, J.R. O'Kusky and A.J. D'Ercole (2004) In vivo effects of insulin-like growth factor-I (IGF-I) on prenatal and early postnatal development of the central nervous system. European J Neurosci 19:1-13
O'Kusky, J.R., P. Ye and A.J. D'Ercole (2003) Increased expression of insulin-like growth factor-I augments the progressive phase of synaptogenesis without preventing synapse elimination in the hypoglossal nucleus. J Comp Neurol 464:382-391
D'Ercole, A.J., P. Ye and J.R. O'Kusky (2002) Mutant mouse models of insulin-like growth factor actions in the central nervous system. Neuropeptides 36:209-220
O'Kusky JR, Ye P and D'Ercole AJ. 2000. Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development. J Neurosci 20(22):8435-8442
Dentrement KD, Ye P, D'Ercole AJ and O'Kusky JR. 1999. Increased insulin-like growth factor-I (IGF-I) expression during early postnatal development differentially increases neuron number and growth in medullary nuclei of the mouse. Dev Brain Res 114:135-141
O'Kusky JR, Nasir J, Cicchetti F, Parent A and Hayden MR. 1999. Neuronal degeneration in the basal ganglia and loss of pallido-subthalamic synapses in mice with targeted disruption of the
O'Kusky JR. 1998. Postnatal changes in the numerical density and total number of asymmetric and symmetric synapses in the hypoglossal nucleus of the rat. Dev Brain Res 108:179-191
O'Kusky JR, Akers MA and Vinters HV. 1996. Synaptogenesis in hemimegalencephaly: The numerical density of asymmetric and symmetric synapses in the cerebral cortex. Acta Neuropathol 92:156-163