DEAFFERENTATION CAUSES APOPTOSIS IN CORTICAL SENSORY NEURONS IN THE ADULT-RAT

The present study provides an experimental model of the apoptotic deat h of pyramidal neurons in rat olfactory cortex after total bulbectomy, Terminal transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP) -biotin nick end labeling (TUNEL), DNA electrophoresis, and neuronal u ltrastructure were used to provide evidence of apoptosis; neurons in o lfactory cortex were counted by stereology, Maximal TUNEL staining occ urred in the piriform cortex between 18 and 26 hr postbulbectomy, With in the survival times used in the present study (up to 48 hr postlesio n), cell death was observed exclusively in the piriform cortex; there was no evidence of cell death in any other areas connected with the ol factory bulb. Neurons undergoing apoptosis were pyramidal cells receiv ing inputs from, but not projecting to, the olfactory bulb. The apical dendrites of these neurons were contacted by large numbers of degener ating axonal terminals, Gel electrophoresis of DNA purified from lesio ned olfactory cortex showed a ladder pattern of fragmentation. Inflamm atory cells or phagocytes were absent in the environment of degenerati ng neurons in the early stages of the apoptotic process, The present m odel suggests that deafferentation injury in sensory systems can cause apoptosis, In addition, olfactory bulbectomy can be used for investig ating molecular mechanisms that underlie apoptosis in mature mammalian cortical neurons and for evaluating strategies to prevent the degener ation of cortical neurons.