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Volume 17, Number 19, Issue of October 1, 1997 pp. 7372-7384
Copyright ©1997 Society for Neuroscience

Deafferentation Causes Apoptosis in Cortical Sensory Neurons in the Adult Rat

Received April 18, 1997; revised June 9, 1997; accepted July 10, 1997.

Sabrina A. Capurso^{1, 4}, Michael E. Calhoun⁴, Renat R. Sukhov⁴, Peter R. Mouton^{1, 4}, Donald L. Price^{1, 2, 3, 4}, and Vassilis E. Koliatsos^{1, 2, 3, 4}

Departments of ¹ Pathology, ² Neurology, and ³ Neuroscience and ⁴ Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196

The present study provides an experimental model of the apoptotic death 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 ultrastructure were used to provide evidence of apoptosis; neurons in olfactory cortex were counted by stereology. Maximal TUNEL staining occurred in the piriform cortex between 18 and 26 hr postbulbectomy. Within the survival times used in the present study (up to 48 hr postlesion), cell death was observed exclusively in the piriform cortex; there was no evidence of cell death in any other areas connected with the olfactory bulb. Neurons undergoing apoptosis were pyramidal cells receiving inputs from, but not projecting to, the olfactory bulb. The apical dendrites of these neurons were contacted by large numbers of degenerating axonal terminals. Gel electrophoresis of DNA purified from lesioned olfactory cortex showed a ladder pattern of fragmentation. Inflammatory cells or phagocytes were absent in the environment of degenerating neurons in the early stages of the apoptotic process. The present model suggests that deafferentation injury in sensory systems can cause apoptosis. In addition, olfactory bulbectomy can be used for investigating molecular mechanisms that underlie apoptosis in mature mammalian cortical neurons and for evaluating strategies to prevent the degeneration of cortical neurons.

Key words: anterograde degeneration; cell death; DNA fragmentation; neurodegenerative disease; olfactory; TUNEL

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