Deafferentation Causes Apoptosis in Cortical Sensory Neurons in the Adult Rat

Abstract

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.

NMDA inhibitors cause apoptosis of pyramidal neurons in mature piriform cortex: Evidence for a nitric oxide-mediated effect involving inhibitory interneurons

“…The second cell, i.e. the relay neuron whose cell body is located in layer IIα, is the target of nitric oxide and the primary site of apoptotic signaling, presumably after initial vacuolization injury to its dendrites that lie in direct proximity to the cell bodies and axon branches of layer I interneurons (Capurso et al, 1997) (Fig. 7).…”

“…7). Direct injury to the cell body cannot be ruled out, especially as the latter is located within the 100 μm radius of NO diffusion from the axon branches of layer I interneurons to layer IIα (Capurso et al, 1997). NO can permeate the plasma membrane and destroy post-synaptic structures via the generation of reactive oxygen species (especially peroxynitrite) within the dendrites and cell body (Bonfoco et al, 1995;Koliatsos et al, 2004).…”

“…We have previously demonstrated the vulnerability of a population of layer II neurons in piriform cortex to lesions that disconnect this cortical area from modality-specific afferents originating in the olfactory bulb (Capurso et al, 1997). These neurons are modified pyramidal cells that are located superficially in layer II and are often described as semilunar neurons based on their shape after Golgi impregnation.…”

Olfactory system modulation of hippocampal cell death

“…TUNEL labeling was visualized with diaminobenzidine chromogen, and slides coverslipped and coded for subsequent blind cell counts. For this study, labeled cell types were not identified as to glial or neuronal origin, though previous studies have demonstrated the majority of piriform cortical cells undergoing apoptosis after bulbectomy are semilunar pyramidal neurons [5].…”

“…Semilunar pyramidal cells in Layer IIa of the piriform cortex undergo rapid apoptosis following either loss of afferent input due to bulbectomy [17,19] or decreased afferent activity due to sensory deprivation [17]. Death of semilunar cells in the bulbectomy model is not mediated by axotomy, since they do not send axons back to the olfactory bulb [5,8,10,13], but rather appears to be mediated by a sudden surge of glutamate release from isolated mitral cell axon terminals within piriform cortex and a resulting glutamate-mediated nitric oxide initiated apoptotic cascade [14,30].…”