Cortical interneurons become activated by deafferentation and instruct the apoptosis of pyramidal neurons.
Unlike peripheral nervous system neurons and certain groups of nerve cells in the CNS, cortical projection neurons are tolerant of axonal lesions. This resistance is incongruent with the massive death of pyramidal neurons in age-associated neurodegenerative diseases that proceed along corticocortical connections. Some insights have emerged from our previous work showing that pyramidal cells in piriform cortex undergo classical apoptosis within 24 h after bulbectomy via transsynaptic, but not retrograde, signaling. These findings allow the investigation of cellular and molecular changes that take place in the context of experimental cortical degeneration. In the present study, we show that the transsynaptic death of pyramidal neurons in piriform cortex is a nitric oxide-mediated event signaled by activated interneurons in layer I. Thus, we demonstrate that cortical interneurons play an essential role in transducing injury to apoptotic signaling that selectively targets pyramidal neurons. We propose that this mechanism may be generic to cortical degenerations and amenable to therapeutic interventions.
Koliatsos
V E
VE
Department of Pathology, Division of Neuropathology, Institute for Cell Engineering, The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA. koliat@jhmi.edu
Dawson
T M
TM
Kecojevic
A
A
Zhou
Yueping
Y
Wang
Yi-Feei
YF
Huang
K-X
KX
D000344:Afferent Pathways / Q000473:pathology / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D003714:Denervation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009252:NADPH Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009833:Olfactory Pathways / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction; D013569:Synapses / Q000473:pathology / Q000502:physiology; D015854:Up-Regulation
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D012697:Serine Endopeptidases