Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 39, Pages 14264-14269Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0404364101
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Funding
- NIA NIH HHS [R01 AG016263, R01 AG16263] Funding Source: Medline
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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.
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