Editing Programmed cell death (section)

===Peripheral versus central nervous system===
[[File:Programmed cell death in the peripheral and central nervous system.jpg|thumb|right|Cell death in the peripheral vs central nervous system]]

Different mechanisms regulate PCD in the [[peripheral nervous system]] (PNS) versus the [[central nervous system]] (CNS). In the PNS, innervation of the target is proportional to the amount of the target-released neurotrophic factors NGF and [[NT3]].<ref name="Weltman">{{cite journal|last=Weltman|first=JK|title=The 1986 Nobel Prize for Physiology or Medicine awarded for discovery of growth factors: Rita Levi-Montalcini, M.D., and Stanley Cohen, Ph.D.|journal=New England Regional Allergy Proceedings|date=February 8, 1987|pmid=3302667|doi=10.2500/108854187779045385|volume=8|issue=1|pages=47–8}}</ref><ref name="Dekkers1">{{cite journal|last=Dekkers|first=M|title=Programmed Cell Death in Neuronal Development|journal=Science|date=April 5, 2013|volume=340|issue=6128|pages=39–41|doi=10.1126/science.1236152|pmid=23559240|bibcode=2013Sci...340...39D|s2cid=206548254}}</ref> Expression of neurotrophin receptors, [[TrkA]] and [[TrkC]], is sufficient to induce [[apoptosis]] in the absence of their [[ligands]].<ref name="Dekkers" /> Therefore, it is speculated that PCD in the PNS is dependent on the release of neurotrophic factors and thus follows the concept of the neurotrophic theory.{{cn|date=November 2024}}

Programmed cell death in the CNS is not dependent on external [[growth factors]] but instead relies on intrinsically derived cues. In the [[neocortex]], a 4:1 ratio of excitatory to inhibitory [[interneurons]] is maintained by apoptotic machinery that appears to be independent of the environment.<ref name="Dekkers1" /> Supporting evidence came from an experiment where interneuron progenitors were either transplanted into the mouse neocortex or cultured [[in vitro]].<ref name="Southwell">{{cite journal|last=Southwell|first=D.G.|title=Intrinsically determined cell death of developing cortical interneurons|journal=Nature|date=November 2012|volume=491|issue=7422|pages=109–115|doi=10.1038/nature11523|pmid=23041929|pmc=3726009|bibcode=2012Natur.491..109S}}</ref> Transplanted cells died at the age of two weeks, the same age at which endogenous interneurons undergo apoptosis. Regardless of the size of the transplant, the fraction of cells undergoing apoptosis remained constant. Furthermore, disruption of [[TrkB]], a receptor for [[brain derived neurotrophic factor]] (Bdnf), did not affect cell death. It has also been shown that in mice null for the proapoptotic factor [[Bcl-2-associated X protein|Bax]] (Bcl-2-associated X protein) a larger percentage of interneurons survived compared to wild type mice.<ref name="Southwell" /> Together these findings indicate that programmed cell death in the CNS partly exploits Bax-mediated signaling and is independent of BDNF and the environment. Apoptotic mechanisms in the CNS are still not well understood, yet it is thought that apoptosis of interneurons is a self-autonomous process.{{cn|date=November 2024}}