Morte celular programada: Diferenzas entre revisións

A morte celular programada pode ser reducida ou eliminada no sistema nervioso en desenvolvemento pola [[deleción]] específica de xenes proapoptóticos ou pola sobreexpresión de xenes antiapoptóticos. A ausencia ou redución de MCP pode causar serias malformacións anatómicas, pero tamén pode ter mínimas consecuencias dependendo do xene afectado, a poboación neuronal, e o estadio do desenvolvemento.<ref name="Buss" /> A proliferación excesiva de células proxenitoras que orixina importantes anormalidades cerebrais adoita a ser letal, como se observa nos [[rato knockout|ratos knockout]] para a [[caspase-3]] ou [[caspase-9]], que causa o esenvolvemento de [[exencefalia]] no [[prosencéfalo]].<ref name=Kuida>{{cite journal|last=Kuida|first=K|title=Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9|journal=Cell|year=1998|volume=94|pages=325–337|doi=10.1016/s0092-8674(00)81476-2|pmid=9708735}}</ref><ref name="Kuida decreased">{{cite journal|last=Kuida|first=K|title=Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice|journal=Nature|year=1996|volume=384|pages=368–372|doi=10.1038/384368a0|issue=6607}}</ref> porén, o [[tronco encefálico]], a [[medula espiñal]], e os [[ganglio nervioso|ganglios periféricos]] destes ratos desenvólvense normalmente, o que indica que a implicación das [[caspase]]s na MCP durante o desenvolvemento depende da rexión do cerebro e do tipo celular.<ref name="Oppenheim caspase">{{cite journal|last=Oppenheim|first=RW|title=Programmed cell death of developing mammalian neurons after genetic deletion of caspases|journal=Journal of Neuroscience|year=2001|volume=21|pages=4752–4760|accessdate=26 February 2014}}</ref> O [[knockout de xenes|knockout]] ou a inhibición do factor 1 activador da protease apoptótica ([[APAF1]]), tamén ten como resultado malformacións e un incremento da letalidade embrionaria.<ref name=Cecconi>{{cite journal|last=Cecconi|first=F|title=Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development|journal=Cell|year=1998|volume=94|pages=727–737|doi=10.1016/s0092-8674(00)81732-8}}</ref><ref name=Hao>{{cite journal|last=Hao|first=Z|title=Specific ablation of the apoptotic functions of cytochrome c reveals a differential requirement for cytochrome c and Apaf-1 in apoptosis|journal=Cell|year=2005|volume=121|pages=579–591|doi=10.1016/j.cell.2005.03.016}}</ref><ref name=Yoshida>{{cite journal|last=Yoshida|first=H|title=Apaf1 is required for mitochondrial pathways of apoptosis and brain development|journal=Cell|year=1998|volume=94|pages=739–750|doi=10.1016/s0092-8674(00)81733-x}}</ref> A manipulación das proteínas reguadoras da apoptose [[Bcl-2]] e Bax (sobreexpresión de Bcl-2 ou deleción de Bax) produce un incremento no número de neuronas en certas rexións do sistema nervioso, como a [[retina]], [[núcleo do trixémino]], [[cerebelo]] e medula espiñal.<ref name=Bonfanti>{{cite journal|last=Bonfanti|first=L|title=Protection of retinal ganglion cells from natural and axotomy-induced cell death in neonatal transgenic mice overexpressing bcl-2|journal=Journal of Neuroscience|year=1996|volume=16|pages=4186–4194|accessdate=27 February 2014}}</ref><ref name=Martinou>{{cite journal|last=Martinou|first=JC|title=Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia|journal=Neuron|year=1994|volume=13|pages=1017–1030|doi=10.1016/0896-6273(94)90266-6}}</ref><ref name=Zanjani>{{cite journal|last=Zanjani|first=HS|title=Increased cerebellar Purkinje cell numbers in mice overexpressing a human bcl-2 transgene|journal=Journal of Computational Neurology|year=1996|volume=374|pages=332–341|doi=10.1002/(sici)1096-9861(19961021)374:3<332::aid-cne2>3.0.co;2-2}}</ref><ref name=Zup>{{cite journal|last=Zup|first=SL|title=Overexpression of bcl-2 reduces sex differences in neuron number in the brain and spinal cord|journal=Journal of Neuroscience|year=2003|volume=23|pages=2357–2362|accessdate=27 February 2014}}</ref><ref name=Fan>{{cite journal|last=Fan|first=H|title=Elimination of Bax expression in mice increases cerebellar Purkinje cell numbers but not the number of granule cells|journal=Journal of Computational Neurology|year=2001|volume=436|pages=82–91|doi=10.1002/cne.1055.abs}}</ref><ref name=Mosinger>{{cite journal|last=Mosinger|first=Ogilvie|title=Suppression of developmental retinal cell death but not of photoreceptor degeneration in Bax-deficient mice|journal=Investigative Ophthalmology & Visual Science|year=1998|volume=39|pages=1713–1720|accessdate=26 February 2014}}</ref><ref name=White>{{cite journal|last=White|first=FA|title=Widespread elimination of naturally occurring neuronal death in Bax-deficient mice|journal=Journal of Neuroscience|year=1998|volume=18|pages=1428–1439|accessdate=27 February 2014}}</ref> Non obstante, a MCP de neuronas debido á deleción de Bax ou a sobreexpresión de Bcl-2 non orixina anoemalidades mmorfolóxicas prominentes nin de comportamento nos ratos. Por exemplo, os ratos que sobreexpresan Bcl-2 teñen xeralmente habilidades motoras e visión normais e ó mostran alteración en comportamentos complexos como a aprendizaxe e a ansiedade.<ref name=Gianfranceschi>{{cite journal|last=Gianfranceschi|first=L|title=Behavioral visual acuity of wild type and bcl2 transgenic mouse|journal=Vision Research Journal|year=1999|volume=39|pages=569–574|doi=10.1016/s0042-6989(98)00169-2}}</ref><ref name=Rondi>{{cite journal|last=Rondi-Reig|first=L|title=To die or not to die, does it change the function? Behavior of transgenic mice reveals a role for developmental cell death|journal=Brain Research Bulletin|year=2002|volume=57|pages=85–91|doi=10.1016/s0361-9230(01)00639-6}}</ref><ref name="Rondi Transgenic Mice">{{cite journal|last=Rondi-Reig|first=L|title=Transgenic mice with neuronal overexpression of bcl-2 gene present navigation disabilities in a water task|journal=Neuroscience|year=2001|volume=104|pages=207–215|doi=10.1016/s0306-4522(01)00050-1}}</ref> Os [`[fenotipo]]s de comportamneto normais destes ratos indican que pode estar implicado un mecanismo adaptativo para compensar o exceso de neuronas.<ref name="Buss" />