Apoptosis

, Volume 12, Issue 5, pp 993–1010 | Cite as

Pathological apoptosis in the developing brain

Article

Abstract

More than half of the initially-formed neurons are deleted in certain brain regions during normal development. This process, whereby cells are discretely removed without interfering with the further development of remaining cells, is called programmed cell death (PCD). The term apoptosis is used to describe certain morphological manifestations of PCD. Many of the effectors of this developmental cell death program are highly expressed in the developing brain, making it more susceptible to accidental activation of the death machinery, e.g. following hypoxia-ischemia or irradiation. Recent evidence suggests, however, that activation and regulation of cell death mechanisms under pathological conditions do not exactly mirror physiological, developmentally regulated PCD. It may be argued that the conditions after e.g. ischemia are not even compatible with the execution of PCD as we know it. Under pathological conditions cells are exposed to various stressors, including energy failure, oxidative stress and unbalanced ion fluxes. This results in parallel triggering and potential overshooting of several different cell death pathways, which then interact with one another and result in complex patterns of biochemical manifestations and cellular morphological features. These types of cell death are here called “pathological apoptosis,” where classical hallmarks of PCD, like pyknosis, nuclear condensation and caspase-3 activation, are combined with non-PCD features of cell death. Here we review our current knowledge of the mechanisms involved, with special focus on the potential for therapeutic intervention tailored to the needs of the developing brain.

Keywords

Brain development Hypoxia-ischemia Irradiation 

Abbreviations

AIF

apoptosis-inducing factor

AMPA

alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid

APAF-1

apoptosis protease-activating factor-1

BDNF

brain-derived neurotrophic factor

CREB

cAMP-response element-binding protein

DG

dentate gyrus

EE

early elimination

ERK

extracellular signal-regulated protein kinase

HI

hypoxia-ischemia

IL

interleukin

JNK

jun N-terminal kinase

MAP kinase

mitogen-associated protein kinase

mtPT

mitochondrial permeability transition

NOS

nitrogen oxide synthase

NGF

nerve growth factor

NMDAR

N-methyl-D-aspartate receptor

P7

postnatal day 7

PCD

programmed cell death

ROS

reactive oxygen species

SGZ

subgranular zone (of the dentate gyrus)

SOD2

superoxide dismutase 2

SVZ

subventricular zone (of the lateral ventricular wall)

TRX 2

thioredoxin 2

XIAP

X-linked inhibitor of apoptosis protein

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Copyright information

© Springer Science + Business Media, LLC 2007

Authors and Affiliations

  1. 1.Center for Brain Repair and RehabilitationInstitute of Neuroscience and Physiology, Göteborg UniversityGöteborgSweden
  2. 2.University of KonstanzKonstanzGermany
  3. 3.CNRS-UMR 5091, Physiologie Cellulaire de la SynapseUniversité Bordeaux 2Bordeaux CédexFrance

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