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p53 upregulated mediator of apoptosis (Puma) deficiency increases survival of adult neural stem cells generated physiologically in the hippocampus, but does not protect stem cells generated in surplus after an excitotoxic lesion

journal contribution
posted on 06.07.2021, 15:11 by Eva C Bunk, Hans-Georg König, Jochen PrehnJochen Prehn, Brian KirbyBrian Kirby

Objectives: Neurogenesis occurs in the mammalian brain throughout adulthood and increases in response to metabolic, toxic or traumatic insults. To remove potentially superfluous or unwanted neural stem cells/neuronal progenitors, their rate of proliferation and differentiation is fine-tuned against their rate of apoptosis. Apoptosis requires the transcriptional and posttranslational activation of Bcl-2-homolgy domain 3 (BH3)-only proteins. Previously, we demonstrated that the BH3-only protein p53-upregulated mediator of apoptosis (Puma) controls the physiological rate of apoptosis of neural precursor cells in the adult mouse hippocampus. Puma's role in controlling a lesion-induced increase in neural stem cells is currently not known.

Methods: We employed a model of local, N-methyl-D-asparte (NMDA)-induced excitotoxic injury to the CA1 hippocampal subfield and immunofluorescence labelling to produce increased neural stem cell proliferation/ neurogenesis in the dentate gyrus at two survival times following the excitotoxic lesion.

Results: Deletion of puma failed to rescue any NMDA-induced increase in adult born cells as assessed by BrdU or Doublecortin labelling in the long-term. No difference in the proportion of BrdU/NeuN-positive cells comparing the different genotypes and treatments suggested that the phenotypic fate of the cells was preserved regardless of the genotype and the treatment.

Conclusions: While neurogenesis is up-regulated in puma-deficient animals following NMDA-induced excitotoxicity to the hippocampal CA1 subfield, puma deficiency could not protect this surplus of newly generated cells from apoptotic cell death.

Funding

Science Foundation Ireland (08/IN1/1949; 16/RC/3948)

National Biophotonics and Imaging Platform Ireland (Higher Education Authority)

History

Comments

The final publication is available at www.degruyter.com

Published Citation

Bunk EC, König HG, Prehn JHM, Kirby BP. p53 upregulated mediator of apoptosis (Puma) deficiency increases survival of adult neural stem cells generated physiologically in the hippocampus, but does not protect stem cells generated in surplus after an excitotoxic lesion. J Basic Clin Physiol Pharmacol. 2021; 32(2):57-66

Publication Date

9 November 2020

PubMed ID

33155994

Department/Unit

  • FutureNeuro Centre
  • Physiology and Medical Physics
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Health Professions Education
  • Neurological and Psychiatric Disorders

Publisher

Walter de Gruyter GmbH

Version

  • Published Version (Version of Record)