Olig2 and Glial Fate in the SVZ

The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA nicks and thus promotes DNA repair. The addition of ADP-riboses to acidic amino acid residues modifies the chromatin structure and affects DNA transcription and repair. This week, Visochek et al. provide data indicating that neurotrophins can also trigger PARP-1 activation. Brief exposures of cultured cortical neurons to nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-3 (NT-3) or to two “neuroprotective peptides” [NAP and activity-dependent neurotrophic factor-9 (ADNF-9)] induced increases in PARP-1 activity as measured by ADP-ribose polymer immunoreactivity or PARP-1 auto-polyADP-ribosylation. Pharmacological studies indicated that the signaling cascade involved tropomyosin-related kinase receptor phosphorylation, calcium release from intracellular stores, and calciumdependent kinases. However, neurotrophin treatment did not produce detectable DNA damage. PARP-1 was also implicated in the NGF-mediated neurite outgrowth in pheochromocytoma 12 cells. The histone H1 was polyADPribosylated after neurotrophin treatment, potentially rendering DNA accessible to transcription factors and repair enzymes.