Neuronal nuclear antigen (NeuN): a useful marker of neuronal immaturity in sudden unexplained perinatal death

J Neurol Sci. 2013 Jun 15;329(1-2):45-50. doi: 10.1016/j.jns.2013.03.012. Epub 2013 Apr 7.


Introduction: In the developing brain neuronal differentiation is associated with permanent exit from the mitotic cycle. Neuronal nuclear antigen (NeuN) is a nuclear protein widely expressed in the mature postmitotic neurons.

Methods: We applied NeuN immunocytochemistry in 65 cases of perinatal death (16 victims of sudden intrauterine unexplained death syndrome/SIUDS, 19 of sudden infant death syndrome/SIDS and 30 controls) to test the physiological status of the brain neurons. In addition we applied both TUNEL and Caspase 3 immunohistochemical methods in order to highlight a possible relation between decreased NeuN expression and apoptotic outcome. We also attempted to see whether or not NeuN pathological changes can be related to cigarette smoke absorption in pregnancy.

Results: NeuN staining was considerably reduced or lost in SIUDS/SIDS compared to controls. However neurons with decreased NeuN-labeling showed no sign of apoptosis. A significant association was found between NeuN depletion and maternal smoking.

Conclusion: Altered NeuN expression can be a marker of immature and/or suffering neurons. The exclusive presence of this pattern of expression in SIUDS/SIDS victims, leads us to recommend the NeuN immunohistochemistry as a routine method in neuropathological protocols to convalidate a diagnosis of sudden perinatal death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Antigens, Nuclear / metabolism*
  • Brugada Syndrome / pathology*
  • Caspase 3 / metabolism
  • Female
  • Fetus
  • Gestational Age
  • Humans
  • In Situ Nick-End Labeling
  • Infant, Newborn
  • Male
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Pregnancy


  • Antigens, Nuclear
  • Nerve Tissue Proteins
  • neuronal nuclear antigen NeuN, human
  • Caspase 3

Supplementary concepts

  • Sudden unexpected nocturnal death syndrome