Lavezzi AM, Corna MF, Matturri L. Neuronal nuclear antigen (NeuN): a useful marker of neuronal immaturity in sudden unexplained perinatal death. J Neurol Sci 329: 45-50

"Lino Rossi" Research Center for the study and prevention of unexpected perinatal death and SIDS Department of Surgical, Reconstructive and Diagnostic Sciences, University of Milan, Italy. Electronic address: .
Journal of the neurological sciences (Impact Factor: 2.47). 04/2013; 329(1-2). DOI: 10.1016/j.jns.2013.03.012
Source: PubMed


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.

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.

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.

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.

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    • "As the neuronal nuclear antigen (NeuN) is a nuclear protein widely expressed in the mature postmitotic neurons, it has been commonly used as a neuron-specific marker for mature neurons [22]. We thus stained the cells with a NeuN specific antibody and found that at least 10% cells were positive in NeuN expression in each of the three converted cell types after nineteen days of the reprogramming (Fig. 2A). "
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    ABSTRACT: Recent advances in trans-differentiation of one type cell to another have made it possible to directly convert Huntington's disease (HD) patient fibroblasts into neurons by modulation of cell-lineage-specific transcription factors or RNA processing. However, this possibility has not been examined. Here, we demonstrate that HD patient-derived fibroblasts can be directly trans-differentiated into neuron-like cells by knockdown of the expression of a single gene encoding the polypyrimidine-tract-binding protein. The directly converted HD neuron-like cells were positive in expression of Tuj1, NeuN, DARPP-32, and γ-aminobutyric acid and exhibited neuritic breakdown, abnormal neuritic branching, increased cell death, and aggregation of mutant huntingtin. These observations indicate that the neuron-like cells directly converted from HD patient fibroblasts recapitulate the major aspects of neuropathological characteristics of HD and thus provide an additional model for understanding the disorder and validation of therapeutic reagents.
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    ABSTRACT: We investigated the immunohistochemical expression of substance P (SP) in the brainstems of 56 subjects aged from 17 gestational weeks to 10 post natal months, who died of unknown (sudden unexplained fetal deaths and SIDS) and known causes (controls). The goals of this study were: (i) to obtain basic information about the expression of SP during the first phases of human nervous system development; (ii) to evaluate whether there are alterations of this neuromodulator in victims of sudden death; and (iii) to verify any correlation with maternal cigarette smoking. Immunohistochemistry demonstrated SP immunoreactivity in the caudal trigeminal nucleus area, with a progressive increase in the density of SP-positive fibers of the corresponding tract during normal development from fetal life to the first post natal months. Delineation of the structure of the human trigeminal nucleus, little investigated so far, provided essential data on its morphologic and functional development. Instead, a negative or low SP expression was detectable in the fibers of this tract in a wide subset of SIDS victims and, conversely, a high SP-expression in a wide subset of sudden fetal deaths. We postulate, on the basis of these results, that SP has a functional importance in the early phases of central nervous system development and in the regulation of autonomic functions. In addition, the observation of a significant correlation between sudden unexplained death, altered SP staining and maternal smoking leads us to suggest a close relation between the absorption of cigarette smoke in utero and a decreased functional activity of the trigeminal nucleus, that can trigger sudden death of the fetus during pregnancy or of the infant in the first months of life.
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    ABSTRACT: The present study was aimed at supplementing our previous investigations on the morphological features of the Purkinje cells during the autonomic nervous system development, particularly in victims of sudden perinatal death (Sudden Intrauterine Unexplained Death Syndrome and Sudden Infant Death Syndrome), given their crucial role in determining connectivity patterns in the brain as well as in the control of autonomic functions. We highlighted in these pathologies, and precisely in 21 cases of sudden foetal death and 26 cases of sudden infant death, a high percentage of developmental defects of the Purkinje cells such as heterotopia, hypoplasia, hyperplasia, mitotic and/or shrunken features and abnormal neuronal nuclear antigen expression. These alterations can be interpreted as a result of a defective maturation and/or migration of Purkinje cells in foetal cerebellum, likely consequence of exposure to injuries, particularly to maternal cigarette smoke. Interestingly, we observed in sudden perinatal deaths an association with similar developmental defects of both the dentate and the inferior olivary nuclei. This suggests the existence of a Purkinje-Olivo-Dentate network playing a fundamental role in triggering a sudden death mechanism in perinatal life in the presence of specific risk factors.
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