Cellular neuroscienceHistochemical evidence for wide expression of the metalloendopeptidase nardilysin in human brain neurons
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Adult brains
All brains were obtained from pathologists or from medical examination officers, with the full consent of each family and in accordance with the ethics and rules outlined by German law and the local ethics commission of the University of Magdeburg. Brains of six individuals without neurological or psychiatric disorders (three males, 49, 54 and 63 years; three females, 54, 55 and 61 years) were studied.
Brains were removed between 9 and 48 h after death. Tissue preparation was performed as
Western blot analysis of NRDc in human brain samples
Using Western blotting (Fig. 1A) we could detect NRDc in the lysates from human cerebellar cortex (lane 2), temporal (lane 3) and prefrontal cortex (lane 4) by using two different antisera, i) the goat anti-NRDc antiserum which was also used for the immunohistochemical studies below and ii) a rabbit anti-NRDc antiserum which we used in our previous studies on the interaction of NRDc with the brain-specific protein p42IP4 (Stricker et al., 2006). Both antisera detect NRDc as a band with an
Discussion
This is the first report describing the regional distribution and cellular localization of NRDc in human brain. Since the precise functional importance of NRDc for the CNS is largely unknown, detailed knowledge of its anatomical localization within the brain might help to learn more about its functional role. Our immunohistochemical and Western blot findings show that the protein is widely distributed in the adult human brain. Table 1 summarizes the regional distribution and cellular
Conclusions
The metalloendopeptidase NRDc is widely but unevenly distributed in the human brain. Its cellular localization is confined to neurons. The nearly ubiquitous distribution in the perinatal neocortex points to an important role in brain development. The protease was found to be partially co-expressed with parvalbumin and p42IP4 but not with calretinin, GFAP or somatostatin-28. Our failure to identify neurons which co-express NRDc and somatostatin-28 does not necessarily question the proposed role
Acknowledgments
This work was partially supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 426, TP A4 (G.R.), the Stanley Foundation (H.-G.B.), and Bundesministerium für Bildung und Forschung, grant NBL-3, 01ZZ0407.
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Decreased expression of nardilysin in SH-SY5Y cells under ethanol stress and reduced density of nardilysin-expressing neurons in brains of alcoholics
2013, Journal of Psychiatric ResearchCitation Excerpt :High levels of NRDc are found in the fetal brain suggesting a role of the enzyme in neuronal development (Fumagalli et al., 1998; Bernstein et al., 2007). In the adult brain, NRDc is widely expressed in neurons of different areas (Bernstein et al., 2007). Functionally, NRDc is thought to contribute to the turnover of various neuropeptides in the CNS.
Nardilysin
2013, Handbook of Proteolytic EnzymesRetinoic acid-induced upregulation of the metalloendopeptidase nardilysin is accelerated by co-expression of the brain-specific protein p42<sup>IP4</sup> (centaurin α1; ADAP1) in neuroblastoma cells
2011, Neurochemistry InternationalCitation Excerpt :Like other neuroblastoma cell lines, SH-SY5Y cells can be differentiated into a neuronal-like cell type, when exposed to low concentrations of RA (Pahlman et al., 1984). We could recently demonstrate that in the human brain NRD is expressed almost exclusively in neurons with a clear overlap of the expression of p42IP4 and NRD (Bernstein et al., 2007). To elucidate the functional interaction of both proteins, we here investigated firstly, whether p42IP4 is a substrate for NRD, or whether it can influence the kinetics of the activity of NRD in vitro.
A meta-analysis of two genome-wide association studies identifies 3 new loci for alcohol dependence
2011, Journal of Psychiatric ResearchCitation Excerpt :Previously, it has been suggested that NRD1 gene at 1p32.3 might play specific roles in neuronal development using mouse model (Fumagalli et al., 1998). Recently, Bernstein et al. (2007) demonstrated that NRD1 enzyme was widely, but unevenly, expressed in the human brain and NRD1 might possibly play a role in brain development. More recently, it has been shown that NRD1/NRDc is a critical regulator axonal maturation and myelination, which are essential processes for establishing an efficient neuronal signaling network (Ohno et al., 2009).