Elsevier

Neuroscience

Volume 127, Issue 1, 2004, Pages 125-136
Neuroscience

Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain

https://doi.org/10.1016/j.neuroscience.2004.04.026Get rights and content

Abstract

Neuregulin-1 (NRG-1) plays important roles in the development and plasticity of the brain, and it has recently been identified as a susceptibility gene for schizophrenia. Though there are rodent data, little is known about its distribution in the human brain. The aim of this study was to ascertain the localization of NRG-1 and its mRNA in multiple regions of the normal adult human brain. We investigated NRG-1 mRNA in 11 subjects using in situ hybridization and northern analysis, and NRG-1 protein in six subjects using immunohistochemistry and Western blotting. NRG-1 mRNA was present as bands of approximately 2, 3 and 6 kb. It was clearly detected in the prefrontal cortex (middle laminae), hippocampal formation (except CA1), cerebellum, oculomotor nucleus, superior colliculus, red nucleus and substantia nigra pars compacta. At the cellular level, NRG1 mRNA was abundant in hippocampal and cortical pyramidal neurons and some interneurons, and in cerebellar Purkinje cells and Golgi cells. NRG-1 protein was detected as bands of approximately 140, 110, 95 and 60 kD. Immunohistochemistry revealed NRG-1 in many cell populations, consistent with the mRNA data, being prominent in pyramidal neurons, Purkinje cells, several brainstem nuclei, and white matter neurons. Moderate NRG-1 immunoreactivity was also observed in cerebellar and dentate gyrus granule cells, and some glia. Within neurons, NRG-1 staining was primarily somatodendritic; in the cell body staining was granular, with clustering close to the plasma and nuclear membranes. There was also labeling of some fiber tracts, and local areas of neuropil (e.g. in the dentate nucleus) suggestive of a pre-synaptic location of NRG-1. The data show a widespread expression of NRG-1 in the adult human brain, including, but not limited to, brain areas and cell populations implicated in schizophrenia. Using these normative data, future studies can ascertain whether the role of NRG-1 in the disease is mediated, or accompanied, via alterations in its expression.

Section snippets

Subject details

Different brain series were used for the mRNA and protein studies. Series 1 comprised 11 subjects from the Clinical Brain Disorders Branch (NIMH), mean, (S.D.); age, 47 (13) yr, range, 24–66; pH 6.5 (0.2), range, 6.14–6.87; postmortem interval (PMI) 22 (10) h, range, 10–37; and series 2, six subjects from the Oxford brain series, age 50 (22) yr, range 17–79; pH 6.49 (0.2), range, 6.27–6.89; PMI 49 (18) h, range, 20–72. Subjects had no history of neurological or psychiatric illness and

NRG-1 mRNA in the human brain

Northern blots of brain regions and lung hybridized with the NRG-1 riboprobe showed transcripts of approximately 2, 3 and 6–7 kb (data not shown), consistent with previous reports (Wen et al., 1992, Chen et al., 1994, Bermingham-McDonogh et al., 1996). For in situ hybridization, no signal was observed in any area when control sections were hybridized with sense strand riboprobe (Fig. 1A). Together these investigations indicate that riboprobe hybridization signal reflects specific detection of

Discussion

The present study shows that NRG-1 mRNA and protein continue to be expressed in many regions of the adult human brain. The northern and Western blots confirm the presences of several isoforms. NRG-1 expression is primarily but not exclusively neuronal. Within neurons, different populations have varying levels of NRG-1 mRNA and immunoreactivity, its expression being prominent in pyramidal neurons and Purkinje cells. Intra-neuronal NRG-1 shows a complex distribution, both within cell bodies,

Conclusion

Our data show a widespread and differential expression of NRG-1 in neuronal and glial populations of the adult human brain. Within neurons, NRG-1 is expressed mainly somatodendritically, but with evidence of axonal localization as well. The persistent expression of NRG-1 into adulthood supports a continuing (or different) role for NRG-1 in the functioning of the mature brain. To extend the current observations, future studies will require more comprehensive mapping, both anatomically and

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