Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

Abstract

Abstract. Cytoglobin (Cygb), a novel oxygen-binding protein, is expressed in the majority of tissues and has been proposed to function in nitric oxide (NO) metabolism in the vasculature and to have cytoprotective properties. However, the overall functions of Cygb remain elusive. Cygb is also expressed in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin-and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population of Cygb neurons co-expressing nNOS. Furthermore, it was shown that the majority of neurons expressing somastostatin and vasoactive intestinal peptide also co-express Cygb and nNOS. Detailed information regarding the neurochemical phenotype of Cygb neurons in the hippocampus can be a valuable tool in determining the function of Cygb in the brain.

Distribution of Cytoglobin in the Mouse Brain

“…Noticeable are, furthermore, hippocampal pyramidal neurons with dendritic bundles in the strata oriens and radiatum and long basal processes that may represent branching axons projecting to septum, amygdala, and entorhinal cortex areas (Arszovszki et al, 2014 ). These distinctly Cygb-labeled neurons were also recently described by Hundahl et al ( 2014 ).…”

“…Most previous analyses focused on the cellular localization and the function of Cygb in cells of the supportive tissues, leading to the conclusion that modulated Cygb-expression is associated with diseases such as fibrosis or cancer (He et al, 2011 ; Oleksiewicz et al, 2013 ; Kawada, 2015 ; Thuy Le et al, 2015 ). There is, however, conclusive evidence that Cygb also resides in neurons (Schmidt et al, 2004 , 2005 ; Hundahl et al, 2010 , 2014 ). In contrast to the localization in fibroblast-related cells, Cygb was present in both, cytoplasm and nucleus of neurons.…”

Brain globins in physiology and pathology

“…Most neuronal nitric oxide synthase (nNOS)-positive neurons are found to co-localize Cygb. Hundahl et al (2014) studied neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus, revealing that nearly all the parvalbumin-and hemeoxygenase 1-positive neurons co-express Cygb, and the majority of neurons expressing somastostatin and vasoactive intestinal peptide also co-express Cygb and nNOS, therefore confirming Cygb expression in different neurons. Subcellular localizations of Cygb are cytoplasm, along neurotubuli, mitochondria and the nucleus (Schmidt et al, 2004;Hundahl et al, 2010).…”

Differential plastic changes in synthesis and binding in the mouse somatostatin system after electroconvulsive stimulation

“…SST immunofluorescence was performed as previously described with minor modifications (51). The slides were defrosted for 10 min at R T and subsequently fixed in 4% paraformaldehyde for 10 min.…”