Distribution of Cytoglobin in the Mouse Brain

Abstract

Cytoglobin (Cygb) is a vertebrate globin with so far poorly defined function. It is expressed in the fibroblast cell-lineage but has also been found in neurons. Here we provide, using immunohistochemistry, a detailed study on the distribution of Cygb in the mouse brain. While Cygb is a cytoplasmic protein in active cells of the supportive tissue, in neurons it is located in the cytoplasm and the nucleus. We found the expression of Cygb in all brain regions, although only a fraction of the neurons was Cygb-positive. Signals were of different intensity ranging from faint to very intense. Telencephalic neurons in all laminae of the cerebral cortex (CCo), in the olfactory bulb (in particular periglomerular cells), in the hippocampal formation (strongly stained pyramidal cells with long processes), basal ganglia (scattered multipolar neurons in the dorsal striatum, dorsal and ventral pallidum (VP)), and in the amygdala (neurons with unlabeled processes) were labeled by the antibody. In the diencephalon, we observed Cygb-positive neurons of moderate intensity in various nuclei of the dorsal thalamus, in the hypothalamus, metathalamus (geniculate nuclei), epithalamus with strong labeling of habenular nucleus neurons and no labeling of pineal cells, and in the ventral thalamus. Tegmental neurons stood out by strongly stained somata with long processes in, e.g., the laterodorsal nucleus. In the tectum, faintly labeled neurons and fibers were detected in the superior colliculus (SC). The cerebellum exhibited unlabeled Purkinje-neurons but signs of strong afferent cortical innervation. Neurons in the gray matter of the spinal cord showed moderate immunofluorescence. Peripheral ganglia were not labeled by the antibody. The Meynert-fascicle and the olfactory and optic nerves/tracts were the only Cygb-immunoreactive (Cygb-IR) fiber systems. Notably, we found a remarkable level of colocalization of Cygb and neuronal nitric oxide (NO)-synthase in neurons, which supports a functional association.

Strong modulation of nitrite reductase activity of cytoglobin by disulfide bond oxidation: Implications for nitric oxide homeostasis

“…Although more studies are required to explore the role of NiR activity in cells, we can speculate that the NO generating activity of Cygb can be controlled through the oxidation of the surface exposed cysteines, enhancing NO production under conditions such as oxidative stress. Recently Cygb has been found to be co-localised with nNOS in various areas of the mouse brain, expressed in the cytoplasm of neurons [31] and downregulation of Cygb prevents angiotensin-mediated hypertension [33]. This illustrates the proposition that Cygb, like Ngb, is involved in NO homeostasis.…”

“…Additionally, the co-localisation of Cygb with neuronal NO synthase in the brain strongly supports a link between Cygb and NO metabolism [31], as does the protection of Cygb against hepatocyte damage during inflammation [32] and the angiotensin-mediated hypertension in aortic smooth muscle cells [33]. Knockout of Cygb in mice prolongs NO decay in aortic cells and that NO metabolism in vascular smooth muscle regulates NO flux [33].…”

Modeling Vestibular Compensation: Neural Plasticity Upon Thalamic Lesion

“…Studies of "central vestibular transmission" actually identified dopaminergic, serotonergic, nitrergic, and amino-acidergic transmitter systems of the VN [cf. (96)(97)(98)] while subcortical and cortical structures of the pathways upstream to the VN are less well-defined in terms of neurochemistry. However, many thalamic and cortical regions are multisensory and multimodal and thus may use various neuroactive substances for transmission.…”

Evaluation of globins expression in brain, heart, and lung in rats exposed to side stream cigarette smoke

“…They have all determinant key roles stored in their sequences for O 2 transport function, protecting several tissues against falls in O 2 partial pressure (Sun et al, ; Khan et al, ; Li et al, ; Burmester & Hankeln, 2014). In rats and mice, Cygb and Ngb are expressed in most brain neurons, but apparently are not expressed in glial cells (Moens & Dewilde, 2000; Burmester & Hankeln, 2014; Reuss et al, ). Some studies have shown differences in gene and protein expression of Ngb in brain tissue, as it has been more expressed in the cerebral cortex, hippocampus, hypothalamus and cerebellum (Hundahl et al, ; Hundahl et al, ).…”