Mechanical Brain Injury Increases Cells’ Production of Cystathionine β-Synthase and Glutamine Synthetase, but Reduces Pax2 Expression in the Telencephalon of Juvenile Chum Salmon, Oncorhynchus keta

Abstract

The considerable post-traumatic brain recovery in fishes makes them a useful model for studying the mechanisms that provide reparative neurogenesis, which is poorly represented in mammals. After a mechanical injury to the telencephalon in adult fish, lost neurons are actively replaced due to the proliferative activity of neuroepithelial cells and radial glia in the neurogenic periventricular zone. However, it is not enough clear which signaling mechanisms are involved in the activation of adult neural stem cells (aNSC) after the injury (reactive proliferation) and in the production of new neurons (regenerative neurogenesis) from progenitor cells (NPC). In juvenile Pacific salmon, the predominant type of NSCs in the telencephalon are neuroepithelial cells corresponding to embryonic NSCs. Expression of glutamine synthetase (GS), a NSC molecular marker, was detected in the neuroepithelial cells of the pallium and subpallium of juvenile chum salmon, Oncorhynchus keta. At 3 days after a traumatic brain injury (TBI) in juvenile chum salmon, the GS expression was detected in the radial glia corresponding to aNSC in the pallium and subpallium. The maximum density of distribution of GS+ radial glia was found in the dorsal pallial region. Hydrogen sulfide (H2S) is a proneurogenic factor that reduces oxidative stress and excitotoxicity effects, along with the increased GS production in the brain cells of juvenile chum salmon. In the fish brain, H2S producing by cystathionine β-synthase in neurogenic zones may be involved in maintaining the microenvironment that provides optimal conditions for the functioning of neurogenic niches during constitutive neurogenesis. After injury, H2S can determine cell survivability, providing a neuroprotective effect in the area of injury and reducing the process of glutamate excitotoxicity, acting as a signaling molecule involved in changing the neurogenic environment, which leads to the reactivation of neurogenic niches and cell regeneration programs. The results of studies on the control of the expression of regulatory Sonic Hedgehog genes (Shh) and the transcription factors Paired Box2 (Pax2) regulated by them are still insufficient. A comparative analysis of Pax2 expression in the telencephalon of intact chum salmon showed the presence of constitutive patterns of Pax2 expression in neurogenic areas and non-neurogenic parenchymal zones of the pallium and subpallium. After mechanical injury, the patterns of Pax2 expression changed, and the amount of Pax2+ decreased (p < 0.05) in lateral (Dl), medial (Dm) zones of the pallium, and the lateral zone (Vl) of the subpallium compared to the control. We believe that the decrease in the expression of Pax2 may be caused by the inhibitory effect of the Pax6 transcription factor, whose expression in the juvenile salmon brain increases upon injury.

Molecular Markers of Adult Neurogenesis in the Telencephalon and Tectum of Rainbow Trout, Oncorhynchus mykiss

“…Studies on the medaka, Oryzias latipes, and the zebrafish, Danio rerio, have also shown that, within proliferative populations in the optic tectum, aNSCs are indeed NE-like stem/progenitor cells, but not RG cells [20,21]. Similar results were obtained in other studies, in particular, on the optic tectum [22] and telencephalon [23]. The study of the lateral zebrafish pallium revealed a population of adult NE cells [24,25] maintained from an early to various postembryonic stages of ontogenesis.…”

“…In trout, RG cells often formed clusters separated by immunonegative regions in the marginal zone (Figure 2B,D). The presence of GS+ RG cells was revealed also in other fish species such as Apteronotus albifrons [34], the zebrafish [67], and the chum salmon O. keta [23]. Tectal glia have been described as "tanycytes" from the ocean sunfish, Mola mola [68]; however, cells of this type in the goldfish, Carassius auratus, were referred to as "radial glia" [69], and in L. macrochirus and P. nebulifer as "ependymoglia" [70].…”

ILB®, a Low Molecular Weight Dextran Sulphate, Restores Glutamate Homeostasis, Amino Acid Metabolism and Neurocognitive Functions in a Rat Model of Severe Traumatic Brain Injury

“…The drug treatment also diminished the sTBI-mediated increase in brain L-Cystat and normalized the level of SAH. Although obtained in a fish model of TBI, it was found that head trauma causes an increase in the expression of the L-Cystat synthesizing enzyme (L-cystathione-β-synthase) in the post-injured brain [ 39 ], thereby possibly explaining the 1.9 and 1.7-fold increase in L-Cystat we found in sTBI rats at 2 and 7 days post-impact, respectively. On the other hand, since the precursor of GSH biosynthesis (L-cysteine) originates from the enzymatic scission of L-Cystat, the increased levels of L-Cystat following sTBI may be causative of a decreased rate of GSH biosynthesis due to decreased L-cysteine availability.…”

Expression of Doublecortin, Glial Fibrillar Acidic Protein, and Vimentin in the Intact Subpallium and after Traumatic Injury to the Pallium in Juvenile Salmon, Oncorhynchus masou

“…Neuroepithelial cells play an essential role in mammalian embryonic neurogenesis, while glial stem cells are the main source of neurons at the postembryonic stages of development [27]. In contrast to mammals, neuroepithelial-like (NE) stem/progenitor cells are present in the brain of fish throughout life [27][28][29].…”