Abstract
Fish are a convenient model for the study of reparative and post-traumatic processes of central nervous system (CNS) recovery, because the formation of new cells in their CNS continues throughout life. After a traumatic injury to the cerebellum of juvenile masu salmon, Oncorhynchus masou, the cell composition of the neurogenic zones containing neural stem cells (NSCs)/neural progenitor cells (NPCs) in the acute period (two days post-injury) changes. The presence of neuroepithelial (NE) and radial glial (RG) neuronal precursors located in the dorsal, lateral, and basal zones of the cerebellar body was shown by the immunohistochemical (IHC) labeling of glutamine synthetase (GS). Progenitors of both types are sources of neurons in the cerebellum of juvenile O. masou during constitutive growth, thus, playing an important role in CNS homeostasis and neuronal plasticity during ontogenesis. Precursors with the RG phenotype were found in the same regions of the molecular layer as part of heterogeneous constitutive neurogenic niches. The presence of neuroepithelial and radial glia GS+ cells indicates a certain proportion of embryonic and adult progenitors and, obviously, different contributions of these cells to constitutive and reparative neurogenesis in the acute post-traumatic period. Expression of nestin and vimentin was revealed in neuroepithelial cerebellar progenitors of juvenile O. masou. Patterns of granular expression of these markers were found in neurogenic niches and adjacent areas, which probably indicates the neurotrophic and proneurogenic effects of vimentin and nestin in constitutive and post-traumatic neurogenesis and a high level of constructive metabolism. No expression of vimentin and nestin was detected in the cerebellar RG of juvenile O. masou. Thus, the molecular markers of NSCs/NPCs in the cerebellum of juvenile O. masou are as follows: vimentin, nestin, and glutamine synthetase label NE cells in intact animals and in the post-traumatic period, while GS expression is present in the RG of intact animals and decreases in the acute post-traumatic period. A study of distribution of cystathionine β-synthase (CBS) in the cerebellum of intact young O. masou showed the expression of the marker mainly in type 1 cells, corresponding to NSCs/NCPs for other molecular markers. In the post-traumatic period, the number of CBS+ cells sharply increased, which indicates the involvement of H2S in the post-traumatic response. Induction of CBS in type 3 cells indicates the involvement of H2S in the metabolism of extracellular glutamate in the cerebellum, a decrease in the production of reactive oxygen species, and also arrest of the oxidative stress development, a weakening of the toxic effects of glutamate, and a reduction in excitotoxicity. The obtained results allow us to consider H2S as a biologically active substance, the numerous known effects of which can be supplemented by participation in the processes of constitutive neurogenesis and neuronal regeneration.
Highlights
Fish are a convenient model for studying the reparative and post-traumatic central nervous system (CNS recovery), because the formation of new cells in their CNS continues throughout their life [1]
The IHC labeling of vimentin was detected in the dorsal zone (DZ), lateral zone (LZ), and basal zone (BZ) of the cerebellar body, and in granular eminences
In the acute post-traumatic period, we observed a significant increase in Nes+ cells in all areas of the juvenile O. masou cerebellum, a rearrangement and reorganization of constitutive patterns of nestin immunolocalization, an increase in patterns of granular nestin immunoexpression in the molecular layer, and numerous radial and tangential patterns of post-traumatic cell migration
Summary
Fish are a convenient model for studying the reparative and post-traumatic central nervous system (CNS recovery), because the formation of new cells in their CNS continues throughout their life [1]. Salmonids, which are a phylogenetically ancient group, have a high concentration of undifferentiated elements, both in the matrix zones of the brain and in the parenchyma [11] Their ontogenesis is characterized by such phenomena as developmental delay and retention of signs of the embryonic organization of CNS which occur at the stage of active brain growth, where the morphogenesis processes are most clearly and fully expressed [11]. This feature of salmon CNS development, referred to as embrionalization, is confirmed by the presence of a large number of embryonic neuronal stem cells (NSCs) corresponding to cells of the neuroepithelial (NE) type, as well as radial glial (RG) cells corresponding to adult progenitors [12,13,14,15]
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