Adult neurogenesis and gliogenesis in the dorsal and ventral canine hippocampus

Abstract

Dentate gyrus (DG) of the mammalian hippocampus gives rise to new neurons and astrocytes all through adulthood. Canine hippocampus presents many similarities in fetal development, anatomy, and physiology with human hippocampus, establishing canines as excellent animal models for the study of adult neurogenesis. In the present study, BrdU‐dated cells of the structurally and functionally dissociated dorsal (dDG) and ventral (vDG) adult canine DG were comparatively examined over a period of 30 days. Each part's neurogenic potential, radial glia‐like neural stem cells (NSCs) proliferation and differentiation, migration, and maturation of their progenies were evaluated at 2, 5, 14, and 30 days post BrdU administration, with the use of selected markers (glial fibrillary acidic protein, doublecortin, calretinin and calbindin). Co‐staining of BrdU+ cells with NeuN or S100B permitted the parallel study of the ongoing neurogenesis and gliogenesis. Our findings reveal the comparatively higher populations of residing granule cells, proliferating NSCs and BrdU+ neurons in the dDG, whereas newborn neurons of the vDG showed a prolonged differentiation, migration, and maturation. Newborn astrocytes were found all along the dorso‐ventral axis, counting however for only 11% of newborn cell population. Comparative evaluation of adult canine and rat neurogenesis revealed significant differences in the distribution of resident and newborn granule cells along the dorso‐ventral axis, division pattern of adult NSCs, maturation time plan of newborn neurons, and ongoing gliogenesis. Concluding, spatial and temporal features of adult canine neurogenesis are similar to that of other gyrencephalic species, including humans, and justify the comparative examination of adult neurogenesis across mammalian species.

Birth and death of neurons in the developing and mature mammalian brain

“…Electrophysiological studies showed the rapid loss of immature neuronal properties, while immediate-early genes (Arc) expression profiles revealed an earlier neuronal activity of the septal neurons. Our marker expression studies support this notion by showing that newborn neurons of the septal DG showed an earlier expression of neuronal markers (DCX, NeuN) and an earlier acquisition of glutamate receptors (NMDA R1 and GluR2), in both the rat and canine DG (Bekiari et al, 2015a;Bekiari et al, 2020). Notably, there was a profound delay in the maturation time of adult-born neurons of the canine DG compared to the rat DG, which was anticipated by similar findings in other gyrencephalic species, such as the sheep and non-human primates.…”

“…However, when we performed a parallel stereological analysis of the newborn BrdU + cells and the total granule cell populations of the two dentate parts in the rat hippocampus we found an equal neurogenic potential of the septal and temporal part (Bekiari et al, 2015a). In the adult canine DG, however, similar stereological counting revealed an increased neurogenic potential of the septal DG part, which was attributed to the higher number of locally dividing radial glia-like NSCs (Bekiari et al, 2020). In both mammalian species studied, the developmentally 'older' temporal DG part showed an increased potential for viability of newborn neurons, achieving a balance between the birth rate of new-neurons and their accession into the local neuronal circuits.…”

“…In a detailed study, we provided a description of the cellular and temporal characteristics of the sequential steps of neurogenesis in the adult canine hippocampus. Based on the evaluation of these data in conjunction with reports on the adult rodent and non-human primate DG neurogenesis, we assumed that dynamic changes in the numbers of canine proliferating radial glia-like NSCs and adult-born granule cells closely resemble these of other gyrencephalic species, although, to some extent, they also bear similarities with features of adult rat DG neurogenesis (Bekiari et al, 2020).…”

Neural Differentiation of Human Dental Mesenchymal Stem Cells Induced by ATRA and UDP-4: A Comparative Study

“…Cells stained red for GFAP and green for NeuN were visualized and examined under a fluorescent microscope. Information for the antibody characterization was derived from the published work of Bekiari et al (2020) [ 25 ]. GFAP is an intracytoplasmic filamentous protein of astrocytes, proven to be a specific marker of cells of astrocyte origin, as the radial glia-like neural stem cells of the adult brain [ 26 ].…”

Significance of mitochondrial activity in neurogenesis and neurodegenerative diseases

“…Neurogenesis is a relatively new concept in neuroscience. The prevailing thought, based on canine and rodent adult models, is neurogenesis occurs in the dentate gyrus of the human adult hippocampus, and the subventricular (Spalding et al, 2013;Toda and Gage, 2018;Bekiari et al, 2020). NSC in these zones, can transition between quiescent and active states (Mohammad et al, 2019).…”