In the adult mammalian nervous system most neurons are not renewed or replaced throughout the animal life. An exception is represented by adult neurogenesis, the birth of new neurons from stem cell niches of the mature brain. Adult neurogenesis is highly reduced from fish to mammals, and, to a lesser extent, among mammals, especially considering large-brained, gyrencephalic species with respect to rodents. Recently, a novel type of plasticity is emerging: the so-called ¿immature¿ neurons, which are generated during embryogenesis, then continuing to express markers of immaturity during adulthood (e.g., doublecortin; DCX). These cells were first described in the cerebral cortex of rodents, wherein they are restricted to the layer II of the paleocortex. Subsequent reports observed them also in neocortex and subcortical regions of some mammals, yet, the current knowledge about the function of immature neurons is highly fragmentary. We know they progressively mature with age, but it is far from clear their possible integration into neural circuits. Due to a lack of comparable, systematic studies (most analyses are qualitative and conducted in single animal species), their phylogenetic distribution remains obscure. The present study was conceived to characterize and quantify immature neurons in a comparable way within two brain regions (cortex and amygdala) of four mammalian species (i.e. cat, chimpanzee, marmoset and mouse) endowed with different brain size and gyrencephaly. This objective was addressed by detecting the cytoskeletal protein DCX (a marker typically associated with structural plasticity and immaturity) along with other markers of cell proliferation and differentiation, revealed by single-to-triple staining in light and confocal microscopy, and by quantifying the cells with Neurolucida software (linear density in cortical layer II, quadratic density in the amygdala). The aim is to compare the pattern of distribution and the amount of immature neurons in cortical and subcortical areas of the different species and to discuss them in the context of a larger study (ongoing in our lab) involving 12 mammalian species. Considering the cortex, a high difference in terms of DCX+ cell linear density was found in the neocortex of the animal species considered: whereas substantially no cells were detectable in mice, and low amount in marmosets, a consistent number was observed in the large, gyrencephalic brains (cat and chimpanzee; as much as one order of magnitude). Moreover, data do not indicate a strong link between occurrence of immature neurons and specific functional cortical areas. Aside from cell density, other features investigated here (morphology, occurrence of cell types, degree of maturity/immaturity, non-proliferative state) were substantially similar regardless of the species considered, Preliminary data obtained in the amygdala, showed the presence of large amounts of immature neurons in cat, marmoset and chimpanzee, and virtually no immature cells in mouse. Areal density values were higher in marmoset with respect to cat. In general, it appears that species hosting the immature neurons in the whole cerebral cortex also have consistent numbers in the amygdala. These preliminary results seem to confirm that immature neurons would be more abundant in large-brained species also considering subcortical structures. In conclusion, this study indicates that immature neurons are widely distributed and more abundant in large-brain
Neuroni immaturi nella corteccia cerebrale e nell'amigdala in quattro specie di mammiferi
CAVALLO, FRANCESCA
2018/2019
Abstract
In the adult mammalian nervous system most neurons are not renewed or replaced throughout the animal life. An exception is represented by adult neurogenesis, the birth of new neurons from stem cell niches of the mature brain. Adult neurogenesis is highly reduced from fish to mammals, and, to a lesser extent, among mammals, especially considering large-brained, gyrencephalic species with respect to rodents. Recently, a novel type of plasticity is emerging: the so-called ¿immature¿ neurons, which are generated during embryogenesis, then continuing to express markers of immaturity during adulthood (e.g., doublecortin; DCX). These cells were first described in the cerebral cortex of rodents, wherein they are restricted to the layer II of the paleocortex. Subsequent reports observed them also in neocortex and subcortical regions of some mammals, yet, the current knowledge about the function of immature neurons is highly fragmentary. We know they progressively mature with age, but it is far from clear their possible integration into neural circuits. Due to a lack of comparable, systematic studies (most analyses are qualitative and conducted in single animal species), their phylogenetic distribution remains obscure. The present study was conceived to characterize and quantify immature neurons in a comparable way within two brain regions (cortex and amygdala) of four mammalian species (i.e. cat, chimpanzee, marmoset and mouse) endowed with different brain size and gyrencephaly. This objective was addressed by detecting the cytoskeletal protein DCX (a marker typically associated with structural plasticity and immaturity) along with other markers of cell proliferation and differentiation, revealed by single-to-triple staining in light and confocal microscopy, and by quantifying the cells with Neurolucida software (linear density in cortical layer II, quadratic density in the amygdala). The aim is to compare the pattern of distribution and the amount of immature neurons in cortical and subcortical areas of the different species and to discuss them in the context of a larger study (ongoing in our lab) involving 12 mammalian species. Considering the cortex, a high difference in terms of DCX+ cell linear density was found in the neocortex of the animal species considered: whereas substantially no cells were detectable in mice, and low amount in marmosets, a consistent number was observed in the large, gyrencephalic brains (cat and chimpanzee; as much as one order of magnitude). Moreover, data do not indicate a strong link between occurrence of immature neurons and specific functional cortical areas. Aside from cell density, other features investigated here (morphology, occurrence of cell types, degree of maturity/immaturity, non-proliferative state) were substantially similar regardless of the species considered, Preliminary data obtained in the amygdala, showed the presence of large amounts of immature neurons in cat, marmoset and chimpanzee, and virtually no immature cells in mouse. Areal density values were higher in marmoset with respect to cat. In general, it appears that species hosting the immature neurons in the whole cerebral cortex also have consistent numbers in the amygdala. These preliminary results seem to confirm that immature neurons would be more abundant in large-brained species also considering subcortical structures. In conclusion, this study indicates that immature neurons are widely distributed and more abundant in large-brainFile | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14240/100527