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Transverse (left) and longitudinal (right) sections of lamprey spinal cord. Axonal fiber diameters range from 1 m in the dorsal columns to 20-40 m (Mü ller axons) in the ventral region. Glial fibers densely fill the space between axons.
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Membrane constituents may play a key role in the magnetization transfer (MT) effect. In lamprey spinal cord, axonal diameters range from <1 microm in the dorsal region to 20-40 microm in the ventral region. There is a corresponding range of axonal, and hence cell membrane, density. These characteristics permit determination of the effect of cell me...
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Glial cells in the nervous system regulate and support many functions related to neuronal activity. Understanding how the vertebrate nervous system has evolved demands a greater understanding of the mechanisms controlling evolution and development of glial cells in basal vertebrates. Among vertebrate glia, oligodendrocytes form an insulating myelin...
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... Fractional anisotropy and mean diffusivity reflect, respectively, directional (or anisotropic) motion and the average motion of water. Magnetization transfer ratio depends on the transfer of spins between free protons (in water) and bound protons (bound to macromolecules); it is believed to index macromolecules of myelin (Laule et al., 2007;Mancini et al., 2020) as well as those in the cellular membranes of neurites (Patel et al., 2019;Uematsu et al., 2004). Considering the complex cellular composition of the cerebral cortex and debates on the connection between MRI metrics and microstructural features, using multi-modality MRI may provide a chance to gain insights into the microstructural mechanism underlying the association between testosterone and the cerebral cortex. ...
The second decade of life is a critical period of transition: it involves a series of biological and psychosocial changes that are essential for learning and adaptation to adult life, as well as for the development of a healthy brain. The body of work presented in this doctoral thesis aims to investigate the maturation of the brain during puberty and the possible role of testosterone in shaping the brain; it extends what is known about the hormonal events during puberty. By integrating multi-modal datasets of brain structure and function and longitudinal data on pubertal testosterone, this thesis first revealed the relationship between pubertal testosterone and brain structure, which was modulated by the timing of the testosterone surge; an earlier peak in the change in testosterone levels predicted a stronger relationship. Then it revealed that the cumulative exposure to testosterone during puberty moderated the relationship between adult testosterone and brain response to faces. Using data acquired with functional magnetic resonance imaging (fMRI) in two large cohorts (the Avon Longitudinal Study of Parents and Children, IMAGEN) with the same face paradigm, we have also revealed robust canonical connectivity of the face network that was invariant across populations and developmental stages (i.e., from adolescence to young adulthood). When assessing this network at an individual level, connectivity profiles of individual participants deviated from the canonical one, with the magnitude of this deviation relating to the presence of psychopathology. Lastly, moving the focus from the brain to the body, we have clarified the nature of the relationship between testosterone and sex hormone-binding globulin (SHBG) and body mass index throughout puberty. Combining phenotypic and genetic data, our findings support a hypothesis that high SHBG leads to high total testosterone through a functional hypothalamic-pituitary-gonadal axis.
Taken together, these findings indicate a possible organizational effect of pubertal hormones and suggest that consideration of the organizational effects of pubertal hormones is required to reveal the complex relationship between testosterone and social cognition later in life. In addition, we suggest that the relationship between testosterone and the brain may involve multiple biological and psychosocial factors.
... FA and MD reflect, respectively, directional (or anisotropic) motion and the average motion of water. MTR depends on the transfer of spins between free protons (in water) and bound protons (bound to macromolecules); it is believed to index macromolecules of myelin (Laule et al. 2007;Mancini et al. 2020) as well as those in the cellular membranes of neurites (Uematsu et al. 2004;Patel et al. 2019). Considering the complex cellular composition of cerebral cortex and debates on the connection between MRI metrics and microstructural features, using multimodal MRI may provide a chance to gain insights of the microstructural mechanism underlying the association between testosterone and cerebral cortex. ...
Adolescence is a period of brain maturation that may involve a second wave of organizational effects of sex steroids on the brain. Rodent studies suggest that, overall, organizational effects of gonadal steroid hormones decrease from the prenatal/perinatal period to adulthood. Here we used multimodal magnetic resonance imaging to investigate whether 1) testosterone exposure during adolescence (9-17 years) correlates with the structure of cerebral cortex in young men (n = 216, 19 years of age); 2) this relationship is modulated by the timing of testosterone surge during puberty. Our results showed that pubertal testosterone correlates with structural properties of the cerebral cortex, as captured by principal component analysis of T1 and T2 relaxation times, myelin water fraction, magnetization transfer ratio, fractional anisotropy and mean diffusivity. Many of the correlations between pubertal testosterone and the cortical structure were stronger in individuals with earlier (vs. later) testosterone surge. We also demonstrated that the strength of the relationship between pubertal testosterone and cortical structure across the cerebral cortex varies as a function of inter-regional profiles of gene expression specific to dendrites, axonal cytoskeleton, and myelin. This finding suggests that the cellular substrate underlying the relationships between pubertal testosterone and cerebral cortex involves both dendritic arbor and axon.
... Historically, MTR has been used as a myelin measure within white matter (Schmierer et al., 2004), and is believed to hold the same sensitivity to myelin in cortical gray matter (Chen et al., 2013;Edwards et al., 2018;Laule et al., 2007). We should keep in mind, however, that MTR is not necessarily specific to myelin, as there may be other under-appreciated sources of signal from macromolecules, such as cellular membranes of neurites (Laule et al., 2007;Uematsu et al., 2004). Histological examinations in demyelinating mouse models fail to show a relationship between MTR and myelin content in white matter, deep gray-matter, and cortical gray-matter (Fjaer et al., 2015). ...
Neurobiology underlying inter-regional variations - across the human cerebral cortex - in measures derived with multi-modal magnetic resonance imaging (MRI) is poorly understood. Here, we characterize inter-regional variations in a large number of such measures, including T1 and T2 relaxation times, myelin water fraction (MWF), T1w/T2w ratio, mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio (MTR) and cortical thickness. We then employ a virtual-histology approach and relate these inter-regional profiles to those in cell-specific gene expression. Virtual histology revealed that most MRI-derived measures, including T1, T2 relaxation time, MWF, T1w/T2w ratio, MTR, FA and cortical thickness, are associated with expression profiles of genes specific to CA1 pyramidal cells; these genes are enriched in biological processes related to dendritic arborisation. In addition, T2 relaxation time, MWF and T1w/T2w ratio are associated with oligodendrocyte-specific gene-expression profiles, supporting their use as measures sensitive to intra-cortical myelin. MWF contributes more variance than T1w/T2w ratio to the mean oligodendrocyte expression profile, suggesting greater sensitivity to myelin. These cell-specific MRI associations may help provide a framework for determining which MRI sequences to acquire in studies with specific neurobiological hypotheses.
... We found that GFAP expression is present in radial glial cells along the neural tube, but does not appear to be expressed in cells that accompany sensory and motor axons in the developing lamprey (data not shown). A lamprey-specific monoclonal antibody, LCM29, was previously found to label keratin specific to intermediate filaments (IF) within glia, but not neurons, in larval and adult lampreys (Merrick et al., 1995;Uematsu et al., 2004;Zhang et al., 2014). We examined IF-keratin during embryogenesis (Fig. 4). ...
... While LCM29-positive IF-keratin has been shown to be glialspecific in larval and adult sea lamprey (Merrick et al., 1995;Uematsu et al., 2004;Zhang et al., 2014), its restriction to glia during embryogenesis has not been established. Since glia and axons are tightly associated, and the observed expression pattern of IF-keratin in motor roots is similar to neurofilament expression in motor axons, we determined whether IF-keratin and neurofilament localize to separate glial and neuronal cell populations respectively in developing lamprey larvae. ...
Glial cells in the nervous system regulate and support many functions related to neuronal activity. Understanding how the vertebrate nervous system has evolved demands a greater understanding of the mechanisms controlling evolution and development of glial cells in basal vertebrates. Among vertebrate glia, oligodendrocytes form an insulating myelin layer surrounding axons of the central nervous system (CNS) in jawed vertebrates. Jawless vertebrates lack myelinated axons but it is unclear when oligodendrocytes or the regulatory mechanisms controlling their development evolved. To begin to investigate the evolution of mechanisms controlling glial development, we identified key genes required for the differentiation of oligodendrocytes in gnathostomes, including Nkx2.2, SoxE genes, and PDGFR, analyzed their expression, and used CRISPR/Cas9 genome editing to perturb their functions in a primitively jawless vertebrate, the sea lamprey. We show in lamprey that orthologs required for oligodendrocyte development in jawed vertebrates are expressed in the lamprey ventral neural tube, in similar locations where gnathostome oligodendrocyte precursor cells (OPC) originate. In addition, they appear to be under the control of conserved mechanisms that regulate OPC development in jawed vertebrates and may also function in gliogenesis. Our results suggest that although oligodendrocytes first emerged in jawed vertebrates, regulatory mechanisms required for their development predate the divergence of jawless and jawed vertebrates.
... The mouse monoclonal antibody against sea lamprey glial cytokeratin (LCM 29) has been previously characterized (Merrick et al., 1995) and used in studies about the spinal cord of sea lamprey (Lurie et al., 1994;Uematsu et al., 2004;Vidal Pizarro et al., 2004;Fernández-López et al., 2014). ...
Despite the importance of doublecortin (DCX) for the development of the nervous system, its expression in the retina of most vertebrates is still unknown. The key phylogenetic position of lampreys, together with their complex life cycle, with a long blind larval stage and an active predator adult stage, makes them an interesting model to study retinal development. Here, we studied the spatiotemporal pattern of expression of DCX in the retina of the sea lamprey. In order to characterize the DCX expressing structures, the expression of acetylated α-tubulin (a neuronal marker) and cytokeratins (glial marker) was also analyzed. Tract-tracing methods were used to label ganglion cells. DCX immunoreactivity appeared initially in photoreceptors, ganglion cells and in fibers of the prolarval retina. In larvae smaller than 100 mm, DCX expression was observed in photoreceptors, in cells located in the inner nuclear and inner plexiform layers and in fibers coursing in the nuclear and inner plexiform layers, and in the optic nerve. In retinas of premetamorphic and metamorphic larvae, DCX immunoreactivity was also observed in radially oriented cells and fibers and in a layer of cells located in the outer part of the inner neuroblastic layer of the lateral retina. Photoreceptors and fibers ending in the outer limitans membrane showed DCX expression in adults. Some retinal pigment epithelium cells were also DCX immunoreactive. Immunofluorescence for α-tubulin in premetamorphic larvae showed coexpression in most of the DCX immunoreactive structures. No cells/fibers were found showing DCX and cytokeratins colocalization. The perikaryon of mature ganglion cells is DCX negative. The expression of DCX in sea lamprey retinas suggests that it could play roles in the migration of cells that differentiate in the metamorphosis, in the establishment of connections of ganglion cells and in the development of photoreceptors. Our results also suggest that the radial glia and retinal pigment epithelium cells of lampreys are neurogenic. Comparison of our observations with those reported in gnathostomes reveals similarities and interesting differences probably due to the peculiar development of the sea lamprey retina.
... The mouse monoclonal anti-cytokeratin antibody (LCM 29) is a lamprey specific antibody that has been previously characterized (Merrick et al., 1995) and used in studies about the spinal cord of lampreys (Lurie et al., 1994;Uematsu et al., 2004;Vidal Pizarro et al., 2004). ...
In contrast to mammals, the spinal cord of lampreys spontaneously recovers from a complete spinal cord injury (SCI). Understanding the differences between lampreys and mammals in their response to SCI could provide valuable information to propose new therapies. Unique properties of the astrocytes of lampreys probably contribute to the success of spinal cord regeneration. The main aim of our study was to investigate, in the sea lamprey, the release of aminoacidergic neurotransmitters and the subsequent astrocyte uptake of these neurotransmitters during the first week following a complete SCI by detecting glutamate, GABA, glycine, Hu and cytokeratin immunoreactivities. This is the first time that aminoacidergic neurotransmitter release from neurons and the subsequent astrocytic response after SCI are analysed by immunocytochemistry in any vertebrate. Spinal injury caused the immediate loss of glutamate, GABA and glycine immunoreactivities in neurons close to the lesion site (except for the cerebrospinal fluid-contacting GABA cells). Only after SCI, astrocytes showed glutamate, GABA and glycine immunoreactivity. Treatment with an inhibitor of glutamate transporters (DL-TBOA) showed that neuronal glutamate was actively transported into astrocytes after SCI. Moreover, after SCI, a massive accumulation of inhibitory neurotransmitters around some reticulospinal axons was observed. Presence of GABA accumulation significantly correlated with a higher survival ability of these neurons. Our data show that, in contrast to mammals, astrocytes of lampreys have a high capacity to actively uptake glutamate after SCI. GABA may play a protective role that could explain the higher regenerative and survival ability of specific descending neurons of lampreys. GLIA 2014
