scholarly journals Microglial MorphOMICs unravel region- and sex-dependent morphological phenotypes from postnatal development to degeneration

2021 ◽  
Author(s):  
Gloria Colombo ◽  
Ryan John Abat Cubero ◽  
Lida Kanari ◽  
Alessandro Venturino ◽  
Rouven Schulz ◽  
...  
Keyword(s):  
Brain Regions ◽  
Adult Brain ◽  
Topological Data Analysis ◽  
Environmental Cues ◽  
Sexually Dimorphic ◽  
Biological Variability ◽  
Physiological Conditions ◽  
Distinct Cluster ◽  
Morphometric Features ◽  
Morphological Phenotype

Microglia contribute to tissue homeostasis in physiological conditions with environmental cues influencing their ever-changing morphology. Strategies to identify these changes usually involve user-selected morphometric features, which, however, have proved ineffective in establishing a spectrum of context-dependent morphological phenotypes. Here, we have developed MorphOMICs, a topological data analysis approach to overcome feature-selection-based biases and biological variability. We extracted a spatially heterogeneous and sexually-dimorphic morphological phenotype for seven adult brain regions, with ovariectomized females forming their own distinct cluster. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration models, 5xFAD and CK-p25. Females show an earlier morphological shift in the immediately-affected brain regions. Finally, we demonstrate that both the primary- and the short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs maps microglial morphology into a spectrum of cue-dependent phenotypes in a minimally-biased and semi-automatic way.

scholarly journals Activation of a neural stem cell transcriptional program in parenchymal astrocytes

2020 ◽  
Author(s):  
Jens P. Magnusson ◽  
Margherita Zamboni ◽  
Giuseppe Santopolo ◽  
Jeff E. Mold ◽  
Mauricio Barrientos-Somarribas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Brain Regions ◽  
Adult Brain ◽  
Targeted Interventions ◽  
Physiological Conditions ◽  
Neuronal Lineage ◽  
Epidermal Growth

AbstractNeural stem cells, located in discrete niches in the adult brain, generate new neurons throughout life. These stem cells are specialized astrocytes, but astrocytes in other brain regions do not generate neurons under physiological conditions. After stroke, however, striatal astrocytes undergo neurogenesis in mice, triggered by decreased Notch signaling. We used single-cell RNA sequencing to characterize neurogenesis by Notch-depleted striatal astrocytes in vivo. Striatal astrocytes were located upstream of neural stem cells in the neuronal lineage. As astrocytes initiated neurogenesis, they became transcriptionally very similar to subventricular zone stem cells and progressed through a nearly identical neurogenic program. Surprisingly, in the non- neurogenic cortex, Notch-depleted astrocytes also initiated neurogenesis. Yet, the cortical astrocytes, and many striatal ones, stalled before entering transit- amplifying divisions. Infusion of epidermal growth factor enabled stalled striatal astrocytes to resume neurogenesis. We conclude that parenchymal astrocytes are latent neural stem cells and that targeted interventions can guide them through their neuronal differentiation.

scholarly journals Expression of dlx genes in the normal and regenerating brain of adult zebrafish

2020 ◽  
Author(s):  
Hellen Weinschutz Mendes ◽  
Mariam Taktek ◽  
Thomas Duret ◽  
Marc Ekker
Keyword(s):  
Nervous System ◽  
Brain Regions ◽  
Gabaergic Neurons ◽  
Adult Brain ◽  
Adult Zebrafish ◽  
Zebrafish Brain ◽  
Physiological Conditions ◽  
Inhibitory Function ◽  
Brain Regeneration ◽  
Dlx Genes

AbstractDysfunctions in the GABAergic system lead to various pathological conditions and impaired inhibitory function is one of the causes behind neuropathies characterized by neuronal hyper excitability. The Dlx homeobox genes are involved in the development of nervous system, neural crest, brachial arches and developing appendages. Dlx genes also take part in neuronal migration and differentiation during development, more precisely, in the migration and differentiation of GABAergic neurons. Functional analysis of dlx genes has mainly been carried out in developing zebrafish embryos and larvae; however information regarding the expression and roles of these genes in the adult zebrafish brain is still lacking. The extensive neurogenesis that takes place in the brain of adult zebrafish makes them a good model for the visualization of mechanisms involving dlx genes during adulthood in physiological conditions and during regeneration of the nervous system. We have identified the adult brain regions where transcripts of dlx1a, dlx2a, dlx5a and dlx6a genes are normally found and have confirmed that within telencephalic domains, there is high overlapping expression of the four dlx paralogs with a marker for GABAergic neurons. Co-localization analyses carried with the Tg(dlx6a-1.4kbdlx5a/dlx6a:GFP) reporter line have also shown that in some areas of the diencephalon, cells expressing the dlx5a/6a bigene may have a neural stem cell identity by co-localizing with a Sox2 antibody. Furthermore, investigations in a response to stab wound lesions, have demonstrated a possible participation of the dlx5a/6a bigene, most likely, of dlx5a during the regeneration of the adult zebrafish brain. These data suggest a possible participation of dlx-expressing cells during brain regeneration in adult zebrafish and also provide information on the role of dlx genes under normal physiological conditions in adults.

scholarly journals An architectonic type principle in the development of laminar patterns of cortico-cortical connections

2021 ◽  
Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag
Keyword(s):  
Structural Connectivity ◽  
Macaque Monkey ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Cortical Connections ◽  
Cortical Projections ◽  
Structural Connections ◽  
High Degree ◽  
The Brain

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.

scholarly journals Quantitative RT-PCR analyses of five evolutionary conserved genes in Alligator brains during development

2011 ◽  
Vol 2 (4) ◽  
Author(s):  
Sarah Wilson ◽  
Tianli Zhu ◽  
Rajesh Khanna ◽  
Michael Pritz
Keyword(s):  
Gene Expression ◽  
Brain Area ◽  
Brain Regions ◽  
Adult Brain ◽  
Time Interval ◽  
Conserved Genes ◽  
Mrna Gene ◽  
Alligator Mississipiensis ◽  
Mrna Gene Expression ◽  
Present Gene

AbstractGene expression was investigated in the major brain subdivisions (telencephalon, diencephalon, midbrain and hindbrain) in a representative reptile, Alligator mississipiensis, during the later stages of embryonic development. The following genes were examined: voltage-gated sodium channel isoforms: NaV1.1 and NaV1.2; synaptic vesicle 2a (SV2a); synaptophysin; and calbindin 2. With the exception of synaptophysin, which was only expressed in the telencephalon, all genes were expressed in all brain regions sampled at the time periods examined. For NaV1.1, gene expression varied according to brain area sampled. When compared with NaV1.1, the pattern of NaV1.2 gene expression differed appreciably. The gene expression of SV2a was the most robust of any of the genes examined. Of the other genes examined, although differences were noted, no statistically significant changes were found either between brain part or time interval. Although limited, the present analysis is the first quantitative mRNA gene expression study in any reptile during development. Together with future experiments of a similar nature, the present gene expression results should determine which genes are expressed in major brain areas at which times during development in Alligator. When compared with other amniotes, these results will prove useful for determining how gene expression during development influences adult brain structure.

The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia

2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Feeding Behavior ◽  
Critical Role ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Male And Female ◽  
Female Mice ◽  
Bidirectional Regulation ◽  
Fear And Anxiety ◽  
Agouti Related Protein

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.

scholarly journals Relationships between dietary macronutrients and adult neurogenesis in the regulation of energy metabolism – CORRIGENDUM

2013 ◽  
Vol 111 (4) ◽  
pp. 755-755
Author(s):  
Marianne A. Yon ◽  
Suzanna L. Mauger ◽  
Lucy C. Pickavance
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Adult Neurogenesis ◽  
Brain Regions ◽  
The Body ◽  
Adult Brain ◽  
Metabolic Dysfunction ◽  
Neurogenic Niche ◽  
Normal Limits ◽  
Simple Carbohydrates

Of the environmental factors which have an impact on body weight, nutrients are most influential. Within normal limits, hypothalamic and related neuronal populations correct perturbations in energy metabolism, to return the body to its nutritional set-point, either through direct response to nutrients or indirectly via peripheral appetite signals. Excessive intake of certain macronutrients, such as simple carbohydrates and SFA, can lead to obesity and attendant metabolic dysfunction, also reflected in alterations in structural plasticity, and, intriguingly, neurogenesis, in some of these brain regions. Neurogenesis, previously thought to occur only in the embryo, is now known to take place in the adult brain, dependent on numerous stimulating and inhibiting factors, including dietary components. Because of classic associations between neurogenesis and the hippocampus, in learning and cognition, this brain region has also been the focus of attention in the study of links between diet and neurogenesis. Recently, however, a more complete picture of this relationship has been building: not only has the hypothalamus been shown to satisfy the criteria for a neurogenic niche, but appetite-related mediators, including circulating hormones, such as leptin and ghrelin, pro-inflammatory cytokines and the endocannabinoid intracellular messengers, are also being examined for their potential role in mediating neurogenic responses to macronutrients. The present review draws together these observations and investigates whether n-3 PUFA may exert their attenuating effects on body weight through the stimulation of adult neurogenesis. Exploration of the effects of nutraceuticals on neurogenic brain regions may encourage the development of new rational therapies in the fight against obesity.

scholarly journals Topological Segmentation of Time-Varying Functional Connectivity Highlights the Role of Preferred Cortical Circuits

2020 ◽  
Author(s):  
Jacob Billings ◽  
Manish Saggar ◽  
Shella Keilholz ◽  
Giovanni Petri
Keyword(s):  
Functional Connectivity ◽  
Brain Function ◽  
Persistent Homology ◽  
Brain Regions ◽  
Topological Data Analysis ◽  
Time Varying ◽  
Imaging Data ◽  
Experimental Conditions ◽  
Common Time ◽  
Brain Imaging Data

Functional connectivity (FC) and its time-varying analogue (TVFC) leverage brain imaging data to interpret brain function as patterns of coordinating activity among brain regions. While many questions remain regarding the organizing principles through which brain function emerges from multi-regional interactions, advances in the mathematics of Topological Data Analysis (TDA) may provide new insights into the brain’s spontaneous self-organization. One tool from TDA, “persistent homology”, observes the occurrence and the persistence of n-dimensional holes presented in the metric space over a dataset. The occurrence of n-dimensional holes within the TVFC point cloud may denote conserved and preferred routes of information flow among brain regions. In the present study, we compare the use of persistence homology versus more traditional TVFC metrics at the task of segmenting brain states that differ across a common time-series of experimental conditions. We find that the structures identified by persistence homology more accurately segment the stimuli, more accurately segment volunteer performance during experimentally defined tasks, and generalize better across volunteers. Finally, we present empirical and theoretical observations that interpret brain function as a topological space defined by cyclic and interlinked motifs among distributed brain regions, especially, the attention networks.

scholarly journals The Antennal Pathway of Dragonfly Nymphs, from Sensilla to the Brain

Insects ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 886
Author(s):  
Silvana Piersanti ◽  
Manuela Rebora ◽  
Gianandrea Salerno ◽  
Sylvia Anton
Keyword(s):  
Brain Structure ◽  
Antennal Lobe ◽  
Sensory Information ◽  
Brain Structures ◽  
Brain Regions ◽  
Adult Brain ◽  
Published Data ◽  
Antennal Sensilla ◽  
Aquatic Life ◽  
The Brain

Dragonflies are hemimetabolous insects, switching from an aquatic life style as nymphs to aerial life as adults, confronted to different environmental cues. How sensory structures on the antennae and the brain regions processing the incoming information are adapted to the reception of fundamentally different sensory cues has not been investigated in hemimetabolous insects. Here we describe the antennal sensilla, the general brain structure, and the antennal sensory pathways in the last six nymphal instars of Libellula depressa, in comparison with earlier published data from adults, using scanning electron microscopy, and antennal receptor neuron and antennal lobe output neuron mass-tracing with tetramethylrhodamin. Brain structure was visualized with an anti-synapsin antibody. Differently from adults, the nymphal antennal flagellum harbors many mechanoreceptive sensilla, one olfactory, and two thermo-hygroreceptive sensilla at all investigated instars. The nymphal brain is very similar to the adult brain throughout development, despite the considerable differences in antennal sensilla and habitat. Like in adults, nymphal brains contain mushroom bodies lacking calyces and small aglomerular antennal lobes. Antennal fibers innervate the antennal lobe similar to adult brains and the gnathal ganglion more prominently than in adults. Similar brain structures are thus used in L. depressa nymphs and adults to process diverging sensory information.

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