scholarly journals What Do Microglia Really Do in Healthy Adult Brain?

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1293 ◽  
Author(s):  
Marcus Augusto-Oliveira ◽  
Gabriela P. Arrifano ◽  
Amanda Lopes-Araújo ◽  
Leticia Santos-Sacramento ◽  
Priscila Y. Takeda ◽  
...  
Keyword(s):  
Healthy Adult ◽  
Cellular Level ◽  
Adult Brain ◽  
Neuronal Function ◽  
Learning Deficits ◽  
Neuroinflammatory Response ◽  
Circulating Cells ◽  
Cognition And Learning ◽  
And Behavior ◽  
Brain Homeostasis

Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. However, less is known about their role in the healthy adult brain. Astrocytes and oligodendrocytes are widely accepted to strongly contribute to the maintenance of brain homeostasis and to modulate neuronal function. On the other hand, contribution of microglia to cognition and behavior is only beginning to be understood. The ability to probe their function has become possible using microglial depletion assays and conditional mutants. Studies have shown that the absence of microglia results in cognitive and learning deficits in rodents during development, but this effect is less pronounced in adults. However, evidence suggests that microglia play a role in cognition and learning in adulthood and, at a cellular level, may modulate adult neurogenesis. This review presents the case for repositioning microglia as key contributors to the maintenance of homeostasis and cognitive processes in the healthy adult brain, in addition to their classical role as sentinels coordinating the neuroinflammatory response to tissue damage and disease.

Information Processing in the Mammalian Olfactory System

2005 ◽  
Vol 85 (1) ◽  
pp. 281-317 ◽  
Author(s):  
Pierre-Marie Lledo ◽  
Gilles Gheusi ◽  
Jean-Didier Vincent
Keyword(s):  
Olfactory System ◽  
Cellular Level ◽  
Adult Brain ◽  
Organizational Strategies ◽  
Cellular Mechanisms ◽  
Brain Functions ◽  
Olfactory Systems ◽  
And Behavior ◽  
High Degree ◽  
The Brain

Recently, modern neuroscience has made considerable progress in understanding how the brain perceives, discriminates, and recognizes odorant molecules. This growing knowledge took over when the sense of smell was no longer considered only as a matter for poetry or the perfume industry. Over the last decades, chemical senses captured the attention of scientists who started to investigate the different stages of olfactory pathways. Distinct fields such as genetic, biochemistry, cellular biology, neurophysiology, and behavior have contributed to provide a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. So far, the combination of these approaches has been most effective at the cellular level, but there are already signs, and even greater hope, that the same is gradually happening at the systems level. This review summarizes the current ideas concerning the cellular mechanisms and organizational strategies used by the olfactory system to process olfactory information. We present findings that exemplified the high degree of olfactory plasticity, with special emphasis on the first central relay of the olfactory system. Recent observations supporting the necessity of such plasticity for adult brain functions are also discussed. Due to space constraints, this review focuses mainly on the olfactory systems of vertebrates, and primarily those of mammals.

WNT-Frizzled signalling and the many paths to neural development and adult brain homeostasis

10.2741/2077 ◽  
2007 ◽  
Vol 12 (1) ◽  
pp. 492 ◽  
Author(s):  
Jordane Malaterre
Keyword(s):  
Neural Development ◽  
Adult Brain ◽  
The Many ◽  
Brain Homeostasis

scholarly journals The maintenance of specific aspects of neuronal function and behavior is dependent on programmed cell death of adult-generated neurons in the dentate gyrus

2009 ◽  
Vol 29 (7) ◽  
pp. 1408-1421 ◽  
Author(s):  
Woon Ryoung Kim ◽  
Ok-hee Park ◽  
Sukwoo Choi ◽  
Se-Young Choi ◽  
Soon Kwon Park ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dentate Gyrus ◽  
Neuronal Function ◽  
And Behavior

scholarly journals Diurnal Microstructural Variations in Healthy Adult Brain Revealed by Diffusion Tensor Imaging

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e84822 ◽  
Author(s):  
Chunxiang Jiang ◽  
Lijuan Zhang ◽  
Chao Zou ◽  
Xiaojing Long ◽  
Xin Liu ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Healthy Adult ◽  
Diffusion Tensor ◽  
Adult Brain

scholarly journals Behavioral and Neuroanatomical Consequences of Cell-Type Specific Loss of Dopamine D2 Receptors in the Mouse Cerebral Cortex

2022 ◽  
Vol 15 ◽  
Author(s):  
Gloria S. Lee ◽  
Devon L. Graham ◽  
Brenda L. Noble ◽  
Taylor S. Trammell ◽  
Deirdre M. McCarthy ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Motor Coordination ◽  
Cellular Level ◽  
D2 Receptors ◽  
Dopamine D2 Receptors ◽  
Inhibitory Neurons ◽  
Specific Loss ◽  
Dopamine D2 ◽  
And Behavior ◽  
Circuit Formation

Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.

scholarly journals A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics

2021 ◽  
Author(s):  
Joseph Burclaff ◽  
R. Jarrett Bliton ◽  
Keith A Breau ◽  
Meryem T Ok ◽  
Ismael Gomez-Martinez ◽  
...  
Keyword(s):  
Small Intestine ◽  
Single Cell ◽  
Drug Targets ◽  
Healthy Adult ◽  
Cellular Level ◽  
Cell Junction ◽  
Marker Genes ◽  
Human Small Intestine ◽  
Adult Human ◽  
Human Intestinal Epithelium

Background and Aims: Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies in healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics from 3 humans covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon. Methods: 12,590 single epithelial cells from three independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and capacity for response to extrinsic signals along the gut axis across different humans. Results: Cells were assigned to 25 epithelial lineage clusters. Human intestinal stem cells (ISCs) are not specifically marked by many murine ISC markers. Lysozyme expression is not unique to Paneth cells (PCs), and PCs lack expression of expected niche-factors. BEST4 cells express NPY and show functional and maturational differences between SI and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell-junction, and nutrient absorption genes show unappreciated regional expression differences across lineages. Differential expression of receptors and drug targets across lineages reveals biological variation and potential for variegated responses. Conclusions: Our study identifies novel lineage marker genes; covers regional differences; shows important differences between mouse and human gut epithelium; and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves data gaps in anatomical regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.

scholarly journals Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hui Ye ◽  
Shamsideen A Ojelade ◽  
David Li-Kroeger ◽  
Zhongyuan Zuo ◽  
Liping Wang ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Protein Complex ◽  
Adult Brain ◽  
Aging Brain ◽  
Gtpase Activating Protein ◽  
Ultrastructural Evidence ◽  
Aging Adults ◽  
And Function ◽  
Brain Homeostasis

Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. Although implicated in both Parkinson’s and Alzheimer’s disease, our understanding of retromer function in the adult brain remains limited, in part because Vps35 and Vps26 are essential for development. In Drosophila, we find that Vps29 is dispensable for embryogenesis but required for retromer function in aging adults, including for synaptic transmission, survival, and locomotion. Unexpectedly, in Vps29 mutants, Vps35 and Vps26 proteins are normally expressed and associated, but retromer is mislocalized from neuropil to soma with the Rab7 GTPase. Further, Vps29 phenotypes are suppressed by reducing Rab7 or overexpressing the GTPase activating protein, TBC1D5. With aging, retromer insufficiency triggers progressive endolysosomal dysfunction, with ultrastructural evidence of impaired substrate clearance and lysosomal stress. Our results reveal the role of Vps29 in retromer localization and function, highlighting requirements for brain homeostasis in aging.

scholarly journals Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Emily A Bayer ◽  
Rebecca C Stecky ◽  
Lauren Neal ◽  
Phinikoula S Katsamba ◽  
Goran Ahlsen ◽  
...  
Keyword(s):  
Specific Protein ◽  
Protein Stabilization ◽  
Protein Domain ◽  
Synaptic Connectivity ◽  
Sexually Dimorphic ◽  
Posttranslational Regulation ◽  
Neuronal Function ◽  
Related Transcription Factor ◽  
Sex Specificity ◽  
And Behavior

Sex-specific synaptic connectivity is beginning to emerge as a remarkable, but little explored feature of animal brains. We describe here a novel mechanism that promotes sexually dimorphic neuronal function and synaptic connectivity in the nervous system of the nematode Caenorhabditis elegans. We demonstrate that a phylogenetically conserved, but previously uncharacterized Doublesex/Mab-3 related transcription factor (DMRT), dmd-4, is expressed in two classes of sex-shared phasmid neurons specifically in hermaphrodites but not in males. We find dmd-4 to promote hermaphrodite-specific synaptic connectivity and neuronal function of phasmid sensory neurons. Sex-specificity of DMD-4 function is conferred by a novel mode of posttranslational regulation that involves sex-specific protein stabilization through ubiquitin binding to a phylogenetically conserved but previously unstudied protein domain, the DMA domain. A human DMRT homolog of DMD-4 is controlled in a similar manner, indicating that our findings may have implications for the control of sexual differentiation in other animals as well.

RETHINKING INNATENESS: A CONNECTIONIST PERSPECTIVE ON DEVELOPMENT.Jeffrey L. Elman, Elizabeth A. Bates, Mark H. Johnson, Annette Karmiloff-Smith, Domenico Parisi, & Kim Plunkett. Cambridge, MA: MIT Press, 1996. Pp. xviii + 447. $45.00 cloth.

1998 ◽  
Vol 20 (3) ◽  
pp. 451-451
Author(s):  
Nick Ellis
Keyword(s):  
Cognitive Psychology ◽  
Dynamical Systems ◽  
Cellular Level ◽  
Regulatory Control ◽  
Synaptic Connectivity ◽  
Special Focus ◽  
Human Cortex ◽  
Domain Specific ◽  
Molecular Arrangement ◽  
And Behavior

In this provocative book, six coauthors, representing cognitive psychology, connectionism, neurobiology, and dynamical-systems theory, synthesize a new theoretical framework for cognitive development with special focus on language acquisition. In the Emergentist perspective, interactions occurring at all levels, from genes to environment, give rise to emergent forms and behavior. These outcomes may be highly constrained and universal, but they are not themselves directly contained in the genes in any domain-specific way. The human body contains perhaps 5 × 1028 bits of information in its molecular arrangement, but our genome contains only about 105 bits of information. Thus, we are over 20 orders of magnitude short of being mosaic organisms, where development is prespecified in the genes. Our development is under regulatory control, where precise pathways to adulthood reflect numerous interactions at the cellular level occurring throughout development. The human cortex is plastic, its architecture reflects experience; innate specification of synaptic connectivity in the cortex is highly unlikely. Theories of language must reflect this—they must be biologically, developmentally, and ecologically plausible. Linguistic representational nativism is just not tenable. It is so implausible that UG could be directly encoded in the genotype that we must explore the alternatives. So the answer is not “Nature.” Nor, as the authors so clearly argue, is it “Nature or Nuture.” Rather, it is “Nature and Nurture.”

scholarly journals Brain Structural and Functional Alterations in Mice Prenatally Exposed to LPS Are Only Partially Rescued by Anti-Inflammatory Treatment

2020 ◽  
Vol 10 (9) ◽  
pp. 620 ◽  
Author(s):  
Francesca Aria ◽  
Sara A. Bonini ◽  
Valentina Cattaneo ◽  
Marika Premoli ◽  
Andrea Mastinu ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Preventive Treatment ◽  
Epidemiological Studies ◽  
Adult Brain ◽  
Biological Mechanisms ◽  
Behavioral Alterations ◽  
Maternal Immune System ◽  
Behavioral Impairments ◽  
And Behavior ◽  
First Time

Aberrant immune activity during neurodevelopment could participate in the generation of neurological dysfunctions characteristic of several neurodevelopmental disorders (NDDs). Numerous epidemiological studies have shown a link between maternal infections and NDDs risk; animal models of maternal immune activation (MIA) have confirmed this association. Activation of maternal immune system during pregnancy induces behavioral and functional alterations in offspring but the biological mechanisms at the basis of these effects are still poorly understood. In this study, we investigated the effects of prenatal lipopolysaccharide (LPS) exposure in peripheral and central inflammation, cortical cytoarchitecture and behavior of offspring (LPS-mice). LPS-mice reported a significant increase in interleukin-1β (IL-1β) serum level, glial fibrillary acidic protein (GFAP)- and ionized calcium-binding adapter molecule 1 (Iba1)-positive cells in the cortex. Furthermore, cytoarchitecture analysis in specific brain areas, showed aberrant alterations in minicolumns’ organization in LPS-mice adult brain. In addition, we demonstrated that LPS-mice presented behavioral alterations throughout life. In order to better understand biological mechanisms whereby LPS induced these alterations, dams were treated with meloxicam. We demonstrated for the first time that exposure to LPS throughout pregnancy induces structural permanent alterations in offspring brain. LPS-mice also present severe behavioral impairments. Preventive treatment with meloxicam reduced inflammation in offspring but did not rescue them from structural and behavioral alterations.

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