scholarly journals In Search of Molecular Markers for Cerebellar Neurons

2021 ◽  
Vol 22 (4) ◽  
pp. 1850
Author(s):  
Wing Yip Tam ◽  
Xia Wang ◽  
Andy S. K. Cheng ◽  
Kwok-Kuen Cheung
Keyword(s):  
Cognitive Deficits ◽  
Motor Coordination ◽  
Normal Development ◽  
Genetic Manipulation ◽  
Cell Types ◽  
Functional Study ◽  
Cerebellar Neurons ◽  
The Brain ◽  
Neuronal Type

The cerebellum, the region of the brain primarily responsible for motor coordination and balance, also contributes to non-motor functions, such as cognition, speech, and language comprehension. Maldevelopment and dysfunction of the cerebellum lead to cerebellar ataxia and may even be associated with autism, depression, and cognitive deficits. Hence, normal development of the cerebellum and its neuronal circuitry is critical for the cerebellum to function properly. Although nine major types of cerebellar neurons have been identified in the cerebellar cortex to date, the exact functions of each type are not fully understood due to a lack of cell-specific markers in neurons that renders cell-specific labeling and functional study by genetic manipulation unfeasible. The availability of cell-specific markers is thus vital for understanding the role of each neuronal type in the cerebellum and for elucidating the interactions between cell types within both the developing and mature cerebellum. This review discusses various technical approaches and recent progress in the search for cell-specific markers for cerebellar neurons.

scholarly journals The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi
Keyword(s):  
Alzheimer Disease ◽  
Glial Cells ◽  
Cell Types ◽  
The Past ◽  
The Central Nervous System ◽  
Diseased State ◽  
The Brain ◽  
Alzheimer Disease Pathogenesis ◽  
Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

2019 ◽  
Vol 128 (06/07) ◽  
pp. 388-394
Author(s):  
Helge Müller-Fielitz ◽  
Markus Schwaninger
Keyword(s):  
Energy Homeostasis ◽  
Genetic Manipulation ◽  
Heart Function ◽  
Feedback Regulation ◽  
Target Organs ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Hpt Axis ◽  
The Brain

AbstractThyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

scholarly journals Non-apoptotic enteroblast-specific role of the initiator caspase Dronc for development and homeostasis of the Drosophila intestine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jillian L. Lindblad ◽  
Meghana Tare ◽  
Alla Amcheslavsky ◽  
Alicia Shields ◽  
Andreas Bergmann
Keyword(s):  
Normal Development ◽  
Cell Lineage ◽  
Cell Types ◽  
Specific Role ◽  
Mutant Phenotype ◽  
Apoptotic Pathway ◽  
Specific Expression ◽  
Card Domain

AbstractThe initiator caspase Dronc is the only CARD-domain containing caspase in Drosophila and is essential for apoptosis. Here, we report that homozygous dronc mutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression of dronc+ in dronc mutant animals, suggesting that proper Dronc function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown of dronc in adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Dronc do not require the apoptotic pathway and thus occur in a non-apoptotic manner. In summary, we demonstrate that an apoptotic initiator caspase has a very critical non-apoptotic function for normal development and for the control of the cell lineage in the adult midgut and therefore for proper physiology and homeostasis.

scholarly journals Identification of Novel Roles of the Cytochrome P450 System in Early Embryogenesis: Effects on Vasculogenesis and Retinoic Acid Homeostasis

2003 ◽  
Vol 23 (17) ◽  
pp. 6103-6116 ◽  
Author(s):  
Diana M. E. Otto ◽  
Colin J. Henderson ◽  
Dianne Carrie ◽  
Megan Davey ◽  
Thomas E. Gundersen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Cell Types ◽  
Monooxygenase System ◽  
Cytochrome P450 System ◽  
Expression Of Genes ◽  
Close Relationship ◽  
Metabolism Of Xenobiotics ◽  
The Brain

ABSTRACT The cytochrome P450-dependent monooxygenase system catalyzes the metabolism of xenobiotics and endogenous compounds, including hormones and retinoic acid. In order to establish the role of these enzymes in embryogenesis, we have inactivated the system through the deletion of the gene for the electron donor to all microsomal P450 proteins, cytochrome P450 reductase (Cpr). Mouse embryos homozygous for this deletion died in early to middle gestation (∼9.5 days postcoitum [dpc]) and exhibited a number of novel phenotypes, including the severe inhibition of vasculogenesis and hematopoiesis. In addition, defects in the brain, limbs, and cell types where CPR was shown to be expressed were observed. Some of the observed abnormalities have been associated with perturbations in retinoic acid homeostasis in later embryogenesis. Consistent with this possibility, embryos at 9.5 dpc had significantly elevated levels of retinoic acid and reduced levels of retinol. Further, some of the observed phenotypes could be either reversed or exacerbated by decreasing or increasing maternal retinoic acid exposure, respectively. Detailed analysis demonstrated a close relationship between the observed phenotype and the expression of genes controlling vasculogenesis. These data demonstrate that the cytochrome P450 system plays a key role in early embryonic development; this process appears to be, at least in part, controlled by regional concentrations of retinoic acid and has profound effects on blood vessel formation.

scholarly journals Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

2020 ◽  
Author(s):  
Pengbo Shi ◽  
Zhaosu Li ◽  
Xing Xu ◽  
Jiaxun Nie ◽  
Dekang Liu ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Cognitive Deficits ◽  
Glutamate Uptake ◽  
Cognitive Disorders ◽  
Memory Deficits ◽  
Therapeutic Interventions ◽  
Therapeutic Effects ◽  
Non Invasive ◽  
The Brain

ABSTRACTMethamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a key target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.

scholarly journals Drosophila mef2 is essential for normal mushroom body and wing development

2018 ◽  
Author(s):  
Jill R. Crittenden ◽  
Efthimios M. C. Skoulakis ◽  
Elliott. S. Goldstein ◽  
Ronald L. Davis
Keyword(s):  
Nuclear Localization ◽  
Mushroom Body ◽  
Normal Development ◽  
Cell Types ◽  
Mushroom Bodies ◽  
Wing Development ◽  
Myocyte Enhancer Factor 2 ◽  
Multiple Cell ◽  
The Brain ◽  
Enhancer Factor

ABSTRACTMEF2 (myocyte enhancer factor 2) transcription factors are found in the brain and muscle of insects and vertebrates and are essential for the differentiation of multiple cell types. We show that in the fruitfly Drosophila, MEF2 is essential for normal development of wing veins, and for mushroom body formation in the brain. In embryos mutant for D-mef2, there was a striking reduction in the number of mushroom body neurons and their axon bundles were not detectable. D-MEF2 expression coincided with the formation of embryonic mushroom bodies and, in larvae, expression onset was confirmed to be in post-mitotic neurons. With a D-mef2 point mutation that disrupts nuclear localization, we find that D-MEF2 is restricted to a subset of Kenyon cells that project to the α/β, and γ axonal lobes of the mushroom bodies, but not to those forming the α’/β’ lobes. Our findings that ancestral mef2 is specifically important in dopamine-receptive neurons has broad implications for its function in mammalian neurocircuits.

scholarly journals The Neurobiology of Selenium: Looking Back and to the Future

2021 ◽  
Vol 15 ◽  
Author(s):  
Ulrich Schweizer ◽  
Simon Bohleber ◽  
Wenchao Zhao ◽  
Noelia Fradejas-Villar
Keyword(s):  
Cell Biology ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Epileptic Seizures ◽  
Cell Types ◽  
Mammalian Brain ◽  
The Individual ◽  
The Brain ◽  
Looking Back

Eighteen years ago, unexpected epileptic seizures in Selenop-knockout mice pointed to a potentially novel, possibly underestimated, and previously difficult to study role of selenium (Se) in the mammalian brain. This mouse model was the key to open the field of molecular mechanisms, i.e., to delineate the roles of selenium and individual selenoproteins in the brain, and answer specific questions like: how does Se enter the brain; which processes and which cell types are dependent on selenoproteins; and, what are the individual roles of selenoproteins in the brain? Many of these questions have been answered and much progress is being made to fill remaining gaps. Mouse and human genetics have together boosted the field tremendously, in addition to traditional biochemistry and cell biology. As always, new questions have become apparent or more pressing with solving older questions. We will briefly summarize what we know about selenoproteins in the human brain, glance over to the mouse as a useful model, and then discuss new questions and directions the field might take in the next 18 years.

scholarly journals S100A6 and Its Brain Ligands in Neurodegenerative Disorders

2020 ◽  
Vol 21 (11) ◽  
pp. 3979
Author(s):  
Anna Filipek ◽  
Wiesława Leśniak
Keyword(s):  
Mammalian Cells ◽  
Brain Structures ◽  
Cell Types ◽  
Cytoskeletal Organization ◽  
High Level ◽  
S100a6 Protein ◽  
Different Cell Types ◽  
The Brain ◽  
Lateral Sclerosis

The S100A6 protein is present in different mammalian cells and tissues including the brain. It binds Ca2+ and Zn2+ and interacts with many target proteins/ligands. The best characterized ligands of S100A6, expressed at high level in the brain, include CacyBP/SIP and Sgt1. Research concerning the functional role of S100A6 and these two ligands indicates that they are involved in various signaling pathways that regulate cell proliferation, differentiation, cytoskeletal organization, and others. In this review, we focused on the expression/localization of these proteins in the brain and on their possible role in neurodegenerative diseases. Published results demonstrate that S100A6, CacyBP/SIP, and Sgt1 are expressed in various brain structures and in the spinal cord and can be found in different cell types including neurons and astrocytes. When it comes to their possible involvement in nervous system pathology, it is evident that their expression/level and/or subcellular localization is changed when compared to normal conditions. Among diseases in which such changes have been observed are Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), epileptogenesis, Parkinson’s disease (PD), Huntington’s disease (HD), and others.

Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney

2000 ◽  
Vol 278 (5) ◽  
pp. F737-F746 ◽  
Author(s):  
Vanishree Murthy ◽  
Luciana A. Haddad ◽  
Nicole Smith ◽  
Denise Pinney ◽  
Robert Tyszkowski ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Cell Types ◽  
Intercalated Cells ◽  
Autosomal Dominant Disorder ◽  
Specific Expression ◽  
Multiple Organs ◽  
Distal Tubules ◽  
Kidney Lesions ◽  
The Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs, notably the brain and kidneys. The disease is caused by mutations in TSC1or TSC2 genes, coding hamartin and tuberin, respectively. Immunofluorescence analysis of tuberin and hamartin performed here demonstrates that both proteins are specifically expressed in the distal urinary tubule, comprising the distal tubules, connecting segment, and collecting ducts. Hamartin, distinct from tuberin, is expressed in the thick ascending limbs of Henle and in juxtaglomerular cells, where it colocalizes with renin. In positive epithelial cells, tuberin localizes to the cytoplasm as well as the apical membrane. Hamartin, however, preferentially localizes to the apical membrane. The two proteins colocalize at the apical membrane of type A intercalated cells and connecting tubule cells, whereas in type B intercalated cells they reveal a variable pattern of expression. The cell-specific expression of tuberin and hamartin described here will provide critical insight into the cell types that give rise to kidney lesions, and the tumor suppressor role of these proteins in TSC.

scholarly journals Regulation of the fructose transporter GLUT5 in health and disease

2008 ◽  
Vol 295 (2) ◽  
pp. E227-E237 ◽  
Author(s):  
Veronique Douard ◽  
Ronaldo P. Ferraris
Keyword(s):  
Normal Development ◽  
Cell Types ◽  
Mammary Glands ◽  
Fat Tissue ◽  
Metabolic Disturbances ◽  
Research Areas ◽  
Yield Information ◽  
Uptake Rates ◽  
Health And Disease

Fructose is now such an important component of human diets that increasing attention is being focused on the fructose transporter GLUT5. In this review, we describe the regulation of GLUT5 not only in the intestine and testis, where it was first discovered, but also in the kidney, skeletal muscle, fat tissue, and brain where increasing numbers of cell types have been found to have GLUT5. GLUT5 expression levels and fructose uptake rates are also significantly affected by diabetes, hypertension, obesity, and inflammation and seem to be induced during carcinogenesis, particularly in the mammary glands. We end by highlighting research areas that should yield information needed to better understand the role of GLUT5 during normal development, metabolic disturbances, and cancer.

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