scholarly journals Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction

2019 ◽  
Vol 216 (4) ◽  
pp. 900-915 ◽  
Author(s):  
Thomas D. Arnold ◽  
Carlos O. Lizama ◽  
Kelly M. Cautivo ◽  
Nicolas Santander ◽  
Lucia Lin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Tgfβ Signaling ◽  
Critical Determinant ◽  
Conditional Deletion ◽  
Stepwise Development ◽  
The Central Nervous System

Microglia play a pivotal role in the coordination of brain development and have emerged as a critical determinant in the progression of neurodegenerative diseases; however, the role of microglia in the onset and progression of neurodevelopmental disorders is less clear. Here we show that conditional deletion of αVβ8 from the central nervous system (Itgb8ΔCNS mice) blocks microglia in their normal stepwise development from immature precursors to mature microglia. These “dysmature” microglia appear to result from reduced TGFβ signaling during a critical perinatal window, are distinct from microglia with induced reduction in TGFβ signaling during adulthood, and directly cause a unique neurodevelopmental syndrome characterized by oligodendrocyte maturational arrest, interneuron loss, and spastic neuromotor dysfunction. Consistent with this, early (but not late) microglia depletion completely reverses this phenotype. Together, these data identify novel roles for αVβ8 and TGFβ signaling in coordinating microgliogenesis with brain development and implicate abnormally programmed microglia or their products in human neurodevelopmental disorders that share this neuropathology.

Expression Analyses of Mediator Complex Subunit 13-Like: A Responsible Gene for Neurodevelopmental Disorders during Mouse Brain Development

2021 ◽  
pp. 1-10
Author(s):  
Nanako Hamada ◽  
Ikuko Iwamoto ◽  
Masashi Nishikawa ◽  
Koh-ichi Nagata
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Brain Development ◽  
Developmental Stage ◽  
Expression Profile ◽  
Neurodevelopmental Disorders ◽  
Mediator Complex ◽  
Cortical Plate ◽  
The Central Nervous System

MED13L (mediator complex subunit 13-like) is a component of the mediator complex, which functions as a regulator for gene transcription. Since gene abnormalities in MED13L are responsible for neurodevelopmental disorders, MED13L is presumed to play an essential role in brain development. In this study, we prepared a specific antibody against MED13L, anti-MED13L, and analyzed its expression profile in mouse tissues with focusing on the central nervous system. In Western blotting, MED13L exhibited a tissue-dependent expression profile in the adult mouse and was expressed in a developmental stage-dependent manner in brain. In immunofluorescence analyses, MED13L was at least partially colocalized with pre- and post-synaptic markers, synaptophysin, and PSD95, in primary cultured hippocampal neurons. Immunohistochemical analyses revealed that MED13L was relatively highly expressed in ventricular zone surface of cerebral cortex, and was also located both in the cytoplasm and nucleus of neurons in the cortical plate at embryonic day 14. Then, MED13L showed diffuse cytoplasmic distribution throughout the cerebral cortex at the postnatal day (P) 30. In addition, MED13L appeared to be localized in cell type- and developmental stage-specific manners in the hippocampus and cerebellum. These results suggest that MED13L is involved in the development of the central nervous system and synaptic function.

scholarly journals Microglia-mediated synaptic elimination in neuronal development and disease

2018 ◽  
Vol 119 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Brendan S. Whitelaw
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Immune Cells ◽  
Neurodevelopmental Disorders ◽  
Neuronal Development ◽  
Neuronal Connectivity ◽  
Wide Range ◽  
The Central Nervous System

It has recently become clear that microglia, the immune cells of the central nervous system, are far more active in the healthy brain than previously thought. Microglia facilitate many stages of brain development by shaping neuronal connectivity via synaptic elimination. Dysfunction of these same processes likely underlies a wide range of neurological and neurodevelopmental disorders.

Role of a nurse in the rehabilitation of children using ReviMotion hardware and software complex

2020 ◽  
pp. 49-56
Author(s):  
T. Shirshova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
School Age Children ◽  
Equipment Management ◽  
School Age ◽  
Rehabilitation Process ◽  
Software Complex ◽  
Trained Personnel ◽  
The Central Nervous System

Disorders of the musculoskeletal system in school-age children occupy 1-2 places in the structure of functional abnormalities. Cognitive impairment without organic damage to the central nervous system is detected in 30-56% of healthy school children. Along with the increase in the incidence rate, the demand for rehabilitation systems, which allow patients to return to normal life as soon as possible and maintain the motivation for the rehabilitation process, is also growing. Adaptation of rehabilitation techniques, ease of equipment management, availability of specially trained personnel and availability of technical support for complexes becomes important.

The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

2019 ◽  
Vol 20 (7) ◽  
pp. 750-758 ◽  
Author(s):  
Yi Wu ◽  
Hengxun He ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropeptide Y ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
Vital Role ◽  
Gut Peptides ◽  
Nonalcoholic Fatty Liver ◽  
The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

The Yin and Yang of BK Channels in Epilepsy

2018 ◽  
Vol 17 (4) ◽  
pp. 272-279 ◽  
Author(s):  
Yudan Zhu ◽  
Shuzhang Zhang ◽  
Yijun Feng ◽  
Qian Xiao ◽  
Jiwei Cheng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Bk Channels ◽  
Bk Channel ◽  
Potential Shape ◽  
Yin And Yang ◽  
The Central Nervous System ◽  
Action Potential Shape ◽  
Excitability Of Neurons

Background & Objective: The large conductance calcium-activated potassium (BK) channel, extensively distributed in the central nervous system (CNS), is considered as a vital player in the pathogenesis of epilepsy, with evidence implicating derangement of K+ as well as regulating action potential shape and duration. However, unlike other channels implicated in epilepsy whose function in neurons could clearly be labeled “excitatory” or “inhibitory”, the unique physiological behavior of the BK channel allows it to both augment and decrease the excitability of neurons. Thus, the role of BK in epilepsy is controversial so far, and a growing area of intense investigation. Conclusion: Here, this review aims to highlight recent discoveries on the dichotomous role of BK channels in epilepsy, focusing on relevant BK-dependent pro- as well as antiepileptic pathways, and discuss the potential of BK specific modulators for the treatment of epilepsy.

Bone-brain crosstalk and potential associated diseases

2016 ◽  
Vol 28 (2) ◽  
Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cognitive Functions ◽  
Intimate Relationship ◽  
Whole Body ◽  
Reciprocal Relationships ◽  
Skeletal Homeostasis ◽  
The Central Nervous System ◽  
The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

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