scholarly journals Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
N Sumru Bayin ◽  
Alexandre Wojcinski ◽  
Aurelien Mourton ◽  
Hiromitsu Saito ◽  
Noboru Suzuki ◽  
...  
Keyword(s):  
Purkinje Neurons ◽  
New Paradigm ◽  
Perinatal Brain Injury ◽  
Cerebellar Function ◽  
Efficient Regeneration ◽  
Age Dependent ◽  
Cerebellum Development ◽  
And Function ◽  
The Brain ◽  
Normal Cerebellum

Outside of the neurogenic niches of the brain, postmitotic neurons have not been found to undergo efficient regeneration. We demonstrate that mouse Purkinje cells (PCs), which are born at midgestation and are crucial for development and function of cerebellar circuits, are rapidly and fully regenerated following their ablation at birth. New PCs are produced from immature FOXP2+ Purkinje cell precursors (iPCs) that are able to enter the cell cycle and support normal cerebellum development. The number of iPCs and their regenerative capacity, however, diminish soon after birth and consequently PCs are poorly replenished when ablated at postnatal day five. Nevertheless, the PC-depleted cerebella reach a normal size by increasing cell size, but scaling of neuron types is disrupted and cerebellar function is impaired. Our findings provide a new paradigm in the field of neuron regeneration by identifying a population of immature neurons that buffers against perinatal brain injury in a stage-dependent process.

scholarly journals Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons

2018 ◽  
Author(s):  
N. Sumru Bayin ◽  
Alexandre Wojcinski ◽  
Aurelien Mourton ◽  
Hiromitsu Saito ◽  
Noboru Suzuki ◽  
...  
Keyword(s):  
Dependent Manner ◽  
New Paradigm ◽  
Perinatal Brain Injury ◽  
Cerebellar Function ◽  
Efficient Regeneration ◽  
Age Dependent ◽  
Cerebellum Development ◽  
And Function ◽  
The Brain ◽  
Normal Cerebellum

AbstractOutside of the neurogenic niches of the brain, postmitotic neurons have not been found to undergo efficient regeneration. Here we demonstrate that Purkinje cells (PCs), which are born at midgestation and are crucial for both development and function of cerebellar circuits, are rapidly and fully regenerated following their ablation at birth. New PCs are produced by a previously unidentified progenitor population and support normal cerebellum development. The number of PC progenitors and their regenerative capacity, however, diminish soon after birth, and consequently PCs are poorly replenished when ablated at postnatal day 5. Nevertheless, the PC-depleted cerebella reach a normal size by increasing cell size, but scaling of neuron types is disrupted and cerebellar function is impaired. Our findings thus provide a new paradigm in the field of neuron regeneration by identifying a unipotent neural progenitor that buffers against perinatal brain injury in a stage-dependent process.One sentence summaryInjury induces a dormant progenitor population present at birth to regenerate cerebellar neurons in a time-dependent manner.

Ultrastructure of developing visual cortical synapses in the cat superior colliculus

1991 ◽  
Vol 49 ◽  
pp. 156-157
Author(s):  
Caroline A. Miller ◽  
Laura L. Bruce
Keyword(s):  
Superior Colliculus ◽  
Phosphate Buffer ◽  
Receptive Fields ◽  
Visual Cortical Area ◽  
Cortical Synapses ◽  
Visual Cortical ◽  
And Function ◽  
Phosphate Buffered Saline ◽  
The Brain ◽  
Cat Superior Colliculus

The first visual cortical axons arrive in the cat superior colliculus by the time of birth. Adultlike receptive fields develop slowly over several weeks following birth. The developing cortical axons go through a sequence of changes before acquiring their adultlike morphology and function. To determine how these axons interact with neurons in the colliculus, cortico-collicular axons were labeled with biocytin (an anterograde neuronal tracer) and studied with electron microscopy.Deeply anesthetized animals received 200-500 nl injections of biocytin (Sigma; 5% in phosphate buffer) in the lateral suprasylvian visual cortical area. After a 24 hr survival time, the animals were deeply anesthetized and perfused with 0.9% phosphate buffered saline followed by fixation with a solution of 1.25% glutaraldehyde and 1.0% paraformaldehyde in 0.1M phosphate buffer. The brain was sectioned transversely on a vibratome at 50 μm. The tissue was processed immediately to visualize the biocytin.

Ausnahmesegment

2018 ◽  
Vol 48 (191) ◽  
Author(s):  
Barbara Schönig
Keyword(s):  
Welfare State ◽  
Social Housing ◽  
Integrated Approach ◽  
New Paradigm ◽  
Development Models ◽  
Form And Function ◽  
Institutional Organization ◽  
National Welfare ◽  
And Function ◽  
The Welfare State

Going along with the end of the “golden age” of the welfare state, the fordist paradigm of social housing has been considerably transformed. From the 1980s onwards, a new paradigm of social housing has been shaped in Germany in terms of provision, institutional organization and design. This transformation can be interpreted as a result of the interplay between the transformation of national welfare state and housing policies, the implementation of entrepreneurial urban policies and a shift in architectural and urban development models. Using an integrated approach to understand form and function of social housing, the paper characterizes the new paradigm established and nevertheless interprets it within the continuity of the specific German welfare resp. housing regime, the “German social housing market economy”.

Revision Targeted Muscle Reinnervation Improves Secondary Pain Insult in an Upper Extremity Amputee: A Case Report

Hand ◽  
2021 ◽  
pp. 155894472199246
Author(s):  
David D. Rivedal ◽  
Meng Guo ◽  
James Sanger ◽  
Aaron Morgan
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerves ◽  
Nerve Biopsy ◽  
Sensory Cortex ◽  
Denervated Muscle ◽  
Unique Case ◽  
Targeted Muscle Reinnervation ◽  
Muscle Reinnervation ◽  
And Function ◽  
The Brain

Targeted muscle reinnervation (TMR) has been shown to improve phantom and neuropathic pain in both the acute and chronic amputee population. Through rerouting of major peripheral nerves into a newly denervated muscle, TMR harnesses the plasticity of the brain, helping to revert the sensory cortex back toward the preinsult state, effectively reducing pain. We highlight a unique case of an above-elbow amputee for sarcoma who was initially treated with successful transhumeral TMR. Following inadvertent nerve biopsy of a TMR coaptation site, his pain returned, and he was unable to don his prosthetic. Revision of his TMR to a more proximal level was performed, providing improved pain and function of the amputated arm. This is the first report to highlight the concept of secondary neuroplasticity and successful proximal TMR revision in the setting of multiple insults to the same extremity.

scholarly journals The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

2020 ◽  
Author(s):  
Enrico Castroflorio ◽  
Joery den Hoed ◽  
Daria Svistunova ◽  
Mattéa J. Finelli ◽  
Alberto Cebrian-Serrano ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Regulatory Protein ◽  
Molecular Function ◽  
Neuronal Connectivity ◽  
Nuclear Receptor Coactivator ◽  
Lysm Domain ◽  
Behavioural Assessment ◽  
And Function ◽  
The Brain

Abstract Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disorders, although their exact roles in disease remain unclear. For example, nuclear receptor coactivator 7 (NCOA7) has been associated with autism, although almost nothing is known regarding the mode-of-action of this TLDc protein in the nervous system. Here we investigated the molecular function of NCOA7 in neurons and generated a novel mouse model to determine the consequences of deleting this locus in vivo. We show that NCOA7 interacts with the cytoplasmic domain of the vacuolar (V)-ATPase in the brain and demonstrate that this protein is required for normal assembly and activity of this critical proton pump. Neurons lacking Ncoa7 exhibit altered development alongside defective lysosomal formation and function; accordingly, Ncoa7 deletion animals exhibited abnormal neuronal patterning defects and a reduced expression of lysosomal markers. Furthermore, behavioural assessment revealed anxiety and social defects in mice lacking Ncoa7. In summary, we demonstrate that NCOA7 is an important V-ATPase regulatory protein in the brain, modulating lysosomal function, neuronal connectivity and behaviour; thus our study reveals a molecular mechanism controlling endolysosomal homeostasis that is essential for neurodevelopment. Graphic abstract

scholarly journals Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Katherine M Ranard ◽  
Matthew J Kuchan ◽  
John W Erdman
Keyword(s):  
Animal Model ◽  
Vitamin E ◽  
Mouse Model ◽  
Wild Type ◽  
Future Studies ◽  
Neurological Outcomes ◽  
Transfer Protein ◽  
And Function ◽  
The Brain ◽  
Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

scholarly journals Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 957
Author(s):  
Brad T. Casali ◽  
Erin G. Reed-Geaghan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cells ◽  
Expression Patterns ◽  
Brain Parenchyma ◽  
Primary Role ◽  
And Function ◽  
Inflammatory Milieu ◽  
The Brain ◽  
Homeostatic State

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.

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