scholarly journals The Role of FRMD7 in Idiopathic Infantile Nystagmus

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Rachel J. Watkins ◽  
Mervyn G. Thomas ◽  
Chris J. Talbot ◽  
Irene Gottlob ◽  
Sue Shackleton
Keyword(s):  
Actin Cytoskeleton ◽  
Neuronal Development ◽  
Ocular Motor ◽  
Primary Defect ◽  
Ferm Domain ◽  
Infantile Nystagmus ◽  
Membrane Extension ◽  
Ocular Motor Control ◽  
The Brain

Idiopathic infantile nystagmus (IIN) is an inherited disorder in which the nystagmus arises independently of any other symptoms, leading to the speculation that the disorder represents a primary defect in the area of the brain responsible for ocular motor control. The inheritance patterns are heterogeneous, however the most common form is X-linked.FRMD7resides at Xq26-27 and approximately 50% of X-linked IIN families map to this region. Currently 45 mutations withinFRMD7have been associated with IIN, confirming the importance ofFRMD7in the pathogenesis of the disease. Although mutations inFRMD7are known to cause IIN, very little is known about the function of the protein. FRMD7 contains a conserved N-terminal FERM domain suggesting that it may provide a link between the plasma membrane and actin cytoskeleton. Limited studies together with the knowledge of the function of other FERM domain containing proteins, suggest that FRMD7 may play a role in membrane extension during neuronal development through remodeling of the actin cytoskeleton.

scholarly journals MeCP2: The Genetic Driver of Rett Syndrome Epigenetics

2021 ◽  
Vol 12 ◽  
Author(s):  
Katrina V. Good ◽  
John B. Vincent ◽  
Juan Ausió
Keyword(s):  
Rett Syndrome ◽  
Neuronal Development ◽  
Neurodevelopmental Disorder ◽  
Epigenetic Mark ◽  
Initial Development ◽  
Genetic Ablation ◽  
Developmental Regression ◽  
The Stability ◽  
The Brain

Mutations in methyl CpG binding protein 2 (MeCP2) are the major cause of Rett syndrome (RTT), a rare neurodevelopmental disorder with a notable period of developmental regression following apparently normal initial development. Such MeCP2 alterations often result in changes to DNA binding and chromatin clustering ability, and in the stability of this protein. Among other functions, MeCP2 binds to methylated genomic DNA, which represents an important epigenetic mark with broad physiological implications, including neuronal development. In this review, we will summarize the genetic foundations behind RTT, and the variable degrees of protein stability exhibited by MeCP2 and its mutated versions. Also, past and emerging relationships that MeCP2 has with mRNA splicing, miRNA processing, and other non-coding RNAs (ncRNA) will be explored, and we suggest that these molecules could be missing links in understanding the epigenetic consequences incurred from genetic ablation of this important chromatin modifier. Importantly, although MeCP2 is highly expressed in the brain, where it has been most extensively studied, the role of this protein and its alterations in other tissues cannot be ignored and will also be discussed. Finally, the additional complexity to RTT pathology introduced by structural and functional implications of the two MeCP2 isoforms (MeCP2-E1 and MeCP2-E2) will be described. Epigenetic therapeutics are gaining clinical popularity, yet treatment for Rett syndrome is more complicated than would be anticipated for a purely epigenetic disorder, which should be taken into account in future clinical contexts.

scholarly journals Gut–neuroimmune interactions: the unexpected role of the immune system in brain development

2019 ◽  
Vol 41 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Simon Spichak ◽  
Timothy G. Dinan ◽  
John F. Cryan
Keyword(s):  
Immune System ◽  
Brain Development ◽  
Neuronal Development ◽  
Inflammatory Responses ◽  
Later Life ◽  
Innate Immune ◽  
Brain Health ◽  
Cytokines And Chemokines ◽  
The Brain

How does the immune system impact brain development? The exciting and somewhat unexpected relationship between the immune system and the brain has become one of the most fascinating topics in neuroscience. Even though the immune system was initially implicated in resolving viral and bacterial threats, it is now becoming more evident that it also plays a role in processes in the brain, both under healthy and pathological conditions. This novel role of the immune system in brain health has been implicated in various psychopathologies where neurodevelopment, stress and mood are central. In particular, its role in healthy brain development is becoming more evident, and understanding neuroimmune communication is becoming crucial in treating neurodevelopmental and mood disorders in later life. In the brain, glia function as part of the innate immune system and are programmed to respond to pathogens and physical injury. They also play an important role in neuronal development and pruning. These cells communicate with and respond to chemical signals, such as cytokines and chemokines, which can then initiate or downregulate inflammatory responses. Finally, the trillions of microbes residing in the gut can also stimulate cytokine and chemokine responses in the periphery and play an important role in both immunity and brain development.

scholarly journals An Emerging Role of PRRT2 in Regulating Growth Cone Morphology

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2666
Author(s):  
Elisa Savino ◽  
Fabrizia Guarnieri ◽  
Jin-Wu Tsai ◽  
Anna Corradi ◽  
Fabio Benfenati ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Growth Cone ◽  
Hippocampal Neurons ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Growth Cones ◽  
Cone Morphology ◽  
Infantile Seizures ◽  
Cytoskeleton Dynamics

Mutations in the PRRT2 gene are the main cause for a group of paroxysmal neurological diseases including paroxysmal kinesigenic dyskinesia, episodic ataxia, benign familial infantile seizures, and hemiplegic migraine. In the mature central nervous system, the protein has both a functional and a structural role at the synapse. Indeed, PRRT2 participates in the regulation of neurotransmitter release, as well as of actin cytoskeleton dynamics during synaptogenesis. Here, we show a role of the protein also during early stages of neuronal development. We found that PRRT2 accumulates at the growth cone in cultured hippocampal neurons. Overexpression of the protein causes an increase in the size and the morphological complexity of growth cones. In contrast, the growth cones of neurons derived from PRRT2 KO mice are smaller and less elaborated. Finally, we demonstrated that the aberrant shape of PRRT2 KO growth cones is associated with a selective alteration of the growth cone actin cytoskeleton. Our data support a key role of PRRT2 in the regulation of growth cone morphology during neuronal development.

scholarly journals Drebrin Regulates Acetylcholine Receptor Clustering and Organization of Microtubules at the Postsynaptic Machinery

2021 ◽  
Vol 22 (17) ◽  
pp. 9387
Author(s):  
Paloma Alvarez-Suarez ◽  
Natalia Nowak ◽  
Anna Protasiuk-Filipunas ◽  
Hiroyuki Yamazaki ◽  
Tomasz J. Prószyński ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Acetylcholine Receptors ◽  
Neuromuscular Junctions ◽  
Microtubule Network ◽  
Postsynaptic Protein ◽  
Cultured Myotubes ◽  
The Brain

Proper muscle function depends on the neuromuscular junctions (NMJs), which mature postnatally to complex “pretzel-like” structures, allowing for effective synaptic transmission. Postsynaptic acetylcholine receptors (AChRs) at NMJs are anchored in the actin cytoskeleton and clustered by the scaffold protein rapsyn, recruiting various actin-organizing proteins. Mechanisms driving the maturation of the postsynaptic machinery and regulating rapsyn interactions with the cytoskeleton are still poorly understood. Drebrin is an actin and microtubule cross-linker essential for the functioning of the synapses in the brain, but its role at NMJs remains elusive. We used immunohistochemistry, RNA interference, drebrin inhibitor 3,5-bis-trifluoromethyl pyrazole (BTP2) and co-immunopreciptation to explore the role of this protein at the postsynaptic machinery. We identify drebrin as a postsynaptic protein colocalizing with the AChRs both in vitro and in vivo. We also show that drebrin is enriched at synaptic podosomes. Downregulation of drebrin or blocking its interaction with actin in cultured myotubes impairs the organization of AChR clusters and the cluster-associated microtubule network. Finally, we demonstrate that drebrin interacts with rapsyn and a drebrin interactor, plus-end-tracking protein EB3. Our results reveal an interplay between drebrin and cluster-stabilizing machinery involving rapsyn, actin cytoskeleton, and microtubules.

The Role of Mitochondria in the Genesis of Neuroaxonal Dystrophy in the Brains of Aging Mice

1975 ◽  
Vol 33 ◽  
pp. 372-373
Author(s):  
J.E. Johnson
Keyword(s):  
Electron Microscopy ◽  
Present Report ◽  
Light And Electron Microscopy ◽  
Dorsal Column ◽  
Neuroaxonal Dystrophy ◽  
Nucleus Gracilis ◽  
Dystrophic Axons ◽  
The Brain ◽  
Nucleus Cuneatus

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).

Restraint stress exacerbates carbon tetrachloride-induced liver injury in rats: A role of endogenous corticotropin-releasing factor (CRF) in the brain

2001 ◽  
Vol 120 (5) ◽  
pp. A715-A715
Author(s):  
Y NAKADE ◽  
M YONEDA ◽  
S TAKAMOTO ◽  
T ITO ◽  
S OKAMOTO ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Restraint Stress ◽  
Corticotropin Releasing Factor ◽  
The Brain

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto
Keyword(s):  
Cerebrospinal Fluid ◽  
Carboxylic Acid ◽  
Fibrinolytic Activity ◽  
Clinical Implications ◽  
Trans Form ◽  
Plate Method ◽  
Blood Samples ◽  
Fibrin Plate ◽  
The Brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

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