scholarly journals Nonsense mutation in CFAP43 causes normal-pressure hydrocephalus with ciliary abnormalities

Neurology ◽  
2019 ◽  
Vol 92 (20) ◽  
pp. e2364-e2374 ◽  
Author(s):  
Yoshiro Morimoto ◽  
Shintaro Yoshida ◽  
Akira Kinoshita ◽  
Chisei Satoh ◽  
Hiroyuki Mishima ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Loss Of Function ◽  
Japanese Family ◽  
Whole Exome ◽  
Cilia And Flagella ◽  
The Brain ◽  
Morphologic Abnormality ◽  
Deficient Mice

ObjectiveTo identify genes related to normal-pressure hydrocephalus (NPH) in one Japanese family with several members with NPH.MethodsWe performed whole-exome sequencing (WES) on a Japanese family with multiple individuals with NPH and identified a candidate gene. Then we generated knockout mouse using CRISPR/Cas9 to confirm the effect of the candidate gene on the pathogenesis of hydrocephalus.ResultsIn WES, we identified a loss-of-function variant in CFAP43 that segregated with the disease. CFAP43 encoding cilia- and flagella-associated protein is preferentially expressed in the testis. Recent studies have revealed that mutations in this gene cause male infertility owing to morphologic abnormalities of sperm flagella. We knocked out mouse ortholog Cfap43 using CRISPR/Cas9 technology, resulting in Cfap43-deficient mice that exhibited a hydrocephalus phenotype with morphologic abnormality of motile cilia.ConclusionOur results strongly suggest that CFAP43 is responsible for morphologic or movement abnormalities of cilia in the brain that result in NPH.

scholarly journals Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 357
Author(s):  
Mojca Trstenjak Prebanda ◽  
Petra Matjan-Štefin ◽  
Boris Turk ◽  
Nataša Kopitar-Jerala
Keyword(s):  
Mouse Model ◽  
Redox Homeostasis ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Altered Expression ◽  
Lps Challenge ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy ◽  
The Brain ◽  
Deficient Mice

Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease.

In vivo viscoelastic properties of the brain in normal pressure hydrocephalus

2010 ◽  
pp. n/a-n/a ◽  
Author(s):  
Kaspar-Josche Streitberger ◽  
Edzard Wiener ◽  
Jan Hoffmann ◽  
Florian Baptist Freimann ◽  
Dieter Klatt ◽  
...  
Keyword(s):  
Normal Pressure Hydrocephalus ◽  
Viscoelastic Properties ◽  
Normal Pressure ◽  
The Brain

Cerebral cysticercosis with aqueductal obstruction

1980 ◽  
Vol 53 (2) ◽  
pp. 252-255 ◽  
Author(s):  
Tung Pui Poon ◽  
Edward J. Arida ◽  
Wolodymyr P. Tyschenko
Keyword(s):  
Intracranial Hypertension ◽  
Brain Stem ◽  
Normal Pressure Hydrocephalus ◽  
Signs And Symptoms ◽  
Normal Pressure ◽  
Content Type ◽  
Neurological Signs ◽  
Cerebral Cysticercosis ◽  
The Brain ◽  
Fine Print

✓ The authors report a case of cerebral cysticercosis which presented with generalized nonspecific neurological signs and symptoms attributed to acute aqueductal obstruction, with concomitant intracranial hypertension. These were characteristic intracranial calcifications along with angiographically demonstrated signs of hydrocephalus. Contrast encephalography clearly demonstrated aqueductal obstruction. Pathologically, the aqueductal obstruction was shown to be due to parasitic invasion of the brain stem with compression of the aqueduct. The presence of typical intracranial calcification in conjunction with either obstructive or normal-pressure hydrocephalus should alert the observer to the possibility of cerebral cysticercosis.

Modelling Normal Pressure Hydrocephalus as a ‘Two-Hit’ Disease Using Multiple-Network Poroelastic Theory

2010 ◽  
Author(s):  
Brett Tully ◽  
Yiannis Ventikos
Keyword(s):  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Brain Parenchyma ◽  
Strongly Correlated ◽  
Clinical Markers ◽  
Cerebral Diseases ◽  
Spatio Temporal ◽  
Multiple Network ◽  
Poroelastic Theory ◽  
The Brain

The evolution of many cerebral diseases such as Alzheimer’s and Parkinson’s Disease, Hydrocephalus, Cerebral Oedema, Stroke, and Tumour are strongly correlated to a change in the transport properties of fluid in the brain. This research proposes a novel application of Multiple-Network Poroelastic Theory (MPET) to investigate cerebral hydrodynamics through a detailed investigation of multiscalar, spatio-temporal transport of fluid between the cerebral blood, cerebrospinal fluid (CSF) and brain parenchyma. Specifically, MPET is used to interrogate the clinical markers of Normal Pressure Hydrocephalus (NPH).

scholarly journals Defective AMH signaling disrupts GnRH neuron development and function and contributes to hypogonadotropic hypogonadism

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Samuel Andrew Malone ◽  
Georgios E Papadakis ◽  
Andrea Messina ◽  
Nour El Houda Mimouni ◽  
Sara Trova ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Abnormal Development ◽  
Loss Of Function ◽  
Neuron Development ◽  
Motility Factor ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Whole Exome ◽  
Gnrh Neurons ◽  
And Function ◽  
Deficient Mice

Congenital hypogonadotropic hypogonadism (CHH) is a condition characterized by absent puberty and infertility due to gonadotropin releasing hormone (GnRH) deficiency, which is often associated with anosmia (Kallmann syndrome, KS). We identified loss-of-function heterozygous mutations in anti-Müllerian hormone (AMH) and its receptor, AMHR2, in 3% of CHH probands using whole-exome sequencing. We showed that during embryonic development, AMH is expressed in migratory GnRH neurons in both mouse and human fetuses and unconvered a novel function of AMH as a pro-motility factor for GnRH neurons. Pathohistological analysis of Amhr2-deficient mice showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in reduced fertility in adults. Our findings highlight a novel role for AMH in the development and function of GnRH neurons and indicate that AMH signaling insufficiency contributes to the pathogenesis of CHH in humans.

Computed tomography of the brain in the diagnosis of and prognosis in normal pressure hydrocephalus

1989 ◽  
Vol 31 (2) ◽  
pp. 160-165 ◽  
Author(s):  
C. Wikkels� ◽  
H. Andersson ◽  
C. Blomstrand ◽  
M. Matousek ◽  
P. Svendsen
Keyword(s):  
Computed Tomography ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
The Brain
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