Differential protection of neuromuscular sensory and motor axons and their endings in Wld mutant mice

Oyebode, Oyinlola; Hartley, Robert W.; Singhota, J.; Thomson, David; Ribchester, Richard R.

doi:10.1016/j.neuroscience.2011.10.020

Cited by 10 publications

(20 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Gamma-and a-motoneurons differ in their role during motor behavior, in their morphology, in their conduction velocity, in their central and peripheral pattern of connectivity, and in their response to orthograde Wallerinan degeneration (for reviews see Banks, 1994;Kanning et al, 2010;Oyebode et al, 2012). While a-motoneurons have a large cell body, constitute approximately 70% of all motoneurons and receive precise Ia-derived monosynaptic proprioceptive sensory input, c-motoneurons have small cell bodies, lack direct sensory input from proprioceptive afferents and have unique electrophysiological properties (Burke et al, 1977;Friese et al, 2009;Enjin et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles

Zhang

Lin

Karakatsani

et al. 2014

Eur J of Neuroscience

View full text Add to dashboard Cite

Intrafusal fibers of muscle spindles are innervated in the central region by afferent sensory axons and at both polar regions by efferent γ-motoneurons. We previously demonstrated that both neuron-muscle contact sites contain cholinergic synapse-like specialisation, including aggregates of the nicotinic acetylcholine receptor (AChR). In this study we tested the hypothesis that agrin and its receptor complex (consisting of LRP4 and the tyrosine kinase MuSK) are involved in the aggregation of AChRs in muscle spindles, similar to their role at the neuromuscular junction. We show that agrin, MuSK and LRP4 are concentrated at the contact site between the intrafusal fibers and the sensory- and γ-motoneuron, respectively, and that they are expressed in the cell bodies of proprioceptive neurons in dorsal root ganglia. Moreover, agrin and LRP4, but not MuSK, are expressed in γ-motoneuron cell bodies in the ventral horn of the spinal cord. In agrin- and in MuSK-deficient mice, AChR aggregates are absent from the polar regions. In contrast, the subcellular concentration of AChRs in the central region where the sensory neuron contacts the intrafusal muscle fiber is apparently unaffected. Skeletal muscle-specific expression of miniagrin in agrin(-/-) mice in vivo is sufficient to restore the formation of γ-motoneuron endplates. These results show that agrin and MuSK are major determinants during the formation of γ-motoneuron endplates but appear dispensable for the aggregation of AChRs at the central region. Our results therefore suggest different molecular mechanisms for AChR clustering within two domains of intrafusal fibers.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles

Zhang

Lin

Karakatsani

et al. 2014

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…The protein expression patterns in neurites of different neuronal types (e.g., peripheral/central or human/mouse) can differ, and this will also affect the abundance of modulators of axonal degeneration [19][20][21]. Therefore, it appears advisable to choose a toxicological model system that matches its pathological reference system (e.g., human peripheral axons) as closely as possible, as far as the type of neurons and the species of their origin are concerned.…”

Section: Introductionmentioning

confidence: 99%

Stem Cell-Derived Immature Human Dorsal Root Ganglia Neurons to Identify Peripheral Neurotoxicants

Hoelting

Klima

Karreman

et al. 2016

Stem Cells Translational Medicine

116

View full text Add to dashboard Cite

Safety sciences and the identification of chemical hazards have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically important field of peripheral neurotoxicity is still largely unexplored. A two-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as a functional parameter highly sensitive to disturbances by toxicants was used as an endpoint reflecting specific neurotoxicity. The differentiation of cells toward dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as a first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for the prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants and neurite growth enhancers were correctly identified. Various classes of chemotherapeutic agents causing human peripheral neuropathies were identified, and they were missed when tested on human central neurons. The PeriTox test we established shows the potential of human stem cells for clinically relevant safety testing of drugs in use and of new emerging candidates. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:476-487 SIGNIFICANCEThe generation of human cells from pluripotent stem cells has aroused great hopes in biomedical research and safety sciences. Neurotoxicity testing is a particularly important application for stem cell-derived somatic cells, as human neurons are hardly available otherwise. Also, peripheral neurotoxicity has become of major concern in drug development for chemotherapy. The first neurotoxicity test method was established based on human pluripotent stem cell-derived peripheral neurons. The strategies exemplified in the present study of reproducible cell generation, cell function-based test system establishment, and assay validation provide the basis for a drug safety assessment on cells not available otherwise.

show abstract

“…Виявлена нами деструкція окремих мієлінових нервових волокон викликає денервацію м'язових волокон, що проявляється зменшенням кількості нейролемоцитів у ділянці нервово-м'язових закінчень і аргірофілією їх ядер. Такі зміни спостерігали інші дослідники за порушення структури нервово-м'язових закінчень як при цукровому діабеті (Bril, 2014;Ignacio and Felix, 2016), так і за захворювань іншого генезу (Muntoni, 2012;Oyebode et al, 2012;Silinsky, 2013).…”

Section: обговоренняunclassified

Left ventricular diastolic function in patients with obstructive sleep apnoea syndrome and obesity

Luchynskyi

Luchinskyi

Shcherba

et al. 2017

Regul. Mech. Biosyst.

View full text Add to dashboard Cite

Obstructive sleep apnea syndrome (OSAS) is a chronic disease characterized by recurrent episodes of complete or partial obstruction of the upper airways during sleep and results in sleep fragmentation, night hypoxemia, and daytime sleepiness. The aim of this study was to investigate the state of left ventricular diastolic function in patients with first diagnosed COAS and obesity and to define the determinants of diastolic dysfunction in this category of patients. There were 46 patients (33 men and 13 women) with OSAS and obesity and 52 patients with obesity without OSAS enrolled in the study. The control group included 22 practically healthy individuals. Each patient underwent assessment of body mass index (BMI), 24-hour ambulatory blood pressure monitoring, cardiorespiratory monitoring, transthoracic echocardiography. We found that patients with OSAS and obesity had significant impairment of diastolic function in comparison with patients with obesity without OSAS, which manifested itself in decreasing of E/A ratio, increasing deceleration time and increasing isovolumic relaxation time. Increasing body mass index and increasing level of hypoxia lead to impairment of diastolic dysfunction. Diastolic dysfunction was diagnosed in 4 obese patients without OSAS and in 17 patients with OSAS and obesity. All patients with diastolic dysfunction had second or third stage obesity and severe OSAS. Left ventricular hypertrophy was diagnosed in 9 patients with OSAS and obesity. Patients with concentric hypertrophy had significantly lower E/A in comparison with patients without hypertrophy or with concentric remodeling. We found that the deceleration time has positive correlation with body mass index and desaturation index and negative correlation with min SaO2. Isovolumic relaxation time correlated only with desaturation index. According to the results of univariable regression analysis, five variables were allocated: body mass index, age, desaturation index, index apnea-hypopnea and left ventricular mass index. The multivariate analyses, after adjustment for age and sex and stepwise regression, showed that only the desaturation index was an independent predictor of left ventricular diastolic dysfunction in patients with OSAS and obesity. Obstructive sleep apnea syndrome combined with obesity leads to a deterioration of the diastolic function of the left ventricle even in patients without cardio-vascular diseases. The state of the diastolic function of the left ventricule worsens with an increase in the severity of hypoxic disorders in the syndrome of obstructive sleep apnea and with the degree of obesity. In multivariate regression analysis, the desaturation index was a predictor of left ventricular diastolic dysfunction in patients with obstructive sleep apnea syndrome and obesity.

show abstract

Differential protection of neuromuscular sensory and motor axons and their endings in Wld mutant mice

Cited by 10 publications

References 73 publications

Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles

Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles

Stem Cell-Derived Immature Human Dorsal Root Ganglia Neurons to Identify Peripheral Neurotoxicants

Left ventricular diastolic function in patients with obstructive sleep apnoea syndrome and obesity

Contact Info

Product

Resources

About