Canine muscle cell culture and consecutive patch-clamp measurements - a new approach to characterize muscular diseases in dogs.

Background: The recognition of functional muscular disorders, (e.g. channelopathies like Myotonia) is rising in veterinary neurology.

Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis.

Background And Purpose: Amyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive paralysis of striated muscles due to the loss of upper and lower motor neurons. The disease leads to death within 2-5 years, mainly due to respiratory failure. The pathogenesis of ALS is still unexplained for the most part.

4-Chloropropofol enhances chloride currents in human hyperekplexic and artificial mutated glycine receptors.

Background: The mammalian neurological disorder hereditary hyperekplexia can be attributed to various mutations of strychnine sensitive glycine receptors. The clinical symptoms of "startle disease" predominantly occur in the newborn leading to convulsive hypertonia and an exaggerated startle response to unexpected mild stimuli. Amongst others, point mutations R271Q and R271L in the α1-subunit of strychnine sensitive glycine receptors show reduced glycine sensitivity and cause the clinical symptoms of hyperekplexia.

Speech therapy and communication device: impact on quality of life and mood in patients with amyotrophic lateral sclerosis.

Dysarthria has a drastic impact on the quality of life of ALS patients. Most patients suffering from dysarthria are offered speech therapy. Communication devices are prescribed less frequently.

Onset and spreading patterns of upper and lower motor neuron symptoms in amyotrophic lateral sclerosis.

Introduction: The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. There is ongoing discussion as to whether ALS is primarily a disease of UMNs or LMNs.

Methods: We performed a retrospective analysis of 189 ALS patients from our ALS outpatient database to investigate the different spreading patterns of UMN and LMN affection in disease progression in relation to the onset region.

Nerve compression syndromes in ALS: a retrospective analysis in 554 patients.

We retrospectively screened a large cohort of 554 ALS patients with regard to documented nerve compression syndromes and identified 23 patients, mostly with carpal tunnel syndrome. Patients could be subdivided into three groups. Group A comprised 13 patients in whom nerve compression was apparently confused with early ALS signs.

[Quantitative study on cultivation of canine myoblasts].

Skeletal muscle cell culture is an important tool to discover the pathogenesis of rare canine neuromuscular diseases. The aim of the current study was to improve an existing clinical protocol to extract and cultivate canine myoblasts by using different enzymes for tissue digestion. The contamination of the mixed culture with fibrocytes should be minimized, a higher number of myoblasts with a shorter lag period should be gained and the influence of transport length on the myoblast numbers should be assessed.

Modulation of synaptic transmission and analysis of neuroprotective effects of valproic Acid and derivates in rat embryonic motoneurons.

Amyotrophic lateral sclerosis is a devastating motoneuron disorder for which no effective treatment exists. There is some evidence for neuroprotective effects of valproic acid (VPA). The beneficial effects, however, are limited due to the adverse effects of VPA.

Changes in extracellular pH affect glycine receptor channels expressed in HEK 293 cells.

Glycine receptors are expressed throughout the central nervous system working for inhibitory neurotransmission. Since fluctuations of the blood pH value occur under certain physiological and pathological conditions, we investigated the influence of the extracellular pH on glycine homomeric and heteromeric receptor functions using patch clamp in combination with the fast agonist application technique. Our results demonstrated that both alpha1 homomeric and alpha 1 beta heteromeric glycine receptors were remarkably inhibited under acidic extracellular pH.

Characterization and differentiation potential of rat ventral mesencephalic neuronal progenitor cells immortalized with SV40 large T antigen.

Neuronal progenitor cells (NPCs) possess high potential for use in regenerative medicine. To overcome their limited mitotic competence, various immortalization strategies have been applied that allow their prolonged maintenance and expansion in vitro. Such immortalized cells can be used for the design and discovery of new cell-based therapies for neurodegenerative diseases, such as Parkinson's disease.

The interaction of the neuroprotective compounds riluzole and phenobarbital with AMPA-type glutamate receptors: a patch-clamp study.

Background: Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors is a promising pharmacological strategy in the treatment of neurodegenerative diseases. The aim of the study is to elucidate if there are direct interactions of riluzole and phenobarbital with AMPA-type receptor channels and to determinethe molecular pharmacological mechanisms.

Methods: The patch-clamp technique was used combining an ultrafast solution exchange system to investigate the interaction of riluzole and phenobarbital with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y).

Synaptic currents and transmitter responses in human NT2 neurons differentiated in aggregate culture.

Postmitotic neurons were generated from the human NT2 teratocarcinoma cell line in a novel cell aggregate differentiation procedure. The NT2 model neurons express punctate immunoreactivity for synapsin and for cell markers related to GABAergic and glutamatergic neurotransmission. Using the outside-out patch-clamp configuration, we characterized the kinetics of currents elicited by a rapid application of the amino acid neurotransmitters.

Interaction of androsterone and progesterone with inhibitory ligand-gated ion channels: a patch clamp study.

Gamma-aminobutyric acid receptor type A (GABA(A)) receptor channels mediate fast inhibitory neurotransmission throughout the central nervous system while the expression of ionotropic glycine receptors is mainly restricted to the spinal cord and brain stem. Neuroactive steroids are well known as positive allosteric modulators of GABA(A) receptor function. Furthermore, there have been hints for an interaction of neuroactive steroids with ionotropic glycine receptors.

Changes of resting state brain networks in amyotrophic lateral sclerosis.

The defining feature of amyotrophic lateral sclerosis is degeneration of upper and lower motor neurons but extramotor involvement, evidenced for example by executive dysfunction, has also been demonstrated. Here we employed a novel functional imaging approach, the analysis of resting state activity, followed by the definition of functionally connected brain networks by independent component analysis (ICA) to assess differences between ALS patients (n=20) and healthy controls (n=20). ICA analysis revealed 5 typical brain networks among which the so-called default mode network and the sensori-motor network showed distinct differences between patients and controls.

Topical antiseptics for the treatment of sore throat block voltage-gated neuronal sodium channels in a local anaesthetic-like manner.

Lozenges for the treatment of sore throat provide relief of discomfort in cases of oral inflammation. This effect has not been fully explained so far. Here, we have examined the proposition that key components of pharmaceutical preparations for the treatment of sore throat which are routinely regarded antiseptics might have sodium channel-blocking, i.

Decreased brain activation to tongue movements in amyotrophic lateral sclerosis with bulbar involvement but not Kennedy syndrome.

Neuroimaging studies in amyotrophic lateral sclerosis (ALS) investigating movements of the hands have in general found increased activation compared to healthy controls, which has been interpreted in terms of cortical adaptation as a result of corticospinal tract damage. Here, we investigated brain activations to vertical tongue movements using functional MRI at 3 tesla. Whereas healthy controls, patients with Kennedy syndrome, and ALS patients without bulbar involvement showed robust and indistinguishable activations in pre- and postcentral areas and the thalamus, ALS patients with bulbar involvement showed a significant decrease of cortical activity and missing thalamic activity.

Analysis of neuroprotective effects of valproic acid on primary motor neurons in monoculture or co-cultures with astrocytes or Schwann cells.

Chronic dysregulation of the intracellular Ca(2+) homeostasis (excitotoxicity) is thought to contribute to the development of motor neuron diseases. Valproic acid (VPA) is widely used as an antiepileptic drug and acts mainly by inhibition of sodium channels and by enhancing the level of the inhibitory neurotransmitter gamma-aminobutyric acid. Neuroprotective capacities of VPA are supposed to arise also from the inhibition of histone deacetylases.

Modulation of glycine receptor function by the synthetic cannabinoid HU210.

Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. HU210 is a non-psychotropic, synthetic cannabinoid.

A long-term follow-up of botulinum toxin A in cervical dystonia.

Objective: Cervical dystonia (CD) is the most common form of adult-onset focal dystonia, and botulinum toxin A (BoNT-A) has become the first-line treatment for this condition.

Methods: In this work, we present data of 207 CD patients treated with BoNT-A for 6.7 +/- 3.

Treatment of phantom limb pain with botulinum toxin type A.

Introduction: Phantom limb pain and sensations are common in amputees. The pathophysiology remains unclear and the treatment difficult and often unsuccessful. Opioids are frequently used when non-narcotics have failed, but are not effective in many cases.

The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.

Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. Cannabidiol is a nonpsychotropic plant constituent of Cannabis sativa.

Preserved expression of fibroblast growth factor (FGF)-2 and FGF receptor 1 in brain and spinal cord of amyotrophic lateral sclerosis patients.

Impaired trophic support of motor neurons appears to be an important pathogenic factor in amyotrophic lateral sclerosis (ALS). We investigated the mRNA expression of the pluripotent fibroblast growth factor 2 (FGF-2) and its receptors in post mortem spinal cord of ALS and control patients. FGF-2 and FGF receptor (FGFR) 1 and 2 transcripts were first studied in the spinal cord using RT-PCR.

The non-anaesthetic propofol analogue 2,6-di-tert-butylphenol fails to modulate GABA(A) receptor function.

Modulation of inhibitory synaptic transmission within the central nervous system contributes considerably to the anaesthetic effects of propofol and its analogues in vivo. We have studied the effects of the non-anaesthetic propofol analogue 2,6-di-tert-butylphenol on rat alpha(1)beta(2)gamma(2) GABA(A) receptors expressed in a mammalian expression system (HEK 293 cells) using the whole-cell patch clamp technique. Our experiments showed that 2,6-di-tert-butylphenol completely lacks co-activation and direct activation of the inhibitory GABA(A) receptor.

A transmembrane residue influences the interaction of propofol with the strychnine-sensitive glycine alpha1 and alpha1beta receptor.

Background: Propofol, well known for its anesthetic effects, acts as a positive allosteric modulator of the alpha-aminobutyric acid type A (GABA(A)) receptor but also enhances the function of the glycine receptor. The GABA modulatory effects of propofol are influenced by an amino acid residue located within the second transmembrane domain (TM2) of the GABA(A) receptor beta subunit. In glycine alpha(1) subunits, the homologous residue (serine 267) affects the glycine modulatory actions of alcohols and alkane anesthetics.

Positive allosteric modulatory effects of ajulemic acid at strychnine-sensitive glycine alpha1- and alpha1beta-receptors.

The synthetic cannabinoid ajulemic acid (CT-3) is a potent cannabinoid receptor agonist which was found to reduce pain scores in neuropathic pain patients in the absence of cannabis-like psychotropic adverse effects. The reduced psychotropic activity of ajulemic acid has been attributed to a greater contribution of peripheral CB receptors to its mechanism of action as well as to non-CB receptor mechanisms. Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury.