151 research outputs found
In situ imaging reveals properties of purinergic signalling in trigeminal sensory ganglia in vitro
Functional Genomics of Muscle, Nerve and Brain Disorder
Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists
Background Migraine is a common brain disorder that predominantly affects women. Migraine pain seems mediated by the activation of mechanosensitive channels in meningeal afferents. Given the role of transient receptor potential melastatin 3 (TRPM3) channels in mechanical activation, as well as hormonal regulation, these channels may play a role in the sex difference in migraine. Therefore, we investigated whether nociceptive firing induced by TRPM3 channel agonists in meningeal afferents was different between male and female mice. In addition, we assessed the relative contribution of mechanosensitive TRPM3 channels and that of mechanosensitive Piezo1 channels and transient receptor potential vanilloid 1 (TRPV1) channels to nociceptive firing relevant to migraine in both sexes. Methods Ten- to 13-week-old male and female wildtype (WT) C57BL/6 J mice were used. Nociceptive spikes were recorded directly from nerve terminals in the meninges in the hemiskull preparations. Results Selective agonists of TRPM3 channels profoundly activated peripheral trigeminal nerve fibres in mouse meninges. A sex difference was observed for nociceptive firing induced by either PregS or CIM0216, both agonists of TRPM3 channels, with the induced firing being particularly prominent for female mice. Application of Yoda1, an agonist of Piezo1 channels, or capsaicin activating TRPV1 channels, although also leading to increased nociceptive firing of meningeal fibres, did not reveal a sex difference. Cluster analyses of spike activities indicated a massive and long-lasting activation of TRPM3 channels with preferential induction of large-amplitude spikes in female mice. Additional spectral analysis revealed a dominant contribution of spiking activity in the alpha- and beta-ranges following TRPM3 agonists in female mice. Conclusions Together, we revealed a specific mechanosensitive profile of nociceptive firing in females and suggest TRPM3 channels as a potential novel candidate for the generation of migraine pain, with particular relevance to females.Functional Genomics of Muscle, Nerve and Brain Disorder
Overexpressed Na(V)1.7 channels confer hyperexcitability to in vitro trigeminal sensory neurons of Ca(V)2.1 mutant hemiplegic migraine mice
Trigeminal sensory neurons of transgenic knock-in (KI) mice expressing the R192Q missense mutation in the alpha 1A subunit of neuronal voltage-gated Ca(V)2.1 Ca2+ channels, which leads to familial hemiplegic migraine type 1 (FHM1) in patients, exhibit a hyperexcitability phenotype. Here, we show that the expression of Na(V)1.7 channels, linked to pain states, is upregulated in KI primary cultures of trigeminal ganglia (TG), as shown by increased expression of its alpha 1 subunit. In the majority of TG neurons, Na(V)1.7 channels are co-expressed with ATP-gated P2X3 receptors (P2X3R), which are important nociceptive sensors. Reversing the trigeminal phenotype with selective Ca(V)2.1 channel inhibitor omega-agatoxin IVA inhibited Na(V)1.7 overexpression. Functionally, KI neurons revealed a TTX-sensitive inward current of larger amplitude that was partially inhibited by selective Na(V)1.7 blocker Tp1a. Under current-clamp condition, Tp1a raised the spike threshold of both wild-type (WT) and KI neurons with decreased firing rate in KI cells. Na(V)1.7 activator OD1 accelerated firing in WT and KI neurons, a phenomenon blocked by Tp1a. Enhanced expression and function of Na(V)1.7 channels in KI TG neurons resulted in higher excitability and facilitated nociceptive signaling. Co-expression of Na(V)1.7 channels and P2X3Rs in TGs may explain how hypersensitivity to local stimuli can be relevant to migraine.Paroxysmal Cerebral Disorder
Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists
Background Migraine is a common brain disorder that predominantly affects women. Migraine pain seems mediated by the activation of mechanosensitive channels in meningeal afferents. Given the role of transient receptor potential melastatin 3 (TRPM3) channels in mechanical activation, as well as hormonal regulation, these channels may play a role in the sex difference in migraine. Therefore, we investigated whether nociceptive firing induced by TRPM3 channel agonists in meningeal afferents was different between male and female mice. In addition, we assessed the relative contribution of mechanosensitive TRPM3 channels and that of mechanosensitive Piezo1 channels and transient receptor potential vanilloid 1 (TRPV1) channels to nociceptive firing relevant to migraine in both sexes. Methods Ten- to 13-week-old male and female wildtype (WT) C57BL/6 J mice were used. Nociceptive spikes were recorded directly from nerve terminals in the meninges in the hemiskull preparations. Results Selective agonists of TRPM3 channels profoundly activated peripheral trigeminal nerve fibres in mouse meninges. A sex difference was observed for nociceptive firing induced by either PregS or CIM0216, both agonists of TRPM3 channels, with the induced firing being particularly prominent for female mice. Application of Yoda1, an agonist of Piezo1 channels, or capsaicin activating TRPV1 channels, although also leading to increased nociceptive firing of meningeal fibres, did not reveal a sex difference. Cluster analyses of spike activities indicated a massive and long-lasting activation of TRPM3 channels with preferential induction of large-amplitude spikes in female mice. Additional spectral analysis revealed a dominant contribution of spiking activity in the alpha- and beta-ranges following TRPM3 agonists in female mice. Conclusions Together, we revealed a specific mechanosensitive profile of nociceptive firing in females and suggest TRPM3 channels as a potential novel candidate for the generation of migraine pain, with particular relevance to females.Functional Genomics of Muscle, Nerve and Brain Disorder
THE EFFECTIVENESS OF FISHBOWL METHOD ON STUDENTS’ SPEAKING SKILL AT THE SECOND GRADE STUDENTS OF SMA N 8 CIREBON
AYU WULANDARI. THE EFFECTIVENESS OF FISHBOWL METHOD ON
STUDENTS’ SPEAKING SKILL AT THE SECOND GRADE STUDENTS OF
SMA N 8 CIREBON
In Indonesia English has drawn up by government as foreign language that
the students should master English language. In fact, the students still have
weakness in skill of English, especially in speaking skill. In this thesis, the writer
focuses on the students’ speaking skill as Y variable that they have any weakness
to master speaking skill. And the writer focuses on the fishbowl method as the X
variable that will help student to practice speaking English.
The aims of this research are to find out the students’ responses towards the
application of fishbowl method, to find out the students’ achievement of speaking
skill before and after using the application of fishbowl method and to find out the
effectiveness of fishbowl method to improve the students’ speaking skill
Looking forward the problem in speaking skill that students have the
weakness in this skill thus the writer offered fishbowl method which can be
effective teaching tools for modeling group processes that can improve the
students’ speaking skill and more active in classroom to practice speaking
English.
The research design is quantitative research and experiment research. To
know the response the application of fishbowl method, the writer uses
questionnaire. To know the students’ achievement speaking skill, the writer uses
two tests, pretest and posttest. The data was analyzed statistically by using
Microsoft Excel, ANA test4 and SPSS program V 2.2.0.
The result of the students’ response towards the application of fishbowl
method is 1237 with the percentage 82,5 %, it can be categorized strong response.
And the result of the students’ achievement in speaking skill between
experimental class and control class where Gain of experiment class get the mean
score 0.26, but the N-Gain of control class get the mean score 0.12 so that the
deviation is 0.14. It means that the experiment class is better than control class in
improving the students’ speaking skill. Then conclusion of this thesis is that the
alternative hypothesis (Ha) is received and the Null Hypothesis (Ho) is refused
where t-test < t-table or <0.05. It means that there is any significant effectiveness
of using fishbowl method to improve students’ speaking skill the second grade
students of SMA N 8 Cirebon
Funnel-freezing versus heat-stabilization for the visualization of metabolites by mass spectrometry imaging in a mouse stroke model
Functional Genomics of Muscle, Nerve and Brain Disorder
EEG-based visual deviance detection in freely behaving mice
The mouse is widely used as an experimental model to study visual processing. To probe how the visual system detects changes in the environment, functional paradigms in freely behaving mice are strongly needed. We developed and validated the first EEG-based method to investigate visual deviance detection in freely behaving mice. Mice with EEG implants were exposed to a visual deviant detection paradigm that involved changes in light intensity as standard and deviant stimuli. By subtracting the standard from the deviant evoked waveform, deviant detection was evident as bi-phasic negativity (starting around 70 ms) in the difference waveform. Additionally, deviance-associated evoked (beta/gamma) and induced (gamma) oscillatory responses were found. We showed that the results were stimulus-independent by applying a "flip-flop " design and the results showed good repeatability in an independent measurement. Together, we put forward a validated, easy-to-use paradigm to measure visual deviance processing in freely behaving mice.Functional Genomics of Muscle, Nerve and Brain Disorder
Early seizures and cerebral oedema after trivial head trauma associated with the CACNA1A S218L mutation
Migraine biomarkers in cerebrospinal fluid: a systematic review and meta-analysis
Analytical BioScience
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