Ribosomal Protein S6 Phosphorylation Is Involved in Novelty-Induced Locomotion, Synaptic Plasticity and mRNA Translation

Puighermanal, Emma; Biever, Anne; Pascoli, Vincent; Melser, Su; Pratlong, Marine; Cutando, Laura; Rialle, Stéphanie; Séverac, Dany; Boubaker-Vitre, Jihane; Meyuhas, Oded; Marsicano, Giovanni; Lüscher, Christian; Valjent, Emmanuel

doi:10.3389/fnmol.2017.00419

Cited by 31 publications

(26 citation statements)

References 60 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The levels of c-Fos/ChAT activation were lower in the contralateral than ipsilateral DMX [F(2, 12)=9.642, P≤ 0.001], while significantly more activation was still observed in the pVNS compared to naïve [F(2, 12)=66.68, P≤ 0.001], but not sham mice (17±2 ipsilateral, 7±3 contralateral) [F(2, 12)=66.68, P =0.01]. In addition to c-Fos we also assessed ribosomal protein S6 phosphorylation as a marker to track neuronal activity [21]. pVNS treatment also resulted in increased levels of Phospho-S6 in the brainstem (337±53) as compared to sham mice (68±31, P ≤0.05; Suppl.…”

Section: Resultsmentioning

confidence: 99%

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice

et al. 2019

View full text Add to dashboard Cite

Background: The vagus nerve is involved in regulating immunity and resolving inflammation. Current strategies aimed at modulating neuroinflammation and cognitive decline, in many cases, are limited and ineffective. Objective: We sought to develop a minimally invasive, targeted, vagus nerve stimulation approach (pVNS), and we tested its efficacy with respect to microglial activation and amelioration of cognitive dysfunction following lipopolysaccharide (LPS) endotoxemia in mice. Methods: We stimulated the cervical vagus nerve in mice using an ultrasound-guided needle electrode under sevoflurane anesthesia. The concentric bipolar needle electrode was percutaneously placed adjacent to the carotid sheath and stimulation was verified in real-time using bradycardia as a biomarker. Activation of vagal fibers was confirmed with immunostaining in relevant brainstem structures, including the dorsal motor nucleus and nucleus tractus solitarius. Efficacy of pVNS was evaluated following administration of LPS and analyses of changes in inflammation and behavior. Results: pVNS enabled stimulation of the vagus nerve as demonstrated by changes in bradycardia and histological evaluation of c-Fos and choline acetyltransferase expression in brainstem nuclei. Following LPS administration, pVNS significantly reduced plasma levels of tumor necrosis factor-α at 3 h post-injection. pVNS prevented LPS-induced hippocampal microglial activation as analyzed by changes in Iba-1 immunoreactivity, including cell body enlargement and shortened ramifications. Cognitive dysfunction following endotoxemia was also restored by pVNS. Conclusion: Targeted cervical VNS using this novel percutaneous approach reduced LPS-induced systemic and brain inflammation and significantly improved cognitive responses. These results provide a novel therapeutic approach using bioelectronic medicine to modulate neuro-immune interactions that affect cognition.

show abstract

Section: Resultsmentioning

confidence: 99%

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…DS and Acb were dissected and stored at −80°C until further use. Tissue (n = 20-22/brain area) was homogenized and processed as previously described 52 in order to measure CI (EC 1.6.5.3) and CS (E.C. 2.3.3.1).…”

Section: Methodsmentioning

confidence: 99%

Functional and molecular heterogeneity of D2R neurons along dorsal ventral axis in the striatum

et al. 2020

Self Cite

View full text Add to dashboard Cite

Action control is a key brain function determining the survival of animals in their environment. In mammals, neurons expressing dopamine D2 receptors (D2R) in the dorsal striatum (DS) and the nucleus accumbens (Acb) jointly but differentially contribute to the fine regulation of movement. However, their region-specific molecular features are presently unknown. By combining RNAseq of striatal D2R neurons and histological analyses, we identified hundreds of novel region-specific molecular markers, which may serve as tools to target selective subpopulations. As a proof of concept, we characterized the molecular identity of a subcircuit defined by WFS1 neurons and evaluated multiple behavioral tasks after its temporally-controlled deletion of D2R. Consequently, conditional D2R knockout mice displayed a significant reduction in digging behavior and an exacerbated hyperlocomotor response to amphetamine. Thus, targeted molecular analyses reveal an unforeseen heterogeneity in D2R-expressing striatal neuronal populations, underlying specific D2R's functional features in the control of specific motor behaviors.

show abstract

“…Real-time PCR was carried out in a 10 µl reaction using SYBR Green PCR Master Mix Rocheaccording to the manufacturer's protocol with a QuantStudio 12K Flex Real-Time PCR System (Applied Biosystems). The following primers previously described (Cutando et al, 2013;Puighermanal et al, 2017) specific for mouse were used: Cnr1 (sense, 5'-CCTGGGAAGTGTCATCTTTGT -3'; antisense, 5'-GGTAACCCCACCCAGTTTGA -3') and β-actin (sense, 5'-CGTGAAAAGATGACCCAGATCA-3' ; antisense, 5'-CACAGCCTGGATGGCTACGT-3'). Quantification was performed by using the comparative CT Method (ΔΔCT Method).…”

Section: Quantitative Real-time Pcr Analysismentioning

confidence: 99%

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome

Navarro-Romero

Vázquez-Oliver

Gomis-González

et al. 2019

Neurobiology of Disease

View full text Add to dashboard Cite

Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. However, the involvement of the endocannabinoid system in the pathogenesis of Down syndrome has not been explored before. We used the best-characterized preclinical model of Down syndrome, the segmentally trisomic Ts65Dn model. In male Ts65Dn mice, cannabinoid type-1 receptor (CB1R) expression was enhanced and its function increased in hippocampal excitatory terminals. Knockdown of CB1R in the hippocampus of male Ts65Dn mice restored hippocampal-dependent memory. Concomitant with this result, pharmacological inhibition of CB1R restored memory deficits, hippocampal synaptic plasticity and adult neurogenesis in the subgranular zone of the dentate gyrus. Notably, the blockade of CB1R also normalized hippocampal-dependent memory in female Ts65Dn mice. To further investigate the mechanisms involved, we used a second transgenic mouse model overexpressing a single gene candidate for Down syndrome cognitive phenotypes, the dual specificity tyrosinephosphorylation-regulated kinase 1A (DYRK1A). CB1R pharmacological blockade similarly improved cognitive performance, synaptic plasticity and neurogenesis in transgenic male Dyrk1A mice. Our results identify CB1R as a novel druggable target potentially relevant for the improvement of cognitive deficits associated with Down syndrome.

show abstract

Ribosomal Protein S6 Phosphorylation Is Involved in Novelty-Induced Locomotion, Synaptic Plasticity and mRNA Translation

Cited by 31 publications

References 60 publications

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice

Functional and molecular heterogeneity of D2R neurons along dorsal ventral axis in the striatum

Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome

Contact Info

Product

Resources

About