28 research outputs found

    Lack of kinase-independent activity of PI3Kγ in locus coeruleus induces ADHD symptoms through increased CREB signaling.

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    Although PI3Kγ has been extensively investigated in inflammatory and cardiovascular diseases, the exploration of its functions in the brain is just at dawning. It is known that PI3Kγ is present in neurons and that the lack of PI3Kγ in mice leads to impaired synaptic plasticity, suggestive of a role in behavioral flexibility. Several neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), involve an impairment of behavioral flexibility. Here, we found a previously unreported expression of PI3Kγ throughout the noradrenergic neurons of the locus coeruleus (LC) in the brainstem, serving as a mechanism that regulates its activity of control on attention, locomotion and sociality. In particular, we show an unprecedented phenotype of PI3Kγ KO mice resembling ADHD symptoms. PI3Kγ KO mice exhibit deficits in the attentive and mnemonic domains, typical hyperactivity, as well as social dysfunctions. Moreover, we demonstrate that the ADHD phenotype depends on a dysregulation of CREB signaling exerted by a kinase-independent PI3Kγ-PDE4D interaction in the noradrenergic neurons of the locus coeruleus, thus uncovering new tools for mechanistic and therapeutic research in ADHD

    A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication

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    The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension

    Targeting interleukin-1β protects from aortic aneurysms induced by disrupted transforming growth factor β signaling

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    Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs. This danger signal later recruited innate immunity in the adventitia through chemokine (C-C motif) ligand 2 (CCL2) and modified the mechanical properties of the aortic wall, thus favoring vessel dilation. SMC-specific Smad4 deletion in Il1r1- or Ccr2-null mice resulted in milder aortic pathology. A chronic treatment with anti-IL-1β antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-β signaling, such as those driven by SMAD4 mutations

    SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

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    Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation. Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients. Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups. Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS

    Users awareness of native advertising from Instagram media publishers: the effects of Instagram’s branded content tool on attitudes and behavioural intent

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    With an online experiment we examine the effects of this disclosure on ad recognition and the resulting attitude toward the advertised brand, attitude toward the advertising publisher, publisher credibility and intention to spread electronic word-of-mouth (eWOM). Findings from a sample of 231 participants show that exposure to a post with advertising disclosure through the Instagram disclosure tool leads to higher ad recognition compared to a post with no disclosure. However, ad recognition negatively affects attitude toward the brand, publisher credibility and intention to spread eWOM. The study was published on the Int. J. Internet Marketing and Advertising, Vol. 14, No. 1, 2020

    Users awareness of native advertising from Instagram media publishers: the effects of Instagram's branded content tool on attitudes and behavioural intent

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    The Federal Trade Commission stated that any kind of endorsement or promotion on Instagram should be clearly and conspicuously disclosed in order to avoid users' deceptions. Albeit the compulsoriness of this measure is still unclear, Instagram has introduced a branded content tool for paid sponsorship disclosure that clearly states the presence of a material connection between the brand and the publisher or influencer. With an online experiment we examine the effects of this disclosure on ad recognition and the resulting attitude toward the advertised brand, attitude toward the advertising publisher, publisher credibility and intention to spread electronic word-of-mouth (eWOM). Findings from a sample of 231 participants show that exposure to a post with advertising disclosure through the Instagram disclosure tool leads to higher ad recognition compared to a post with no disclosure. However, ad recognition negatively affects attitude toward the brand, publisher credibility and intention to spread eWOM.info:eu-repo/semantics/publishedVersio

    A Literature Review of Bullshit Receptivity: Perspectives for an informed policy making against misinformation

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    Since the publication of Pennycook and colleagues’ (2015) paper on the reception of pseudo-profound bullshit, the concept of bullshit (BS) receptivity has slowly gained interest as an individual characteristic of people with the tendency to be overly receptive of and sensitive to fake claims. This paper seeks to identify and discuss peer-reviewed literature that applies BS receptivity scales, to better define their role within the bigger picture of the characteristics of those individuals particularly prone to the reception of a whole range of outlandish beliefs. Considering the cross-cutting nature of the issue, we prompt the need for further empirical and applicative research, and underline that – with BS receptivity belonging to the set of determinants contributing to flawed decision-making in terms of spotting genuine from fake content – greater involvement of behavioral economists is desirable. We call for such involvement not only within the BS debate, but also in assisting policymakers in their hard task of developing tailored policy responses and digital literacy interventions to combat misinformation and disinformation at its roots

    The effect of influencer–product fit on advertising recognition and the role of an enhanced disclosure in increasing sponsorship transparency

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    Many brands are now working on Instagram to promote, showcase their products and services, and benefit from the potentialities of Influencer Marketing. A detailed investigation of the effects of Instagram influencer advertising on the influencer-related outcomes is thus becoming urgent. The present study addresses a conceptual model in which the fit influencer–product congruence and the role of a more prominent disclosure are explored with respect to ad recognition, sponsorship transparency and influencer-related outcomes. Findings from a 2 (disclosure prominence: high vs. low) 2 (influencer-product congruence: high vs. low) between participants experimental design first show a positive effect of influencer product fit on attitude, credibility and continuance intention to follow the influencer. Moreover, a prominent disclosure enhances users’ perceived sponsorship transparency when the higher congruence makes it harder to discern a genuine endorsement from a sponsored one. Finally, we disentangle the mediating effects of ad recognition and sponsorship transparency between influencer–product congruence and the influencer-related outcomes

    The effect of influencer–product fit on advertising recognition and the role of an enhanced disclosure in increasing sponsorship transparency

    No full text
    The present study addresses a conceptual mo el in hich the fit influencer–product congruence and the role of a more prominent disclosure are explored with respect to ad ecognition, sponsorship transparency and influencer-related outcomes. Findings from a 2 (disclosure prominence: high vs. low) ? 2 (influencer- product congruence: high vs. low) between participants experimental design first show a positive effect of influencer product fit on attitude, credibility and continuance intention to follow the influencer. Moreover, a prominent disclosure enhances users’ perceived sponsorship transparency when the higher congruence makes it harder to discern a genuine endorsement from a sponsored one. Finally, we disentangle the mediating effects of ad recognition and sponsorship transparency between influencer–product congruence and the influencer-related outcomes. The study was published in the International Journal of Advertising. The Review of Marketing Communications Volume 40, 2021 - Issue 5

    Virtual vs. human influencer: Effects on users’ perceptions and brand outcomes

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    In this study, we compare users’ perceptions of influencer and brand- related variables after exposure to what was alleged to be either a human or a VI. Findings from an online experiment (N = 238) show that disclosing the AI nature of the influencer does not affect influencer and brand perceptions, nor the purchase intention. Moreover, results show that - despite VI’s objective lack of capacity to experience and feel - its acceptance is not hindered by an emotion-based, hedonic communicative style. Our results suggest that, in the specific case of VIs, individuals do not seem to apply different evaluation schemata for humans and AIs, supporting the use of this specific AI-based technology for commercial purposes
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