Browsing Anatomy and Neuroscience - Journal Articles by Subject "Activation"
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- ItemAcute stress increases monocyte levels and modulates receptor expression in healthy females(Elsevier, 2021-05) van de Wouw, Marcel; Sichetti, Marzia; Long-Smith, Caitriona M.; Ritz, Nathaniel L.; Moloney, Gerard M.; Cusack, Anne-Marie; Berding, Kirsten; Dinan, Timothy G.; Cryan, John F.; Seventh Framework Programme; Science Foundation IrelandThere has been a growing recognition of the involvement of the immune system in stress-related disorders. Acute stress leads to the activation of neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells, such as monocytes. Even though acute stress/monocyte interactions have been wellcharacterized in mice, this is not the case for humans. As such, this study aimed to investigate whether acute stress modulates blood monocyte levels in a subtype-dependent manner and whether the receptor expression of stress-related receptors is affected in humans. Blood was collected from healthy female volunteers at baseline and 1 h after the socially evaluated cold pressor test, after which blood monocyte levels and receptor expression were assessed by flow cytometry. Our results reveal a stress-induced increase in blood monocyte levels, which was independent of monocyte subtypes. Furthermore, colony stimulating factor 1 receptor (CSF-1R) and CD29 receptor expression was increased, while CD62L showed a trend towards increased expression. These results provide novel insights into how acute stress affects the innate immune system.
- ItemMicrobial memories: sex-dependent impact of the gut microbiome on hippocampal plasticity(John Wiley and Sons Ltd, 2021-08) Darch, Henry T.; Collins, Michael K.; O'Riordan, Kenneth J.; Cryan, John F.; Science Foundation Ireland; Saks-Kavanaugh FoundationGerm-free rodents, raised in the absence of a measurable gut microbiome, have been a key model to study the microbiome-gut-brain axis. Germ-free mice exhibit marked behavioural and neurochemical differences to their conventionally raised counterparts. It is as yet unclear how these neurochemical differences lead to the behavioural differences. Here, we test the electrophysiological properties of hippocampal plasticity in adult germ-free mice and compare them to conventionally raised counterparts. Whilst basal synaptic efficacy and pre-synaptic short-term plasticity appear normal, we find a striking alteration of hippocampal long-term potentiation specifically in male germ-free slices. However, the spike output of these neurons remains normal along with altered input-output coupling, potentially indicating homeostatic compensatory mechanisms, or an altered excitation/inhibition balance. To our knowledge this is the first time the electrophysiological properties of the hippocampus have been assessed in a microbiome deficient animal. Our data indicate that the absence of a microbiome alters integration of dendritic signalling in the CA1 region in mice.
- ItemMolecular, biochemical and behavioural evidence for a novel oxytocin receptor and serotonin 2C receptor heterocomplex(Elsevier, 2021-02) Chruścicka, Barbara; Cowan, Caitlin S. M.; Wallace Fitzsimons, Shauna E.; Borroto-Escuela, Dasiel O.; Druelle, Clémentine; Stamou, Panagiota; Bergmann, Cristian A.; Dinan, Timothy G.; Slattery, David A.; Fuxe, Kjell; Cryan, John F.; Schellekens, Harriët; Science Foundation Ireland; Narodowym Centrum Nauki; Medicinska Forskningsrådet; HjärnfondenThe complexity of oxytocin-mediated functions is strongly associated with its modulatory effects on other neurotransmission systems, including the serotonin (5-hydroxytryptamine, 5-HT) system. Signalling between oxytocin (OT) and 5-HT has been demonstrated during neurodevelopment and in the regulation of specific emotion-based behaviours. It is suggested that crosstalk between neurotransmitters is driven by interaction between their specific receptors, particularly the oxytocin receptor (OTR) and the 5-hydroxytryptamine 2C receptor (5-HTR2C), but evidence for this and the downstream signalling consequences that follow are lacking. Considering the overlapping central expression profiles and shared involvement of OTR and 5-HTR2C in certain endocrine functions and behaviours, including eating behaviour, social interaction and locomotor activity, we investigated the existence of functionally active OTR/5-HTR2C heterocomplexes. Here, we demonstrate evidence for a potential physical interaction between OTR and 5-HTR2C in vitro in a cellular expression system using flow cytometry-based FRET (fcFRET). We could recapitulate this finding under endogenous expression levels of both receptors via in silico analysis of single cell transcriptomic data and ex vivo proximity ligation assay (PLA). Next, we show that co-expression of the OTR/5-HTR2C pair resulted in a significant depletion of OTR-mediated G alpha q-signalling and significant changes in receptor trafficking. Of note, attenuation of OTR-mediated downstream signalling was restored following pharmacological blockade of the 5-HTR2C. Finally, we demonstrated a functional relevance of this novel heterocomplex, in vivo, as 5-HTR2C antagonism increased OT-mediated hypoactivity in mice. Overall, we provide compelling evidence for the formation of functionally active OTR/5-HTR2C heterocomplexes, adding another level of complexity to OTR and 5-HTR2C signalling functionality.This article is part of the special issue on Neuropeptides.