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Marina di Pisa, Italy

Benyamina A.,French Institute of Health and Medical Research | Naassila M.,French Institute of Health and Medical Research | Bourin M.,Neurobiology
Psychiatry Research | Year: 2012

The antipsychotic cyamemazine is a potent serotonin 5-HT2A receptor (5-HT2AR) antagonist. A positron emission tomography (PET) study in human patients showed that therapeutic doses of cyamemazine produced near saturation of 5-HT2AR occupancy in the frontal cortex, whereas dopamine D2 occupancy remained below the level for motor side effects observed with typical antipsychotics. Recently, numerous studies have revealed the involvement of 5-HT2AR in the pathophysiology of anxiety and a double-blind, randomized clinical trial showed similar efficacy of cyamemazine and bromazepam in reducing the anxiety associated with benzodiazepine withdrawal. Therefore, we reviewed the above articles about 5-HT2AR and anxiety in order to understand better the anxiolytic mechanisms of cyamemazine in benzodiazepine withdrawal. The 5-HT2AR is the most abundant serotonin receptor subtype in the cortex. Non-pharmacological studies with antisense oligodeoxynucleotides and genetically modified mice clearly showed that cortical 5-HT2AR signaling positively modulates anxiety-like behavior. With a few exceptions, most other studies reviewed here further support this view. Therefore, the anxiolytic efficacy of cyamemazine in benzodiazepine withdrawal can be due to a 5-HT2AR antagonistic activity at the cortical level. © 2012 Elsevier Ltd.

Mondal S.,Neurobiology
Journal of visualized experiments : JoVE | Year: 2012

Micro fabricated fluidic devices provide an accessible micro-environment for in vivo studies on small organisms. Simple fabrication processes are available for microfluidic devices using soft lithography techniques. Microfluidic devices have been used for sub-cellular imaging, in vivo laser microsurgery and cellular imaging. In vivo imaging requires immobilization of organisms. This has been achieved using suction, tapered channels, deformable membranes, suction with additional cooling anesthetic gas, temperature sensitive gels, cyanoacrylate glue and anesthetics such as levamisole. Commonly used anesthetics influence synaptic transmission and are known to have detrimental effects on sub-cellular neuronal transport. In this study we demonstrate a membrane based poly-dimethyl-siloxane (PDMS) device that allows anesthetic free immobilization of intact genetic model organisms such as Caenorhabditis elegans (C. elegans), Drosophila larvae and zebrafish larvae. These model organisms are suitable for in vivo studies in microfluidic devices because of their small diameters and optically transparent or translucent bodies. Body diameters range from -10 μm to -800 μm for early larval stages of C. elegans and zebrafish larvae and require microfluidic devices of different sizes to achieve complete immobilization for high resolution time-lapse imaging. These organisms are immobilized using pressure applied by compressed nitrogen gas through a liquid column and imaged using an inverted microscope. Animals released from the trap return to normal locomotion within 10 min. We demonstrate four applications of time-lapse imaging in C. elegans namely, imaging mitochondrial transport in neurons, pre-synaptic vesicle transport in a transport-defective mutant, glutamate receptor transport and Q neuroblast cell division. Data obtained from such movies show that microfluidic immobilization is a useful and accurate means of acquiring in vivo data of cellular and sub-cellular events when compared to anesthetized animals (Figure 1J and 3C-F). Device dimensions were altered to allow time-lapse imaging of different stages of C. elegans, first instar Drosophila larvae and zebrafish larvae. Transport of vesicles marked with synaptotagmin tagged with GFP (syt.eGFP) in sensory neurons shows directed motion of synaptic vesicle markers expressed in cholinergic sensory neurons in intact first instar Drosophila larvae. A similar device has been used to carry out time-lapse imaging of heartbeat in -30 hr post fertilization (hpf) zebrafish larvae. These data show that the simple devices we have developed can be applied to a variety of model systems to study several cell biological and developmental phenomena in vivo.

Nyman A.,Lulea University of Technology | Josephsson S.,Neurobiology | Isaksson G.,Lulea University of Technology
Scandinavian Journal of Occupational Therapy | Year: 2014

Aim: The aim of this study was to explore and enhance the understanding of how togetherness in everyday occupations is experienced and discussed among older adults. Method: Focus-group discussions generated the data and a total of 12 participants, including six women and six men, divided into three groups, participated in this study. Analysis was performed using a grounded theory approach. Results: The findings reflect how togetherness in everyday occupations can be comprehended as multifold transactional processes, emphasizing how an acted belonging was a situated experience connecting people and places through unfolding stories. The findings suggest that the process of meaning-making in ongoing life was closely associated with togetherness and was negotiated with others through shared culture and experiences. Togetherness meant being part of something in which the persons involved were contributing to each other in various ways. However, being part of togetherness was complicated, especially when the person's life situation was challenged in some way. Conclusions: It was apparent from the analysis that togetherness could not be taken for granted. Rather, the findings reflect how togetherness was created and maintained through an ongoing process of nurturing established relationships as well as creating something new around occupations with others. © 2014 Informa Healthcare.

Herring B.E.,Neurobiology | McMillan K.,Neurobiology | Pike C.M.,Neurobiology | Marks J.,Pediatrics | And 2 more authors.
Journal of Physiology | Year: 2011

The mechanism of general anaesthetic action is only partially understood. Facilitation of inhibitory GABA A receptors plays an important role in the action of most anaesthetics, but is thought to be especially relevant in the case of intravenous anaesthetics, like etomidate and propofol. Recent evidence suggests that anaesthetics also inhibit excitatory synaptic transmission via a presynaptic mechanism(s), but it has been difficult to determine whether these agents act on the neurotransmitter release machinery itself. In the present study we sought to determine whether the intravenous anaesthetics propofol and etomidate inhibit the release machinery. For these studies we used an experimental approach that directly regulated [Ca 2+] i at neurotransmitter release sites, thereby bypassing anaesthetic effects on channels and receptors in order to allow anaesthetic effects on the neurotransmitter release machinery to be examined in isolation. The data show that clinically relevant concentrations of propofol and etomidate inhibited the neurotransmitter release machinery in neurosecretory cells and in cultured hippocampal neurons. md130A is a mutant form of syntaxin with a truncated C-terminus. Overexpressing md130A in PC12 cells completely eliminated the reduction in neurotransmitter release produced by propofol, without affecting release itself. In contrast, overexpressing md130A in PC12 cells had little or no effect on the response to etomidate. These results suggest that both propofol and etomidate inhibit neurotransmitter release by a direct interaction with SNAREs and/or SNARE-associated proteins but they do so at different sites. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.

Rossi A.,Neurobiology | Calabrese R.,University of Pisa | Consoli G.,Neurobiology | Ciapparelli A.,Neurobiology | Dell'Osso L.,Neurobiology
Clinical and Experimental Rheumatology | Year: 2010

Objectives. To evaluate the role of spasmophilia (SP) in fibromyalgia syndrome (FM). Methods. Three hundred and fourteen patients (280 F, 34 M) with a diagnosis of FM or FM and spasmophilia (FM+SP) were recruited. Clinical assessment of patients and controls included the Questionnaires FIQ, HAQ and the tender point (TP) count. Lifetime or ongoing psychiatric aspects were evaluated by trained psychiatrists by means of the classic scales: Structured Clinical Interview (SCID) for DSM-IV. The following analysis were evaluated: cytokine (ILl, IL2, IL6,1L8, IL10), TNF-α, Cortisol, GH, ACTH, IGF1, 5HT, intracellular Mg, plasma calcium p(Ca), PTH, (25(OH)D) and thyroid functionality. Some typical symptoms were investigated. Results. Eighty-one patients resulted positive for spamophilia (FM+SP), while 233 resulted negative for spasmophilia (FM). The mean TP number resulted higher in the FM group (15.33±3.88) with respect to FM+SP (12.88±6.17, p=0.016), while FIQ and HAQ did not differ between the two studied groups. FM patients exhibited a higher frequency of psychiatric disorders with respect to FM+SP patients (72% FM vs. 49% FM+SP, p<0.01).particular the frequency of depression was 65.5% FM vs. 35% FM+SP (p<0.01). Conclusions. The presence of spasmophilia seems to influence psychiatric comorbidity which was less prevalent in FM+SP patients. FM is indeed characterised by an abnormal sensory processing of pain that seems to result from a combination of interactions between neurotransmitters, stress, hormones and the nervous system; spasmophilia would seem to be more linked to a dysfunction at the neuromuscular level. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2010.

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