Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety.

Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicits anxiety-like behavior and dendritic remodeling in the amygdala. Members of the miR-34 family have been suggested to regulate synaptic plasticity and neurotransmission processes, which mediate stress-related disorders. Using mice that harbored targeted deletions of all 3 members of the miR-34-family (miR-34-TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic and medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo microdialysis. Moreover, we also examined fear conditioning/extinction, stress-induced anxiety, and dendritic remodeling in the BLA of stress-exposed TKO mice. We found that TKO mice showed resilience to stress-induced anxiety and facilitation in fear extinction. Accordingly, no significant increase was evident in aminergic prefrontal or amygdala GABA release, and no significant acute stress-induced amygdalar dendritic remodeling was observed in TKO mice. Differential GRM7, 5-HT2C, and CRFR1 mRNA expression was noted in the mpFC and BLA between TKO and WT mice. Our data demonstrate that the miR-34 has a critical function in regulating the behavioral and neurochemical response to acute stress and in inducing stress-related amygdala neuroplasticity.

The role of narrative medicine in pregnancy after liver transplantation.

UNLABELLED: Narrative medicine allows professionals from all fields of medical sciences to understand the patient's total experience of illness, and meet his/her needs in an empathetic environment. Narrative medicine helps spread holistic knowledge of a multitude of complex clinical conditions, including transplantation. OBJECTIVE: To underline the role of narrative medicine in women who become pregnant after a liver transplant by using their narrations of this very special experience. METHODS: We describe our study with narration and listening to the stories of three women expecting their first child after a liver transplant, by analysing the structure and role of narration in the context of relationships between patients and caregivers. The narrations were transcribed verbatim with the main plot analysed in order to address all the aspects of this rare clinical condition and the transition to parenthood. RESULTS: The women narrated this experience in three phases: transplantation, pregnancy and delivery, and post-partum. They described all phases of pregnancy as stressful but satisfying, whereas the fact of becoming a mother was perceived as a victory both as a woman and as a transplant patient. CONCLUSIONS: Our results suggest that narrative medicine represents a significant professional tool for caring for transplant patients during pregnancy.

Fear but not fright: re-evaluating traumatic experience attenuates anxiety-like behaviors after fear conditioning.

Fear allows organisms to cope with dangerous situations and remembering these situations has an adaptive role preserving individuals from injury and death. However, recalling traumatic memories can induce re-experiencing the trauma, thus resulting in a maladaptive fear. A failure to properly regulate fear responses has been associated with anxiety disorders, like Posttraumatic Stress Disorder (PTSD). Thus, re-establishing the capability to regulate fear has an important role for its adaptive and clinical relevance. Strategies aimed at erasing fear memories have been proposed, although there are limits about their efficiency in treating anxiety disorders. To re-establish fear regulation, here we propose a new approach, based on the re-evaluation of the aversive value of traumatic experience. Mice were submitted to a contextual-fear-conditioning paradigm in which a neutral context was paired with an intense electric footshock. Three weeks after acquisition, conditioned mice were treated with a less intense footshock (pain threshold). The effectiveness of this procedure in reducing fear expression was assessed in terms of behavioral outcomes related to PTSD (e.g., hyper-reactivity to a neutral tone, anxiety levels in a plus maze task, social avoidance, and learning deficits in a spatial water maze) and of amygdala activity by evaluating c-fos expression. Furthermore, a possible role of lateral orbitofrontal cortex (lOFC) in mediating the behavioral effects induced by the re-evaluation procedure was investigated. We observed that this treatment: (i) significantly mitigates the abnormal behavioral outcomes induced by trauma; (ii) persistently attenuates fear expression without erasing contextual memory; (iii) prevents fear reinstatement; (iv) reduces amygdala activity; and (v) requires an intact lOFC to be effective. These results suggest that an effective strategy to treat pathological anxiety should address cognitive re-evaluation of the traumatic experience mediated by lOFC.

Tis21 is required for adult neurogenesis in the subventricular zone and for olfactory behavior regulating cyclins, BMP4, Hes1/5 and Ids.

Bone morphogenic proteins (BMPs) and the Notch pathway regulate quiescence and self-renewal of stem cells of the subventricular zone (SVZ), an adult neurogenic niche. Here we analyze the role at the intersection of these pathways of Tis21 (Btg2/PC3), a gene regulating proliferation and differentiation of adult SVZ stem and progenitor cells. In Tis21-null SVZ and cultured neurospheres, we observed a strong decrease in the expression of BMP4 and its effectors Smad1/8, while the Notch anti-neural mediators Hes1/5 and the basic helix-loop-helix (bHLH) inhibitors Id1-3 increased. Consistently, expression of the proneural bHLH gene NeuroD1 decreased. Moreover, cyclins D1/2, A2, and E were strongly up-regulated. Thus, in the SVZ Tis21 activates the BMP pathway and inhibits the Notch pathway and the cell cycle. Correspondingly, the Tis21-null SVZ stem cells greatly increased; nonetheless, the proliferating neuroblasts diminished, whereas the post-mitotic neuroblasts paradoxically accumulated in SVZ, failing to migrate along the rostral migratory stream to the olfactory bulb. The ability, however, of neuroblasts to migrate from SVZ explants was not affected, suggesting that Tis21-null neuroblasts do not migrate to the olfactory bulb because of a defect in terminal differentiation. Notably, BMP4 addition or Id3 silencing rescued the defective differentiation observed in Tis21-null neurospheres, indicating that they mediate the Tis21 pro-differentiative action. The reduced number of granule neurons in the Tis21-null olfactory bulb led to a defect in olfactory detection threshold, without effect on olfactory memory, also suggesting that within olfactory circuits new granule neurons play a primary role in odor sensitivity rather than in memory.

[Living donor kidney transplant: the vision of the Italian National Transplant Center]. / Trapianto di rene da donatore vivente: la visione del CNT.

Living donor kidney transplantation offers an additional opportunity for patients with renal failure. The Italian National Transplant Center has collected data on kidney transplants from living donors since 2001. The data revealed a sharp increase in recent years, although the number of living donor transplants is still low compared to the number of patients on the waiting list. The National Transplant Center aims to promote the opportunity for kidney transplants from living donors and to provide information to all stakeholders, including information on specific programs such as crossover transplantation and Samaritan donation. The ultimate purpose of the National Transplant Center is to reduce the waiting lists for kidney transplants in Italy.

TRAIN: Training through Research Application Italian iNitiative.

Training through Research Application Italian iNitiative (TRAIN) is a mobility program financed under the EU action called "Cofinancing of regional, national and international programs" (COFUND) of the European Commission Seventh Framework Program (FP7) - People, and has been designed to encourage the promotion and development of international programs of research through mobility at various stages of research careers. The aim of TRAIN is to improve translational skills in the field of cancer by promoting a three-year international mobility program assigning a total of 51 fellowships subdivided into incoming, outgoing and reintegration fellowships.?The TRAIN proposal has been submitted in February 2009 to the European Commission in reply to the 2008 FP7-PEOPLE-COFUND call and has been successfully evaluated. TRAIN is addressed to postdoctoral scientists or scientists who have at least four years' full-time equivalent research experience and who wish to improve their careers spending one year abroad. The mobility program is open also to non-Italian experienced scientists wishing to spend one year in an Italian research center or private company. Part of the scheme is targeted to experienced Italian scientists who have completed at least three years of research in a foreign country and are interested in returning to Italy.?TRAIN is part of an overall Italian strategy outlined by the International Program of the Italian Cancer Network "Alleanza Contro il Cancro" to promote Italian participation in the building of the European Area for translational cancer research and to enhance the interaction between academy and industry.

Training and mobility: a priority for the Organisation of the European Cancer Institutes. How a national mobility initiative could enhance EU cooperation in cancer research contributing to the development of an European Research Area: the example of The Italian Comprehensive Cancer Centers' Network "Alleanza Contro il Cancro".

It is widely recognized that productivity gains, sustained economic growth and employment are largely determined by technological progress, innovation and human capital. The 2000 Lisbon strategy to make Europe a competitive knowledge-based economy by 2010 and, more specifically, the Barcelona objectives agreed upon in 2002 to increase R&D investment in the EU to approach 3% of GDP, ensuring that there are sufficient human resources for research, are a preliminary step in this direction. If we want to reach this goal we have to succeed in retaining the best researchers, creating the right environment where they can perform their activities and develop their careers. To this aim the Organization of European Cancer Institutes (OECI) has set up a working group on Education and Training with the mandate to encourage continuing education in cancer research and applications and to verify the feasibility to promote mobility programs inside the network and in association with industries. Until now only few OECI training programs have been launched and a full mobility program has not been developed yet due to limited budget resources. The Italian Network of Comprehensive Cancer Centers, Alleanza Contro il Cancro, has planned the launch of a mobility program awarding 70 annual fellowships over a period of 36 months. This program, which will be open to the world research community, could represent a first interaction through mobility among the members of the OECI network also involving industries. The program is a tangible approach to sustain the translational process needed for the development of an European Research Area in the field of cancer and its related biomedical disciplines, thus providing a practical answer to the 2005 renewed Lisbon Strategy.