Final Report Summary - NEUREN (NEUREN - Neuroscience Research Exchange Network (NEUREN)) The activities relied on the mobilities that are funded by the NEUREN grants, and they deepen the euro-Mediterranean collaborations and partnership that have been initiated within the framework of the NEUREN project. All workpackages comprised collaborative aspects between European and Mediterranean South countries, and, when relevant, between European and third-partner industrialized countries.The activities performed increased the scientific knowledge in various fields of Neuroscience. Namely, the NEUREN project allowed progress in :WP1. The mechanisms of pain transmission in the spinal cord, and the role that descending control can play in the inhibition of pain information transfer. We confirmed the role of peptidergic system in the modulation of descending controls to the spinal cord and in the inhibition of nociceptive information at the spinal level. Our data also point to a specific role of growth factors (BDNF and GDNF), and oxidative stress mechanisms. Finally, miRNAs appear as master switches of pain processes at the level of the spinal cord.WP2. The role of neurodevelopmental mechanisms and neurogenesis in the onset of psychiatric disorders, e.g. autism and schizophrenia.Neurodevelopmental processes are of importance in the development of psychiatric disorders. We assessed the role of medio-dorsal afferents during development on the morphological and functional maturation of the prefrontal cortex and the basolateral amygdala. Our conclusion is that alterations of this system are involved in cognitive symptoms associated with schizophrenia. In a second set of experiments, we have demonstrated that the ligand neuregulin1 (NRG1) and its receptor ErbB4, genes conferring susceptibility to schizophrenia, also play a key role in the control of neuronal migration. Finally, we demonstrated that prenatally exposure to paint thinner causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice. This shows the risk that mothers who abuse thinner paint expose their offspring.WP3. The roles of specific peptidergic systems, e.g.the nucleus incertus/relaxin-3/RXFP3 system, in the control of cognitive and emotional processing and their potential therapeutic efficacy in the treatment of neurological and mental disorders.We have studied in depth the role of the relaxin-3/RXFP3 peptidergic system in the control of cognitive and emotional processes by providing novel anatomical insights on the connectivity involving this peptidergic system. In addition, we demonstrated that the relaxin-3/RXFP3 system control the paraventricular neurons, and hence the orexine neurons, therefore playing a role in food intake. WP4. The mechanisms of learning and motivation in animal models and humans. This WP deals studies cognitive functions and particularly the mechanisms of learning. In addition, it aims at determining how neurological disorders, such as epilepsy, can alter learning processes. The results obtained are two folds. We first demonstrated that dopamine is not necessary for learning in animal but rather for engaging the effort required to learn. In a second set of experiments, we showed that the extract of Anacyclus pyrethrum has strong beneficial effects on epileptic rats, suggesting that it may be used as a safe and effective natural substance to ameliorate seizure severity and to protect against oxidative stress provoked by epilepsy.WP5. The mechanisms that underly, and the possible treatments that can antagonize, the onset and maintenance of post-traumatic stress disorder, an emotionally debilitating mental illness that may develop after exposure to a traumatic event.The study proposed here aimed to examine mechanisms of post-traumatic stress disorder (PTSD) relapse. Our data indicate that prevention of PTSD relapse is specific to post-treatment prefrontal hyperactivation. In addition, during PTSD remission, maintenance of PTSD comorbid psychiatric disorders, such as trait anxiety and substance use disorder (SUD) that are specifically characterized by dysfunctional prefrontal cortex, contribute to PTSD relapse.WP6. The improvement of spine MRI practice with a special emphasis on paraspinal analysis of soft tissue.
