Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy; Corresponding author
Alessandro Mormino
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Letizia Mazzarella
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Germana Cocozza
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Arianna Rinaldi
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Erika Di Pietro
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Maria Amalia Di Castro
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Eleonora De Felice
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Laura Maggi
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Giuseppina Chece
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Diego Andolina
Department of Psychology and Center for Research in Neurobiology ‘D. Bovet’, Sapienza University of Rome, Rome, Italy
Rossella Ventura
Department of Psychology and Center for Research in Neurobiology ‘D. Bovet’, Sapienza University of Rome, Rome, Italy
Donald Ielpo
Department of Psychology and Center for Research in Neurobiology ‘D. Bovet’, Sapienza University of Rome, Rome, Italy
Roberto Piacentini
Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy; IRCCS Fondazione Policlinico Universitario A. Gemelli, Largo A. Gemelli 1, Roma, Italy
Myriam Catalano
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Lucia Stefanini
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
Cristina Limatola
Laboratory affiliated with Istituto Pasteur, Department of Physiology and Pharmacology, Sapienza University, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy; Corresponding author
Summary: Several lines of evidence have shown that platelet-derived factors are key molecules in brain-body communication in pathological conditions. Here, we identify platelets as key actors in the modulation of fear behaviors in mice through the control of inhibitory neurotransmission and plasticity in the hippocampus. Interfering with platelet number or activation reduces hippocampal serotonin (5-HT) and modulates fear learning and memory in mice, and this effect is reversed by serotonin replacement by serotonin precursor (5-HTP)/benserazide. In addition, we unravel that natural killer (NK) cells participate in this mechanism, regulating interleukin-13 (IL-13) levels in the gut, with effects on serotonin production by enterochromaffin cells and uptake by platelets. Both NK cells and platelet depletion reduce the activation of hippocampal inhibitory neurons and increase the long-term potentiation of synaptic transmission. Understanding the role of platelets in the modulation of neuro-immune interactions offers additional tools for the definition of the molecular and cellular elements involved in the growing field of brain-body communication.
