Recent studies suggest that certain aspects of depression, anxiety and vulnerability to stress could result from exposure to harmful environmental conditions or early adverse experiences capable of disturbing different neurotransmission systems during individuals’ childhood . Now, a study by a CONICET research group managed to describe in a mouse model a biological mechanism whose alteration would increase the vulnerability to developing certain psychiatric diseases in adulthood. The work was published in the journal Development.
“Knowing the early brain mechanisms that predispose us to developing depression, anxiety and greater vulnerability to stress could serve to search for psychotropic drugs that correct functional changes in neuronal circuits, and thus improve the therapeutic approach to these psychiatric disorders,” says Mariano . Soiza Reilly , doctor in Biology from the UBA, leader of the study and CONICET researcher at the Institute of Physiology, Molecular Biology and Neurosciences (IFIBYNE, CONICET-UBA).
serotonin neurons
In depression and anxiety , alterations are recorded in the levels of serotonin , a neurotransmitter that is synthesized in the brain in the raphe nuclei , a region whose activity regulates emotions, responses to stress, breathing, locomotion, and appetite. and other functions.
Although there are several studies on the maturation of serotonin neurons in the dorsal raphe nucleus, very little is known about how connections between these neurons and the prefrontal cortex are established and refined during postnatal development. “This brain circuit is of great interest since it controls individuals’ responses to stressful situations. Preclinical studies in rodents reveal that the alteration of this connection, as a result of adverse experiences during postnatal development, predisposes animals to develop depressive and anxious behaviors in adulthood,” says Soiza Reilly.
In the recent work, Soiza Reilly and her team managed to describe for the first time the trajectory of neural circuits that come from different regions of the brain, including the prefrontal cortex, and how they connect with the raphe nucleus. “We studied the development of the mouse brain and were able to verify that between the third and fourth postnatal weeks the neurons of the prefrontal cortex mature their connections with the neurons of the raphe nucleus,” highlights the CONICET researcher.
In addition to electrophysiological analyzes carried out by Paula Perissinotti , PhD in Biology and CONICET researcher at the same institute, the team used a novel high-resolution microscopy technique called array tomography based on “ultrathin slice” immunofluorescence that Soiza Reilly developed during her postdocs at the Boston Children’s Hospital associated with Harvard University, in the United States, and at the French National Institute of Health and Medical Research (INSERM) and at the Sorbonne University, in Paris, France. With this technique, the CONICET specialists obtained three-dimensional images that made it possible to evaluate with high precision the different stages of the maturation of the study circuit.
“Based on these results, we propose to explore therapeutic strategies in preclinical models that can ’correct’ these alterations in maturation and check whether the pathophysiological symptoms can be prevented or improved,” says Soiza Reilly. And she adds: “The results of these studies could shed light on how modifications in the formation and maturation of brain circuits during different stages of neurodevelopment can contribute to the etiology of psychiatric diseases.”
The first authors of the work are Carla Argañaraz and Tamara Adjimann, biologists from the UBA and doctoral fellows from CONICET at IFIBYNE.
