Project 461071

Mitochondria are small organelles within cells that generate almost all the energy we need throughout life. The human brain, being the most energy-demanding organ, consumes between 50% (in postnatal age) and 20% (in adulthood) of this energy. In fact, there are around 2 million mitochondria per neural cell to orchestrate brain functions. This makes mitochondria critical for cell function, but also a potential major source of problems. Remarkably, it has recently been proposed that mitochondria, beyond "simply" producing energy, have the property of detecting, integrating, and signaling information from the nervous system (such as mood and stress) and the hormonal system (i.e., induced by physiological stress or disease). In fact, the mitochondrion is a platform for the regulation of oxidative stress, cellular metabolism, inflammatory response and release of chemical messengers in the brain. These findings are very relevant because they reveal that mitochondria may be the link in the process that transforms cellular deficiencies into disease. As such, this discovery represents a revolution in our understanding of brain development, function, and disease. In our work (in rodents) we have shown that the stress experienced in the first years of age (such as that induced in cases of maternal depression or conditions that interfere with mother-child interactions), leads to the development of respiratory pathologies in adulthood, which are more frequent in men than in women. All these findings, lead us to propose the hypothesis that stress at an early age leads (in men, not in women) to long-term alteration of mitochondrial functions that ultimately reconfigure cellular metabolism, immune response and synaptic neurotransmission in neural centers involved in respiratory control. This project may open new avenues for the pharmacological treatment of respiratory dysfunction in adulthood in men, and will shed light on why women are better protected.