The role of oxytocin in heart failure-induced cognitive and mood disorders
Molecular and Cellular Neurology and Neuropathology
Final Report Abstract
The main aim of this funded project was the investigate the role of the neuropeptide oxytocin in mood and cognitive disorders in a rat model of heart failure. Our hypothesis was that oxytocin signaling in a particular brain region, the central amygdala, is impaired in heart failure. This brain region is involved in fear learning and emotional memory and oxytocin release within this brain region relieves anxiety and promotes comfort. While we obtained several interesting findings, many of the proposed experiments could not be performed, because of problems with our viral vectors. These viruses are used to produce specific proteins in cells, which help us to determine the precise role of these cells during a specific experiment. During my Fellowship, I contributed to a list of other projects, which have now been published in Nature Neuroscience (2x), Journal of Neuroinflammation and Cell Reports. We obtained novel and surprising data on different topics, which are listed below: • We developed a new surgery technique that allows us to access the ventral surface (bottom) of the brain. This is particularly interesting, as we can now study brain regions that are located deep inside the brain and that were previously inaccessible. With this new technique we made an astonishing finding about the interaction of blood flow and neuronal activity during salt intake. We found that in a specific subset of neurons, so called vasopressin neurons, the so-called neurovascular coupling, the link between blood supply and cellular activity, is essentially reversed compared to what has been reported before in other brain regions. • We found that a specific type of glial, astrocytes, responds to the neuropeptide oxytocin. This is very intriguing, as the literature only described activation of neurons, but not astrocytes, by oxytocin. We report that these astrocytes are critical for brain function and are involved in the emotional regulation of rats and mice during a behavioral task. • We achieved the first-ever electrical recording of oxytocin cells in alive, freely moving female rats during social interaction. We used so called optotetrodes to record electrical activity in brain cells during social interaction and found that oxytocin neurons are active when rats are sniffing and touching each other. When we artificially silenced these cells, we observed a significant reduction in social interaction, thus highlighting their importance. • We developed a new technique to track, model and analyze cellular morphology using a software for three-dimensional reconstruction. We applied this technique to microglia, which are the immune cells of the brain. In our rat model of heart failure, we observed that microglia display a changed cellular morphology, which was indicative of an inflammation in the brain. This was supported by elevated levels of markers for neuroinflammation.
Publications
- (2020). Social touch promotes inter-female communication via oxytocin parvocellular neurons. Nature Neuroscience
Tang, Y., Benusiglio, D., Lefevre, A., Hilfiger, L., Althammer, F., Bludau, A., Hagiwara, D., Baudon, A., Schimmer, J., Kirchner, M.K., et al.
(See online at https://doi.org/10.1038/s41593-020-0674-y) - (2020). Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats. J Neuroinflammation 17, 221
Althammer, F., Ferreira-Neto, H.C., Rubaharan, M., Roy, R.K., Patel, A.A., Murphy, A., Cox, D.N., and Stern, J.E.
(See online at https://doi.org/10.1186/s12974-020-01892-4) - (2021). Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents. Nature Neuroscience (Apr;24(4):529-541
Wahis, J., Kerspern, D., Althammer, F., Baudon, A., Goyon, S., Hagiwara, D., Lefèvre, A., Boury-Jamot, B., Bellanger, B., Abatis, M., et al.
(See online at https://doi.org/10.1038/s41593-021-00800-0) - 2021. 'Inverse neurovascular coupling contributes to positive feedback excitation of vasopressin neurons during a systemic homeostatic challenge', Cell Rep, 37: 109925
Roy, R. K., F. Althammer, A. J. Seymour, W. Du, V. C. Biancardi, J. P. Hamm, J. A. Filosa, C. H. Brown, and J. E. Stern
(See online at https://doi.org/10.1016/j.celrep.2021.109925) - Central and peripheral release of oxytocin: relevance of neuroendocrine and neurotransmitter actions for physiology and behavior. The Human Hypothalamus, Editor Dick Swaab (2021 Handb Clin Neurol. 2021;180:25-44
Ferdinand Althammer, Marina Eliava and Valery Grinevich
(See online at https://doi.org/10.1016/b978-0-12-820107-7.00003-3) - The Multifaceted Roles of Hypothalamic Astrocytes and Microglial Cells in Neuroendocrine and Autonomic Regulation in Health and Disease. Masterclass in Neuroendocrinology (2021)
Ferdinand Althammer and Javier Stern
(See online at https://doi.org/10.1007/978-3-030-62383-8_5)
