Oxytocin could promote the growth of new neurons to repair damaged tissue

Learning a new task, mastering a musical instrument or being able to adapt to the constantly changing environment are all possible thanks to the brain’s plasticity, or its ability to modify itself by rearranging existing neural networks and forming new ones to acquire new functional properties. This also helps neural circuits to remain healthy, robust and stable.

To better understand brain plasticity, a team of researchers at Baylor College of Medicine and Texas Children’ Hospital used mouse models to investigate how brain cells build connections with new neurons born in adult brains.

Their findings, published in the journal Genes & Development, not only expand our understanding of brain plasticity but also open new possibilities for treating certain neurodevelopmental disorders and repairing injured circuits in the future.

“In this study, we wanted to identify new molecules that help new neurons build connections in the brain,” said corresponding author Dr. Benjamin R. Arenkiel, professor of molecular and human genetics and neuroscience at Baylor and the Duncan Neurological Research Institute at Texas Children’s.

“We worked with the olfactory bulb, the part of the brain that is involved in the sense of smell. In mice, the olfactory bulb is a highly plastic sensory area and has a remarkable capacity to maintain plasticity into adulthood via continuous integration of adult-born neurons. We discovered that oxytocin, a peptide, or short protein, produced in the brain, drives events that contribute to neural circuit plasticity.”

The researchers discovered that the levels of oxytocin increase in the olfactory bulb, peaking at the time the new neurons incorporate themselves into neural networks.

Using viral labeling, confocal microscopy and cell-type specific RNA sequencing, the team discovered that oxytocin triggers a signaling pathway—a series of molecular events inside cells—that promotes the maturation of synapses, that is, the connections of newly integrated adult-born neurons. When the researchers eliminated the oxytocin receptor, the cells had underdeveloped synapses and impaired function.

“Importantly, we found that synapse maturation occurs by regulating the morphological development of cells and the expression of a number of structural proteins,” said Arenkiel, a MacNair Scholar at Baylor.

“The most exciting aspect of this study is that our findings suggest that oxytocin drives development and synaptic integration of new neurons within the adult brain, directly contributing to adaptability and circuit plasticity,” said first author Brandon T. Pekarek, a graduate student—research assistant in the Arenkiel lab.

The findings, which are relevant to all mammals, including humans, open new possibilities to improve neurological conditions.

“Oxytocin is normally present in our brain, so if we understand how to turn it on or off or mobilize it, we can help keep our circuit connections healthy by promoting the growth of underdeveloped connections or strengthening new ones,” Arenkiel said.

“Our findings also suggest that oxytocin could promote the growth of new neurons to repair damaged tissue. Further studies are needed to explore these possibilities.”

Oxytocin is a neuropeptide, released both peripherally and centrally, that has been linked to social behaviors such as mating and parenting (Carter et al., 2008; Neumann, 2009; Shelley et al., 2006; Young and Wang, 2004). Oxytocin has also been shown to buffer against some of the negative effects of stress (Cohen et al., 2010; Windle et al., 2004; 2006) – its actions include a reduction in hypothalamic-pituitary adrenal (HPA) axis activity and diminished stress-induced activation of brain regions associated with the HPA axis, including the hippocampus.

Oxytocin enhances hippocampal synaptic plasticity and cognitive functions of mother rats (Tomizawa et al., 2003), but its overall influence on this brain region remains unexplored. The hippocampus is a site of structural plasticity, undergoing neurogenesis throughout life – evidence has linked cognitive, anxiety and stress regulation functions of the hippocampus to adult neurogenesis (Leuner and Gould, 2010). Oxytocin neurons in the hypothalamic paraventricular nucleus project to various brain regions, including the hippocampus (Bujis and Swaab, 1979; Sofroniew, 1983). Oxytocin receptors are present in the hippocampus where they are more concentrated in the ventral than dorsal region and subject to modulation by stress and glucocorticoids (Liberzon and Young, 1997).

Oxytocin has been shown to affect cell proliferation in peripheral systems, exhibiting stimulatory effects on blood cells, osteoblasts and some types of tumor cells (Macciò et al., 2010; Petersson, 2008) as well as inhibitory effects on prostate and mammary cells (Petersson, 2008; Sapino et al., 1998; Whittington et al., 2007), but its ability to influence neuronal growth in the brain remains unexplored. Since stress and glucocorticoids can be potent regulators of cell proliferation and adult neurogenesis in the hippocampus (Leuner et al., 2010; Mirescu and Gould, 2006) and oxytocin is known to attenuate stress responses (Windle et al., 2004; 2006), we investigated whether oxytocin alters adult neurogenesis and whether this effect occurs in the presence of elevated glucocorticoids. Here we show that peripheral and central oxytocin, but not the closely related neuropeptide vasopressin, enhances cell proliferation and adult neurogenesis. The stimulatory effect of oxytocin on cell proliferation occurred even in rats treated with glucocorticoids or exposed to a stressor. These findings raise the possibility that oxytocin acts to protect the hippocampus from the damaging effects of elevated glucocorticoids by promoting neuronal growth.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756590/

Original Research: Closed access.
“Oxytocin signaling is necessary for synaptic maturation of adult-born neurons” by Brandon T. Pekarek et al. Genes & Development