Single transcript level atlas of oxytocin and the oxytocin receptor in the mouse brain
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eLife Assessment
This fundamental work substantially advances our understanding of OXT (oxytocin) neurons and OXTR (oxytocin receptor) expressions in mammalian brains using an advanced RNAscope at the single transcript level. The evidence supporting the conclusions is compelling using chromogenic assays and state-of-the-art microscopy. The work will be of broad interest to neuroscientists and endocrinologists.
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Abstract
Oxytocin (OXT), a primitive nonapeptide known to regulate reproduction and social behaviors, is synthesized primarily in the hypothalamus and is secreted via the hypophyseal-portal system of the posterior pituitary gland. In line with the premise that pituitary hormones, traditionally thought of as regulators of single targets, display an array of central and peripheral actions, we found that OXT directly affects bone and body composition. The effect of OXT on bone remodeling is physiologically relevant, as elevated OXT levels during pregnancy and lactation cause calcium mobilization from the maternal skeleton for intergenerational calcium transfer towards fetal bone mineralization. There is an equally large body of evidence that has established the presence of OXT receptors (OXTRs) in the brain through which central functions, such as social bonding, and peripheral functions, such as the regulation of body composition, are exerted. To purposefully address effects of OXT on the brain, we used RNAscope to map OXT and OXTR expression, at the single transcript level, in the whole female and male mouse brains. Identification of brain nuclei with the highest OXT and OXTR transcript density sheds further light on functional OXT nodes that could be further interrogated experimentally to define new physiologic circuitry.
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eLife Assessment
This fundamental work substantially advances our understanding of OXT (oxytocin) neurons and OXTR (oxytocin receptor) expressions in mammalian brains using an advanced RNAscope at the single transcript level. The evidence supporting the conclusions is compelling using chromogenic assays and state-of-the-art microscopy. The work will be of broad interest to neuroscientists and endocrinologists.
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Reviewer #1 (Public Review):
This study by Ryu et al, provides compelling evidence to demonstrate the distributions of Oxt and Oxtr in the murine brain using an advanced RNAscope technique. Detailed information on the distributions was provided, revealing differences in Oxt and Oxtr expressions between males and females. This study will provide a new platform for investigators to study previously unknown roles of brain-region specific Oxt and Oxtr neurons and signaling in animal behaviors and metabolism, and others.
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Reviewer #2 (Public Review):
This an exciting study investigating the role of OXT in central nervous system (CNS) regulation of different behaviors and physiological processes. The study clearly shows the expression level of Oxt and Oxtr in different brain nuclei and regions.
Sex differences in Oxt expression are also well demonstrated.
Extensions of OXT's function in CNS regulation are sufficiently discussed.
Overall, this provides a good direction for further investigate OXT's role in CNS's regulation on different behaviors and physiological processes.
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