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Witztum, R.

Publications and source records attributed to Witztum, R..

2 recordsLinked to original sources

Single Transcript Level Atlas of Oxytocin and the Oxytocin Receptor in the Mouse Brain

Oxytocin (OXT), a primitive nonapeptide known to regulate reproduction and social behaviors, is synthesized primarily in the hypothalamus and is secreted via hypophyseal-portal system of the posterior pituitary gland. Given that pituitary hormones, traditionally thought of as regulators of single targets, display an array of central and peripheral actions, OXT also directly affects bone and body composition. Its effects on bone remodeling are physiologically relevant, as elevated OXT levels during pregnancy and lactation could cause calcium mobilization from the maternal skeleton for intergenerational calcium transfer towards fetal bone growth. 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, can be exerted. To purposefully address the effects of OXT on the brain, we used RNAscope to map OXT and OXTR expression, at the single transcript level, in the whole mouse brain. Identification of brain nuclei with the highest OXT and OXTR transcript density will shed further light on functional OXT nodes that could be further interrogated experimentally to define new physiologic circuitry.

physiology↗

An Atlas of Brain-Bone Sympathetic Neural Circuits

There is clear evidence that the sympathetic nervous system (SNS) mediates bone metabolism. Histological studies show abundant SNS innervation of the periosteum and bone marrow--these nerves consist of noradrenergic fibers that immunostain for tyrosine hydroxylase, dopamine beta hydroxylase, or neuropeptide Y. Nonetheless, the brain sites that send efferent SNS outflow to bone have not yet been characterized. Using pseudorabies (PRV) viral transneuronal tracing, we report, for the first time, the identification of central SNS outflow sites that innervate bone. We find that the central SNS outflow to bone originates from 87 brain nuclei, sub-nuclei and regions of six brain divisions, namely the midbrain and pons, hypothalamus, hindbrain medulla, forebrain, cerebral cortex, and thalamus. We also find that certain sites, such as the raphe magnus (RMg) of the medulla and periaqueductal gray (PAG) of the midbrain, display greater degrees of PRV152 infection, suggesting that there is considerable site-specific variation in the levels of central SNS outflow to bone. This comprehensive compendium illustrating the central coding and control of SNS efferent signals to bone should allow for a greater understanding of the neural regulation of bone metabolism, and importantly and of clinical relevance, mechanisms for central bone pain.

neuroscience↗