Abstract
The sharing of circulation between two animals using a surgical procedure known as parabiosis has created a wealth of information towards our understanding of physiology, most recently in the neuroscience arena. The systemic milieu is a complex reservoir of tissues, immune cells, and circulating molecules that is surprisingly not well understood in terms of its communication across organ systems. While the model has been used to probe complex physiological questions for many years, critical parameters of recovery and exchange kinetics remain incompletely characterized, limiting the ability to design experiments and interpret results for complex questions. Here we provide evidence that mice joined by parabiosis gradually recover much physiology relevant to the study of brain function. Specifically, we describe the timecourse for a variety of recovery parameters, including those for general health and metabolism, motor coordination, activity, and sleep behavior. Finally, we describe the kinetics of chimerism for several lymphocyte populations as well as the uptake of small molecules into the brains of mice following parabiosis. Our characterization provides an important resource to those attempting to understand the complex interplay between the immune system and the brain as well as other organ systems.
Highlights
Decrease in blood have been controversial, future studies will clarify the role of Growth and differentiation factor 11 (GDF11) in aged tissues, its reliable detection, and the conditions under which it exerts its effects
Heterochronic parabiosis was instrumental in identifying pro-aging factors that stifle adult neurogenesis, including CCL1120 and β2-microglobulin[26] (β2M)
We provide the first description of recovery parameters for the parabiosis model, which will serve as a resource to design experiments that assess complex interactions between the systemic and CNS compartments or other organ systems
Summary
Decrease in blood have been controversial (see Hinken et al.[23], Walker et al.[24], Conboy et al.[25] for recent work or reviews), future studies will clarify the role of GDF11 in aged tissues, its reliable detection, and the conditions under which it exerts its effects. Heterochronic parabiosis was instrumental in identifying pro-aging factors that stifle adult neurogenesis, including CCL1120 and β2-microglobulin[26] (β2M). The modern procedure is inspired by earlier versions of the surgical procedure but with adaptations that increase survival and recovery, including enhanced post-operative monitoring, the use of animals of the same genetic background, and suturing the joints together to promote coordinated movement. Despite these improvements, many questions still remain regarding recovery of the animals following parabiosis, hampering acceptance and implementation of the model as well as the design and interpretation of experiments. We provide the first description of recovery parameters for the parabiosis model, which will serve as a resource to design experiments that assess complex interactions between the systemic and CNS compartments or other organ systems
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