Parabiosis

For the Homeland episode of the same name, see Parabiosis (Homeland).

Parabiosis is a laboratory technique used in physiological research, derived from the Greek word meaning "living beside." The technique involves the surgical joining of two living organisms in such a way that they develop a single, shared physiological system. Through this unique approach, researchers can study the exchange of blood, hormones, and other substances between the two organisms, allowing for the examination of a wide range of physiological phenomena and interactions. Parabiosis has been employed in various fields of study, including stem cell research, endocrinology, aging research, and immunology.

Physiology

Parabiotic experiments

Left: A headless Cecropia Moth joined with a pupa of the Polyphemus silkworm. Right: The abdomen of a Cecropia moth joined with a Cecropia pupa

Parabiosis combines two living organisms which are joined surgically and develop single, shared physiological systems.^[1][2] Researchers can prove that the feedback system in one animal is circulated and affects the second animal via blood and plasma exchange.

Parabiotic experiments were pioneered by Paul Bert in the mid-1800s. He postulated that surgically connected animals could share a circulatory system. Bert was awarded the Prize of Experimental Physiology of the French Academy of Science in 1866 for his discoveries.^[3]

One limitation of the experiments is that outbred rats cannot be used because it can lead to a significant loss of pairs due to intoxication of the blood supply from a dissimilar rat.^[4]

Discovery of leptin and the role of the hypothalamus in obesity

Many of the parabiotic experiments since 1950 involve research regarding metabolism. One of these experiments was published in 1959 by G. R. Hervey in the Journal of Physiology. This experiment supported the theory that damage to the hypothalamus, particularly the ventromedial hypothalamus, leads to obesity caused by the overconsumption of food. The study's rats were from the same litter, which had been a closed colony for multiple years. The two rats in each pair had no more than a 3% difference in weight. Rats were paired at four weeks old. Unpaired rats were used as controls. The rats were conjoined in three ways. In early experiments, the peritoneal cavities were opened and connected between the two rats. In later experiments, to avoid the risk of tangling the two rats’ intestines together, smaller cuts were made. After further refinement of the experimental procedure, the abdominal cavities were not opened, and the rats were conjoined at the hip bone with minimal cutting. To prove that the two animals were sharing blood, researchers injected dye into one rat's veins, and the pigment would show up in the conjoined rat.

In each pair, one rat became obese and exhibited hyperphagia. The weight of the rat with the surgical lesion rose rapidly for a few months, then reached a plateau as a direct result of the surgical procedure. After the procedure, the rat with the impaired hypothalamus ate voraciously while the paired rat's appetite decreased. The paired rat became obviously thin throughout the experiment, even rejecting food when it was offered.^[5][6]

Later studies identified this satiety factor as the adipose-derived hormone leptin. Many hormones and metabolites were proven not to be the satiety factor that caused one rat to starve in the experiments. Leptin seemed like a viable candidate. Starting in 1977, Ruth B.S. Harris, a graduate student under Hervey, repeated previous studies about parabiosis in rats and mice. Due to the discovery of leptin, she analyzed leptin concentrations of the mice in the parabiotic experiments. After injecting leptin into each pair's obese mouse, she found that leptin circulated between the conjoined animals, but the circulation of leptin took some time to reach equilibrium. As a result of the injections, the almost immediate weight loss resulted in the parabiotic pairs due to increased inhibition. Approximately 50–70% of fat was lost in pairs. The obese mouse lost only fat. The lean mouse lost muscle mass and fat. Harris concluded that leptin levels are increased in obese animals, but other factors could also affect them. Also, leptin was determined to decrease fat storage in both obese and thin animals.^[4]

Early parabiotic experiments also included cancer research. One study, published in 1966 by Friedell, studied radiation's effects with X-rays on ovarian tumors. To study the tumors, two adult female rats were conjoined. The left rat was shielded, and the right rat was exposed to high levels of radiation. The rats were given a controlled amount of food and water. 149 of 328 pairs showed possible ovarian tumors in the irradiated animals, but not in their partners. This result matched previous studies of single rats.^[7]

Aging research

See also: Young blood transfusion

Chronic diseases of age are studied by conjoining an older animal with a younger animal. Known as heterochronic parabiosis, this process has been used in studies to investigate the age-related and disease-related changes in the composition of the blood, especially plasma proteome.^[8] This process could be used to research cardiovascular disease, diabetes, osteoarthritis, and Alzheimer's disease. As animals age, their oligodendrocytes reduce in efficiency, resulting in decreased myelination, causing negative effects on the central nervous system (CNS). Julia Ruckh and fellow researchers have used parabiosis to study remyelination from adult stem cells to see if conjoining young with older mice could reverse or delay this process. The two mice were conjoined in the experiment, and demyelination was induced via injection into the older mice. The experiment determined that the younger mice's factors reversed CNS demyelination in older mice by revitalizing the oligodendrocytes. The monocytes from the younger mice also enhanced the older mice's ability to clear myelin debris because the young monocytes can clear lipids from myelin sheaths more effectively than older monocytes. The conjoining of the two animals reversed the effects of age on the myelination cells. The ability of the young mouse's cells was unaffected. Enhanced immunity from the younger mouse also promoted the general health of the older mouse in each pair. The results of this experiment could lead to therapy processes for people with demyelinating diseases like multiple sclerosis.^[9][3]

Natural examples

The term is also applicable to spontaneously occurring conditions such as in conjoined twins.^[10]

Obligate parasitic reproduction of Anglerfish of the family Ceratiidae, in which the circulatory systems of the males and females unite completely. Without the attachment of males to females, the endocrine functions cannot mature; the individuals fail to develop properly and die young and without reproducing.^[11]

Plants growing closely together roots or stems in intimate contact sometimes form natural grafts. In parasitic plants such as mistletoe and dodder the haustoria unite the circulatory systems of the host and the parasite so intimately that parasitic twiners such as Cassytha may act as vectors carrying disease organisms from one host plant to another.^[12]

Ecology

Social organisms sharing nests

Crematogaster modiglianii and Camponotus rufifemur ants sharing a nest

Ant colonies can share their nests with essentially unrelated species of ants, and even non-ants. They did not obviously share anything beyond the nests' upkeep, even segregating their brood, so these were very surprising observations; most ants are radically intolerant of intruders, usually including even intruders of their own species.

In the early 20th century Auguste-Henri Forel coined the term "parabiosis" for such associations, and it was adopted by the likes of William Morton Wheeler.^[13][14] Furthermore, there is evidence for the partitioning of functions of work between the two species in the nest.^[15] Early reports that parabiotic ant colonies forage and feed together peacefully also have been qualified by observations that revealed ants of one species in such an association aggressively displacing members of the other species from artificially provided food, while also profiting by following their recruitment trails to new food sources.^[14] Benefits from shared nest defence and maintenance even when there is neither direct cooperation nor interaction between the two associated populations in a nest.^[16]

Etymology

Parabiosis derives most directly from Neo-Latin,^[10] but the Latin in turn derives from two classical Greek roots. The first is παρά (para) for "beside" or "next to". In modern etymology, this root appears in various senses, such as "close to", "outside of", and "different".

• In the physiological sense of "parabiosis," "para" apparently was intended to mean "next to."
• In describing transiently inactive physiological states, "para" apparently meant "outside of."
• In ecological usage, the word was coined by the entomologist Auguste-Henri Forel as an analog to "symbiosis," also in the sense of "next to." However, in this case, the emphasis was in contrast to "together" ("sym-").

The second classical Greek root from which the Latin derives is βίος (bios), meaning "life."

See also

• Commensalism – Beneficial symbiosis between species
• Mutualism (biology) – Mutually beneficial interaction between species
• Symbiosis – Close, long-term biological interaction between distinct organisms (usually species)

References

1. Biju Parekkadan & Martin L. Yarmush (eds). Stem Cell Bioengineering. Chapter 10: "Parabiosis in aging research and regenerative medicine" Artech House 2009 ISBN 978-1596934023
2. Zarrow, M. X. Experimental Endocrinology: A Sourcebook of Basic Techniques Academic Press 1964 ISBN 978-0124143609
3. Eggel, A.; Wyss-Coray, T. (2014). "Parabiosis for the study of age-related chronic disease". Swiss Medical Weekly. 144: 13914. doi:10.4414/smw.2014.13914. PMC 4082987. PMID 24496774.
4. Harris, R. B. S. (2013). "Is Leptin the Parabiotic "Satiety" Factor ? Past and Present Interpretations". Appetite. 61 (1): 111–118. doi:10.1016/j.appet.2012.08.006. PMC 3749919. PMID 22889986.
5. Hervey, G. R. (1959). "The effects of lesions in the hypothalamus in parabiotic rats". The Journal of Physiology. 145 (2): 336–352. doi:10.1113/jphysiol.1959.sp006145. PMC 1356830. PMID 13642304.
6. Coleman, D (2010). "A historical perspective on leptin". Nature Medicine. 16 (10): 1097–1099. doi:10.1038/nm1010-1097. PMID 20930752. S2CID 21890417.
7. Friedell, G. H.; Sommers, S. C.; Chute, R. N.; Warren, S. (1966). "Ovarian tumorigenesis in irradiated parabiotic rats". Cancer Research. 3 (3): 427–434. PMID 5930688.
8. Pluvinage, John V.; Wyss-Coray, Tony (February 2020). "Systemic factors as mediators of brain homeostasis, ageing and neurodegeneration". Nature Reviews Neuroscience. 21 (2): 93–102. doi:10.1038/s41583-019-0255-9. ISSN 1471-003X. PMID 31913356. S2CID 210044841.
9. Ruckh, Julia M.; Zhao, Jing-Wei; Shadrach, Jennifer L.; Peter; Nageswara Rao, Tata; Wagers, Amy J.; Franklin, Robin J.M. (2012). "Rejuvenation of Regeneration in the Aging Central Nervous System". Cell Stem Cell. 10 (1): 96–103. doi:10.1016/j.stem.2011.11.019. PMC 3714794. PMID 22226359.
10. "Parabiosis Definition & Meaning - Merriam-Webster".
11. Rohde, Klaus. Marine Parasitology. CSIRO Publishing 2005. ISBN 978-0643090255
12. Haynes, Alan R., Coile, Nancy C., Schubert. Timothy S.; "Comparison of Two Parasitic Vines: Dodder (Cuscuta) and Woe Vine (Cassytha)." Botany Circular No. 30. Fla. Dept Agric. & Consumer Services January/February 1996. Division of Plant Industry
13. Wheeler, William Morton (1921). "A New Case of Parabiosis and the "Ant Gardens" of British Guiana". Ecology. 2 (2): 89–103. Bibcode:1921Ecol....2...89W. doi:10.2307/1928921. JSTOR 1928921.
14. Swain, R. B. (1980). "Trophic competition among parabiotic ants". Insectes Sociaux. 27 (4): 377–390. doi:10.1007/BF02223730. S2CID 39194355.
15. Menzel, Florian; Linsenmair, Karl Eduard; Blüthgen, Nico (2008). "Selective interspecific tolerance in tropical Crematogaster–Camponotus associations". Animal Behaviour. 75 (3): 837–846. doi:10.1016/j.anbehav.2007.07.005. S2CID 140210373.
16. Menzel, F.; Blüthgen, N. (2010). "Parabiotic associations between tropical ants: equal partnership or parasitic exploitation?". Journal of Animal Ecology. 79 (1): 71–81. Bibcode:2010JAnEc..79...71M. doi:10.1111/j.1365-2656.2009.01628.x. PMID 19891712.