Parabiosis#Natural examples

file:the Biological bulletin (19755290053).jpg 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.Biju Parekkadan & Martin L. Yarmush (eds). Stem Cell Bioengineering. Chapter 10: "Parabiosis in aging research and regenerative medicine" Artech House 2009 {{ISBN|978-1596934023}}Zarrow, M. X. Experimental Endocrinology: A Sourcebook of Basic Techniques Academic Press 1964 {{ISBN|978-0124143609}} 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.{{cite journal | last1 = Eggel | first1 = A. | last2 = Wyss-Coray | first2 = T. | year = 2014 | title = Parabiosis for the study of age-related chronic disease | journal = Swiss Medical Weekly | volume = 144 | page = 13914 | doi = 10.4414/smw.2014.13914|pmid=24496774|pmc=4082987}}

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.{{cite journal|last1=Harris|first1=R. B. S.|year=2013|title=Is Leptin the Parabiotic "Satiety" Factor ? Past and Present Interpretations|journal=Appetite|volume=61|issue=1|pages=111–118|doi=10.1016/j.appet.2012.08.006|pmc=3749919|pmid=22889986}}

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.{{cite journal | last1 = Hervey | first1 = G. R. | year = 1959 | title = The effects of lesions in the hypothalamus in parabiotic rats | journal = The Journal of Physiology | volume = 145 | issue = 2| pages = 336–352 | doi=10.1113/jphysiol.1959.sp006145| pmc = 1356830 | pmid=13642304}}{{cite journal | last1 = Coleman | first1 = D | year = 2010 | title = A historical perspective on leptin | journal = Nature Medicine | volume = 16 | issue = 10| pages = 1097–1099 | doi=10.1038/nm1010-1097| pmid = 20930752 | s2cid = 21890417 }}

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.

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.{{cite journal | last1 = Friedell | first1 = G. H. | last2 = Sommers | first2 = S. C. | last3 = Chute | first3 = R. N. | last4 = Warren | first4 = S. | year = 1966 | title = Ovarian tumorigenesis in irradiated parabiotic rats | journal = Cancer Research | volume = 3 | issue = 3| pages = 427–434 | pmid = 5930688 }}

{{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.{{Cite journal|last1=Pluvinage|first1=John V.|last2=Wyss-Coray|first2=Tony|date=February 2020|title=Systemic factors as mediators of brain homeostasis, ageing and neurodegeneration|url=http://www.nature.com/articles/s41583-019-0255-9|journal=Nature Reviews Neuroscience|language=en|volume=21|issue=2|pages=93–102|doi=10.1038/s41583-019-0255-9|pmid=31913356|s2cid=210044841|issn=1471-003X|url-access=subscription}} 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.{{cite journal | last1 = Ruckh | first1 = Julia M. | last2 = Zhao | first2 = Jing-Wei | last3 = Shadrach | first3 = Jennifer L. | last4 = Peter | last5 = Nageswara Rao | first5 = Tata | last6 = Wagers | first6 = Amy J. | last7 = Franklin | first7 = Robin J.M. | year = 2012 | title = Rejuvenation of Regeneration in the Aging Central Nervous System | journal = Cell Stem Cell | volume = 10 | issue = 1| pages = 96–103 | doi=10.1016/j.stem.2011.11.019| pmc = 3714794 | pmid=22226359}}

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.{{cite journal | last1 = Ruckh | first1 = Julia M. | last2 = Zhao | first2 = Jing-Wei | last3 = Shadrach | first3 = Jennifer L. | last4 = Peter | last5 = Nageswara Rao | first5 = Tata | last6 = Wagers | first6 = Amy J. | last7 = Franklin | first7 = Robin J.M. | year = 2012 | title = Rejuvenation of Regeneration in the Aging Central Nervous System | journal = Cell Stem Cell | volume = 10 | issue = 1| pages = 96–103 | doi=10.1016/j.stem.2011.11.019| pmc = 3714794 | pmid=22226359}}<

Studies using heterochronic parabiosis have shown that exposure of old mice to young blood can reverse some age-related impairments in multiple tissues, including the brain, liver, heart, and skeletal muscle. Conversely, young mice exposed to old blood often show signs of accelerated aging.

• In a landmark study, Villeda et al. (2011) found that young blood improved neurogenesis and synaptic plasticity in aged mice.{{Cite journal |last1=Villeda |first1=Saul A. |last2=Plambeck |first2=Kimberly E. |last3=Wyss-Coray |first3=Tony |title=Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice |journal=Nature |volume=477 |issue=7362 |pages=90–94 |year=2011 |doi=10.1038/nature10357 |pmid=21886161|pmc=3170097 }}

• Subsequent work by Conboy et al. showed that rejuvenation effects are mediated not just by beneficial factors in young blood, but also by dilution or suppression of age-related inhibitory signals.{{Cite journal |last1=Conboy |first1=Irina M. |last2=Conboy |first2=Michael J. |last3=Wagers |first3=Amy J. |title=Rejuvenation of aged progenitor cells by exposure to a young systemic environment |journal=Nature |volume=433 |issue=7027 |pages=760–764 |year=2005 |doi=10.1038/nature03260 |pmid=15716955}}

The term is also applicable to spontaneously occurring conditions such as in conjoined twins.{{cite web| url = http://www.merriam-webster.com/dictionary/parabiosis?show=0&t=1386697129| title = Parabiosis Definition & Meaning - Merriam-Webster}}

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.Rohde, Klaus. Marine Parasitology. CSIRO Publishing 2005. {{ISBN|978-0643090255}}

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.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

file:Shattuck 53813, Crematogaster modiglianii and Camponotus rufifemur parabiosis, Danum Valley, Sabah-web (5042353719) (2).jpg 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.{{cite journal | last1 = Wheeler | first1 = William Morton | year = 1921 | title = A New Case of Parabiosis and the "Ant Gardens" of British Guiana | journal = Ecology | volume = 2 | issue = 2| pages = 89–103 | jstor=1928921 | doi=10.2307/1928921| bibcode = 1921Ecol....2...89W | url = https://zenodo.org/record/25181 }}{{cite journal | last1 = Swain | first1 = R. B. | year = 1980 | title = Trophic competition among parabiotic ants | journal = Insectes Sociaux | volume = 27 | issue = 4| pages = 377–390 | doi = 10.1007/BF02223730 | s2cid = 39194355 }} Furthermore, there is evidence for the partitioning of functions of work between the two species in the nest.{{cite journal | last1 = Menzel | first1 = Florian | last2 = Linsenmair | first2 = Karl Eduard | last3 = Blüthgen | first3 = Nico | year = 2008 | title = Selective interspecific tolerance in tropical Crematogaster–Camponotus associations | journal = Animal Behaviour | volume = 75 | issue = 3| pages = 837–846 | doi = 10.1016/j.anbehav.2007.07.005 | s2cid = 140210373 }} 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. Benefits from shared nest defence and maintenance even when there is neither direct cooperation nor interaction between the two associated populations in a nest.{{cite journal | last1 = Menzel | first1 = F. | last2 = Blüthgen | first2 = N. | year = 2010 | title = Parabiotic associations between tropical ants: equal partnership or parasitic exploitation? | journal = Journal of Animal Ecology | volume = 79 | issue = 1| pages = 71–81 | doi = 10.1111/j.1365-2656.2009.01628.x | pmid = 19891712 | doi-access = free | bibcode = 2010JAnEc..79...71M }}

Parabiosis derives most directly from Neo-Latin, 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."

• {{annotated link|Aging research}}
• {{annotated link|Commensalism}}
• {{annotated link|Mutualism (biology)}}
• {{annotated link|Neurogenesis}}
• {{annotated link|Senescence}}
• {{annotated link|Stem cell niche}}
• {{annotated link|Symbiosis}}

{{reflist}}

• [https://www.nature.com/articles/nature10357 Nature article on young blood and cognitive rejuvenation]
• [https://www.cell.com/cell/fulltext/S0092-8674(21)00287-1 Recent studies on plasma dilution and aging reversal]

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