Area postrema

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Area postrema
Rhomboid fossa. (Area postrema labeled at bottom center.)
Human caudal brainstem posterior view description (Area postrema is #8)
Details
Part ofMedulla
Identifiers
Acronym(s)AP
MeSHD031608
NeuroNames772
NeuroLex IDbirnlex_2636
TA98A14.1.04.258
TA26009
FMA72607
Anatomical terms of neuroanatomy

The area postrema, a paired structure in the

circumventricular organ having permeable capillaries and sensory neurons that enable its dual role to detect circulating chemical messengers in the blood and transduce them into neural signals and networks.[2][3][4] Its position adjacent to the bilateral nuclei of the solitary tract and role as a sensory transducer allow it to integrate blood-to-brain autonomic functions. Such roles of the area postrema include its detection of circulating hormones involved in vomiting, thirst, hunger, and blood pressure control.[1][5]

Structure

The area postrema is a paired protuberance found at the inferoposterior limit of the

tanycytes can participate in the transport of neurochemicals into and out of the cerebrospinal fluid from its cells or adjacent neurons, glia or vessels. Ependyma and tanycytes may also participate in chemoreception.[1][5]

The area postrema is considered a

sinusoidal.[6] Subregional capillary density of the area postrema was highest near the ventricular interface, and was nearly twice as dense as the capillary densities of the adjacent solitary nucleus (SN), and dorsal motor nucleus of the vagus nerve.[6] A tanycyte barrier partially compensates for high capillary permeability in the area postrema.[7]

blood flow and transit time for blood markers relatively slow, thereby amplifying the sensing capability for circulating compounds, such as hormones or transmitters.[8]

Micrograph of the area postrema (arrows) in a transverse section through the lower brainstem of a squirrel monkey (Saimiri sciureus). Hematoxylin and eosin stain; Bar=100 microns (0.1 millimeter).

Connections

The area postrema connects to the

dorsal motor nucleus
of the vagus and the NTS.

emetic inputs. However, this structure plays no key role for nausea induced by the activation of vagal nerve fibers or by motion, and its function in radiation-induced vomiting remains unclear.[9]

Because the area postrema and a specialized region of NTS have permeable capillaries,[2] peptides and other hormonal signals in the blood have direct access to neurons of brain areas with vital roles in the autonomic control of the body.[2][6] As a result, the area postrema is considered a site of integration for various physiological signals in the blood as they enter the central nervous system.[2][3]

Function

Chemoreception

The area postrema, one of the circumventricular organs,[10] detects toxins in the blood and acts as a vomit-inducing center. The area postrema is a critical homeostatic integration center for humoral and neural signals by means of its function as a chemoreceptor trigger zone for vomiting in response to emetic drugs. It is a densely vascularized structure with subregional capillary specializations for high permeability for circulating blood signals, allowing it to detect various chemical messengers in the blood and cerebrospinal fluid.[4][6] Capillary blood flow appears to be uniquely slow in the area postrema, prolonging the contact time for blood-borne hormones to interact with neuronal receptors involved in regulation of blood pressure, body fluids, and emetic responses.[4][8]

Autonomic regulation

The

arterial blood pressure without producing considerable changes in the heart rate, an effect mediated by the area postrema.[11]

Clinical significance

Damage

Damage to the area postrema, caused primarily by lesioning or

sensory neurons of the stomach, intestines, liver, kidneys, heart, and other internal organs, a variety of physiological reflexes rely on the area postrema to transfer information. The area postrema acts to directly monitor the chemical status of the organism. Lesions of the area postrema are sometimes referred to as 'central vagotomy' because they eliminate the brain's ability to monitor the physiological status of the body through its vagus nerve.[12] These lesions thus serve to prevent the detection of poisons and consequently prevent the body's natural defenses from kicking in. In one example, experiments done by Bernstein et al. on rats indicated that the area postrema lesions prevented the detection of lithium chloride, which can become toxic at high concentrations. Since the rats could not detect the chemical, they were not able to employ a psychological procedure known as taste aversion conditioning, causing the rat to continuously ingest the lithium-paired saccharin solution. These findings indicate that rats with area postrema lesions do not acquire the normal conditioned taste aversions when lithium chloride is used as the unconditioned stimulus. In addition to simple taste aversions, rats with the area postrema lesions failed to perform other behavioral and physiological responses associated with the introduction of the toxin and present in the control group, such as lying down on their bellies, delayed stomach emptying, and hypothermia.[13]
Such experimentation emphasizes the significance of the area postrema not only in the identification of toxic substances in the body but also in the many physical responses to the toxin.

Effect of dopamine

The area postrema also has a significant role in the discussion of Parkinson's disease. Drugs that treat Parkinson's disease using dopamine have a strong effect on the area postrema. These drugs stimulate dopamine transmission and attempt to normalize motor functions affected by Parkinson's. This works because nerve cells, in particular, in the basal ganglia, which has a crucial role in the regulation of movement and is the primary site for the pathology of Parkinson's, use dopamine as their neurotransmitter and are activated by medications that increase the concentrations of the dopamine or work to stimulate the dopamine receptors. Dopamine also manages to stimulate the area postrema, since this part of the brain contains a high density of dopamine receptors. The area postrema is very sensitive to changes in blood toxicity and senses the presence of poisonous or dangerous substances in the blood. As a defense mechanism, the area postrema induces vomiting to prevent further intoxication. The high density of dopamine receptors in the area postrema makes it very sensitive to the dopamine-enhancing drugs. Stimulation of the dopamine receptors in the area postrema activates these vomiting centers of the brain; this is why nausea is one of the most common side-effects of antiparkinsonian drugs.[14]

History

The area postrema was first named and located in the gross anatomy of the brain by Magnus Gustaf Retzius, a Swedish anatomist, anthropologist and professor of histology. In 1896, he published a two-volume monograph on the gross anatomy of the human brain in which the area postrema was mentioned.[citation needed] In 1975, evidence of neurons in the area postrema of several mammal species was published.[15]

Scientists became increasingly interested in the research of vomiting in the 1950s, perhaps in part due to society's heightened awareness of

lateral reticular formation of the medulla oblongata.[citation needed
]

In 1953, Borison and Wang determined that the chemosensor area acted as a vomiting trigger zone in the brain stem, which they named the chemoreceptor trigger zone (CTZ) for emesis. Using cats and dogs as model organisms, they found that the removal of this trigger zone from the brain allowed for the prevention of emesis in the animals directly following injection of certain chemicals into the blood, demonstrating the existence of a relationship between the trigger zone and the act of vomiting. The CTZ was anatomically located in the area postrema of the medulla oblongata. The area postrema had been anatomically identified and named nearly 60 years earlier, but its function had remained unknown until its role in emesis was later confirmed.[16]

Current research

Research has continued today around the world on the functions of the area postrema. Beyond its role in emesis, as studied intensely by the researchers of the mid-1900s, the activity of the area postrema has been closely linked to other autonomic functions such as regulation of food intake, body fluid homeostasis, and

electrophysiological studies. In 2007 in Japan, research was performed on the mechanism of excitability of area postrema neurons by extracellular ATP. Voltage clamp whole-cell recording techniques were used on rat brain slices. The results showed that most responses to ATP are excitatory and that they are mediated by particular P2 purinoceptors found in the area postrema.[17] The role of the area postrema in flavor-conditioned aversion and preference was studied in 2001 by researchers at the Brooklyn College at the City University of New York. The experiment tested the effect of area postrema lesions in rats on their ability to learn flavor-conditioned aversion to flavors paired with toxic drug treatments, which indeed showed that lesions of the area postrema leads to impaired flavor aversion learning.[18]
A 2009 study followed the development of the area postrema, using a macaque monkey model in an attempt to identify and characterize
glutamate. Ongoing research continues to unravel discrepancies among various rat, cat, and now macaque monkey models of research.[19]

Potential treatments

A 2002 study in Japan tested a drug that may be of use in curbing the emetic response to drugs that increase dopamine concentrations. The study investigated morphine-induced emesis in ferrets, explaining that morphine exposure triggered dopamine release in the medulla oblongata and in the area postrema by activating opiate receptors, which in turn caused vomiting by the ferrets. Yet a pre-treatment with 6-hydroxydopamine, a dopaminergic neurotoxin, significantly reduced the number of emetic episodes in the ferrets following morphine exposure. This neurotoxin reduced levels of dopamine, noradrenaline, and homovanillic acid, a metabolite of dopamine, and is known to destroy noradrenergic and dopaminergic neurons. Here, 6-hydroxydopamine was injected directly into the medulla oblongata but not in other parts of the brain. This study shows how the dopaminergic pathway in the medulla oblongata may be manipulated in order to reduce the nauseating side-effects associated with so many dopamine-increasing drugs.[20]

Continuing pathological studies

The area postrema is also indicated in an

glycaemic control without causing weight gain. Since the drug acts on the area postrema, the doses must be titrated slowly to avoid inducing nausea in the patient.[21]

There are also studies still currently underway to determine the effect of ablation of the area postrema on

angiotensin II- dependent hypertension is abolished by lesioning of the area postrema.[22][23]
The mechanism for this physiological reaction is still not fully understood, but the area postrema's ability to regulate cardiovascular function presents a very interesting direction for neuroendocrinology.

References

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