2006, Number 1
Neurosurgery in feeding disorders: a possible option?
Fanghänel G, Sánchez-Reyes L, Madrigal A, Velasco CF
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Language: Spanish
References: 26
Page: 28-34
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ABSTRACT
Composition and quantity of food in-taken varies considerably between one meal and another, or between one day and the following. Non biological factors -such as emotional, social, day time, feasibility in the type of food, and cost- are, among others, factors that in some way affect the degree of energy in-take by food, which generally is not related with daily energy expenditure. These phenomena represent an active process of regulation that is characterized by the balance between signs that stimulate hunger, called orexigenics and those that produce satiation to stop intake, called anorexigenics, that promotes the stability in the quantity of corporal energy manifested as fat. In this feeding regulatory process there are many molecular signs that participate and regulate the in-take of behaviour food for homeostasis.There are two hypothalamic centers related with the food intake control: the hunger centre in the lateral hypothalamus and the satiation centre in the ventromedial nucleus. In this control many impulses participate, regulated by substances called neurotransmitters, such as: neuropeptide Y, galanine, orexines for the hunger centre and nor epinephrine, serotonin, and dopamine for the satiation centre.
Insulin reaches the brain through circulation and acts reducing the contribution of energy, it was the first hormonal sign that was implicated in weight control by CNS. The second identified hormone, secreted by the adiposity, was leptin. Both hormones circulate in levels proportional to the corporal fat and get to the CNS in proportion to its plasmatic concentrations.
Receptors as leptin and insulin are expressed by brain neurons involved in the contribution of energy, and the administration of any of both peptides directly to the brain, reduce the in-take of food. The lack of any of these hormones produces the opposite. Leptin has a more important role than insulin in the control of the energetic homeostasis in the CNS. For example, the lack of leptin causes severe obesity with hyperfagia that persists regardless the levels of elevated insulin. In contrast, obesity isn’t induced by the lack of insulin. Insulin has a critic role to promote the storage of fat and the synthesis of leptin through the fat cellule.
The neuropeptide Y, produced in the arcuate nucleus of the hypothalamus has an anabolic effect. The gene of expression and secretion of this peptide in the hypothalamus increases during depletion, in the storage of corporal fat and/or when the signs of leptin/insulin are decreased in the brain. Leptin inhibits the gene of expression of the neuropeptide Y in the arcuate nucleus and the genetic “knockout” of the NPY reduces hyperfagia and obesity in mice ob/ob, indicating that the total response to the lack of leptin requires the signs of the NPY. Other substances like the Agouti protein (AGRP), the orexines (hypocretines A and B) and the concentrations of the melancortin hormone have been added to the molecule candidate list with anabolic effects. Also in the adjoining neurons of the arcuate nucleus, are originated anorexigenic peptides like alfa-MSH (a derivated of the proopiomelancortin, POMC) and CART (transcript protein related with cocaine and amphetamine).
Both types of neurons (NPY/AGRP and POMC/CART) coexpress the leptin receptors. In those situations in which the levels of leptin or insulin are low, the NPY/AGRP neurons activate and the POMC/CART are inhibited. This suggests that the main site of adiposity signs transformation is a neuronal response in the arched nucleus. The link between the lateral hypothalamus and the elevated centers of the brain that regulate hunger and satiation is a very important aspect of the regulation system. There have been typified two types of neuropeptides linked to neurons, that appear to be exclusively of the lateral hypothalamus area: the concentrated melanin hormone (MCH) and the orexines.
At the lateral zone, there have been specified two types of hypothalamic neuropeptides, the orexines A and B, also known as hypocretines 1 and 2, which are cellular bodies of the hypothalamus, especially at the lateral hypothalamus and the perifornical area, which stimulate the appetite in an independent way to other neuropeptides known. On the other hand, the orexines A and B derive (by proteolysis) of a common precursor, and are capable of activating their two respective receptors that work in conjunction with proteins G. The central administration of orexines stimulates the in-take and production of orexines' increase with fasting. These neuropeptides match with the hypocretines described by other authors, with expression in lateral hypothalamus, arched nucleus, septal nucleus and forebrain.
Monoaminergic neurotransmitters
a) Noradrenalin
Noradrenalin is synthesized in different areas of the brain such as the dorsal nucleus of the vague and the locus coeruleus.
Noradrenalin shares the same place with NPY and the injection of both inside the preventricular nucleus increase the in-take of food. The repeated injection can result in weight increase; leptin can inhibit noradrenalin secretion.
b) Dopamine
Critic dependence of the in-take of food in the CNS is given by the dopamine sign, which is implicated in the voluntary lack of the food in-take. Motor alterations associated with the lack of dopamine affect also the alimentary behavior. The dopamine effect over the alimentary behavior varies depending of the studyied area. For example the routes of dopamine in the mesolimbic area contribute to the reward of the in-take of savory food.
c) Serotonin
The 5HT2c receptor of serotonin is implicated in the decrease of the in-take of food and the weight increase, due to its effect in the impulse of the satiation centre. To maintain the homeostasis of normal energy it is necessary that the serotonin sign be intact.
New alternative hypothesis
On one hand, the knowledge of regulation of the appetite-satiety neuroendocrine cycle, and on the other, the new techniques of neuromodulation through stereotaxic surgery, allow to offer an extraordinarily interesting field of research in certain patients with feeding disorders of difficult control and with an increase in the mortality risk. The alternative of controlling specific centers of hunger/satiation regulation, is still a hypothesis, though there are some data that allow us to assume that it could be feasible and we will mention them after.
Current experience Stereotaxic (Latin: stereo, three-dimensional; taxis, positioning) is a modern technique of neurosurgery that allows the localization and precise access to intra-cerebral structures, through a small orifice in the skull. If we have identified the places that regulate the intake of food or satiety, it is feasible that through this technique we can stimulate or inhibit this function and offer the patient an lternative that in theory could be feasible. Some of its possible advantages will be that we are talking about a minimum invasive surgery, generally performezñdd using local anesthesia; patients need a minimum hospitalization stay and surgical risks are minimized. This allows us to predict in the majority of the patients a satisfactory evolution of weight decrease.
The current experience of stereotaxic used in eating disorders is null; everything about it is hypothetic. However, the use of this proceeding for other accepted indications where there is previous experience, has allowed us to obtain interesting data of the evolution of these patients that shows indirectly, that the procedure has influenced in the corporal weight.
We present these indirect results, which motivate us to continue considering its possible use in patients that show the approved profile according to an ethic committee properly authorized.
In depression or bipolar disorder cases, the use of the stereotaxic surgery applying electrodes in the bottom pedunculo thalamic region (ITP), independently that they show an improve in their basal alteration, the patients show a weight increase, inferring a relationship of this area and the one of the hypothalamus for the appetite/satiation control, situation that hypothetically could benefit patients with anorexia nervosa or bulimia.
In the cases with Parkinson Disease, the stereotaxic procedure has been made in the pre-lemniscal (RAPRL) or the subtalamic region (STN) in a unilateral or bilateral way, and although the response hasn’t been uniform, the weight changes showed a decrease, making this a possible alternative to be used in some patients with morbid obesity according to the inclusion criteria.
Final comments
The expectative of stereotaxic surgery in handling patients with difficult to control feeding disorders or with high risk of morbid-mortality, is shown as an hypothesis, that should consider the specific rules of good clinical practices and adjust to the rules of an approved ethics committee, for these procedures.
REFERENCES