scholarly journals Brain More Resistant to Energy Restriction Than Body: A Systematic Review

2021 ◽  
Vol 15 ◽  
Author(s):  
Marie Sprengell ◽  
Britta Kubera ◽  
Achim Peters

The gluco-lipostatic theory and its modern variants assume that blood glucose and energy stores are controlled in closed-loop feedback processes. The Selfish Brain theory is based on the same assumptions, but additionally postulates that the brain, as an independent energy compartment, self-regulates its energy concentration with the highest priority. In some clinical situations these two theories make opposite predictions. To investigate one of these situations, namely caloric restriction, we formulated a hypothesis which, if confirmed, would match the predictions of the Selfish Brain theory—but not those of the gluco-lipostatic theory. Hypothesis: Calorie restriction causes minor mass (energy) changes in the brain as opposed to major changes in the body. We conducted a systematic review of caloric-restriction studies to test whether or not the evaluated studies confirmed this hypothesis. We identified 3,157 records, screened 2,804 works by title or abstract, and analyzed 232 by full text. According to strict selection criteria (set out in our PROSPERO preregistration, complying with PRISMA guidelines, and the pre-defined hypothesis-decision algorithm), 8 papers provided enough information to decide on the hypothesis: In animals, high-energy phosphates were measured by 31P-nuclear magnetic resonance, and organ and total body weights were measured by scales, while in humans organ sizes were determined by magnetic resonance imaging. All 8 decidable papers confirmed the hypothesis, none spoke against it. The evidence presented here clearly shows that the most accurate predictions are possible with a theory that regards the brain as independently self-regulating and as occupying a primary position in a hierarchically organized energy metabolism.

2021 ◽  
Vol 15 ◽  
Author(s):  
Marie Sprengell ◽  
Britta Kubera ◽  
Achim Peters

This work joins a series that methodically tests the predictions of the Selfish-Brain theory. The theory postulates a vital ability of the mammalian brain, namely to give priority to its own energy metabolism. The brain behaves “selfishly” in this respect. For the cerebral artery occlusion studied here, the theory predicts an increase in blood glucose concentration, what becomes the hypothesis to be tested. We conducted a systematic review of cerebral-artery-occlusion papers to test whether or not the included studies could confirm this hypothesis. We identified 239 records, screened 231 works by title or abstract, and analyzed 89 by full text. According to strict selection criteria (set out in our PROSPERO preregistration, complying with PRISMA guidelines), 7 papers provided enough information to decide on the hypothesis. Our hypothesis could be fully confirmed for the 3 to 24 h after the onset of a transient 2 h or permanent occlusion. As for the mechanism, the theory predicts that the energy-deprived brain suppresses insulin secretion via the sympathoadrenal system, thereby preventing insulin-mediated glucose uptake into muscle and fat and, as a result, enhancing insulin-independent glucose uptake via the blood-brain barrier. Evidence from our included studies actually demonstrated cerebral insulin suppression. In all, the current work confirms the second major prediction of the Selfish-Brain theory that relates to a proximal bottleneck of the cerebral supply chain, cerebral artery occlusion. Its first major prediction relates to a distal supply bottleneck, caloric restriction, and is fulfilled as shown by our previous work, whereas the prediction of the long held gluco-lipostatic theory, which sees the brain as only passively supplied, is violated (Sprengell et al., 2021). The crucial point was that caloric restriction elicits smaller changes in mass (energy) in the brain than in the body. Taken together, the evidence from the current and previous work clearly shows that the most accurate predictions are possible with a theory that views the brain as an independently self-regulating energy compartment occupying a primary position in energy metabolism.


2021 ◽  
Vol 15 ◽  
Author(s):  
Marie Sprengell ◽  
Britta Kubera ◽  
Achim Peters

Cerebral energy supply is determined by the energy content of the blood. Accordingly, the brain is undersupplied during hypoglycaemia. Whether or not there is an additional cerebral energy demand that depends upon the energy content of the brain is considered differently in two opposing theoretical approaches. The Selfish-Brain theory postulates that the brain actively demands energy from the body when needed, while long-held theories, the gluco-lipostatic theory and its variants, deny such active brain involvement and view the brain as purely passively supplied. Here we put the competing theories to the test. We conducted a systematic review of a condition in which the rival theories make opposite predictions, i.e., experimental T1DM. The Selfish-Brain theory predicts that induction of experimental type 1 diabetes causes minor mass (energy) changes in the brain as opposed to major glucose changes in the blood. This prediction becomes our hypothesis to be tested here. A total of 608 works were screened by title and abstract, and 64 were analysed in full text. According to strict selection criteria defined in our PROSPERO preannouncement and complying with PRISMA guidelines, 18 studies met all inclusion criteria. Thirteen studies provided sufficient data to test our hypothesis. The 13 evaluable studies (15 experiments) showed that the diabetic groups had blood glucose concentrations that differed from controls by +294 ± 96% (mean ± standard deviation) and brain mass (energy) that differed from controls by −4 ± 13%, such that blood changes were an order of magnitude greater than brain changes (T = 11.5, df = 14, p < 0.001). This finding confirms not only our hypothesis but also the prediction of the Selfish-Brain theory, while the predictions of the gluco-lipostatic theory and its variants were violated. The current paper completes a three-part series of systematic reviews, the two previous papers deal with a distal and a proximal bottleneck in the cerebral brain supply, i.e., caloric restriction and cerebral artery occlusion. All three papers demonstrate that accurate predictions are only possible if one regards the brain as an organ that regulates its energy concentrations independently and occupies a primary position in a hierarchically organised energy metabolism.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=156816, PROSPERO, identifier: CRD42020156816.


Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 328-333 ◽  
Author(s):  
D NF Harris ◽  
J A Wilson ◽  
S D Taylor-Robinson ◽  
K M Taylor

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 ± 0.86 vs after: 2.57 ± 1.31; mean ± 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 ± 0.04 vs 7.16 ± 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 ± 0.37 vs 6.39 ± 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Frederic Alexandre

AbstractThe brain is a complex system, due to the heterogeneity of its structure, the diversity of the functions in which it participates and to its reciprocal relationships with the body and the environment. A systemic description of the brain is presented here, as a contribution to developing a brain theory and as a general framework where specific models in computational neuroscience can be integrated and associated with global information flows and cognitive functions. In an enactive view, this framework integrates the fundamental organization of the brain in sensorimotor loops with the internal and the external worlds, answering four fundamental questions (what, why, where and how). Our survival-oriented definition of behavior gives a prominent role to pavlovian and instrumental conditioning, augmented during phylogeny by the specific contribution of other kinds of learning, related to semantic memory in the posterior cortex, episodic memory in the hippocampus and working memory in the frontal cortex. This framework highlights that responses can be prepared in different ways, from pavlovian reflexes and habitual behavior to deliberations for goal-directed planning and reasoning, and explains that these different kinds of responses coexist, collaborate and compete for the control of behavior. It also lays emphasis on the fact that cognition can be described as a dynamical system of interacting memories, some acting to provide information to others, to replace them when they are not efficient enough, or to help for their improvement. Describing the brain as an architecture of learning systems has also strong implications in Machine Learning. Our biologically informed view of pavlovian and instrumental conditioning can be very precious to revisit classical Reinforcement Learning and provide a basis to ensure really autonomous learning.


2005 ◽  
Vol 288 (2) ◽  
pp. G292-G299 ◽  
Author(s):  
Ronald J. Jandacek ◽  
Nicole Anderson ◽  
Min Liu ◽  
Shuqin Zheng ◽  
Qing Yang ◽  
...  

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other tissues. We have studied the reversibility of this process in mice that followed a regimen of body weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss (“yo-yo diet regimen”). We measured the distribution of orally gavaged [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in a threefold increase of 14C amount and concentration in the brain. After weight regain, 14C in the brain decreased but then increased again after a second weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue without changing the total amount in that tissue. Weight loss and regain resulted in an increase of 14C in the liver, which reflected an increase of fat in the liver. The regimen of weight gain and loss was repeated in mice gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric restriction caused a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by dietary olestra.


1991 ◽  
Vol 277 (3) ◽  
pp. 697-703 ◽  
Author(s):  
R A Hawkins ◽  
J Jessy

1. It has been established that chronic hyperammonaemia, whether caused by portacaval shunting or other means, leads to a variety of metabolic changes, including a depression in the cerebral metabolic rate of glucose (CMRGlc) increased permeability of the blood-brain barrier to neutral amino acids, and an increase in the brain content of aromatic amino acids. The preceding paper [Jessy, DeJoseph & Hawkins (1991) Biochem. J. 277, 693-696] showed that the depression in CMRGlc caused by hyperammonaemia correlated more closely with glutamine, a metabolite of ammonia, than with ammonia itself. This suggested that ammonia (NH3 and NH4+) was without effect. The present experiments address the question whether ammonia, in the absence of net glutamine synthesis, induces any of the metabolic symptoms of cerebral dysfunction associated with hyperammonaemia. 2. Small doses of methionine sulphoximine, an inhibitor of glutamine synthetase, were used to raise the plasma ammonia levels of normal rats without increasing the brain glutamine content. These hyperammonaemic rats, with plasma and brain ammonia levels equivalent to those known to depress brain function, behaved normally over 48 h. There was no depression of cerebral energy metabolism (i.e. the rate of glucose consumption). Contents of key intermediary metabolites and high-energy phosphates were normal. Neutral amino acid transport (tryptophan and leucine) and the brain contents of aromatic amino acids were unchanged. 3. The data suggest that ammonia is without effect at concentrations less than 1 mumol/ml if it is not converted into glutamine. The deleterious effect of chronic hyperammonaemia seems to begin with the synthesis of glutamine.


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