According to the Selfish Brain theory our brain has a series of (hierarchically ordered) mechanisms in place to maintain constant supply of energy at a certain concentration.
Despite weighing only ~2% of body weight, the brain consumes a disproportionate high amount of energy: ~20%. Knowing that, it should come as no surprise that many physical symptoms linked with poor metabolism (incl. muscular fatigue, obesity, taxed liver function possibly due to alcoholism) are linked with compromised brain function (i.e. migraines, forgetfulness, irritability).
The Selfish Brain theory was put forward by scientist at University of Luebeck in Germany in 2004 and is likely to bring a swift in the way we understand and treat metabolic & personality disorders in the future. [ The theory has its roots in some earlier research in 1997 on addiction (DuPont RL 1997) ]
In clinical practice I consider 3 qualitative markers as a sign of good health: Energy, Mood & Appetite (EMA). When all 3 in are balance the body is 95% of the time thriving. The Selfish Brain theory offers a “simple” model of their intimate relationship.
1. The brain’s unique role in energy management
How the human body manages energy supply to different organs is key for treating chronic illness including: obesity, PCOS, cardiovascular disease & cancer. Energy metabolism is dependent on:
i. energy supply
ii. energy allocation
The brain plays a key role in this process. What gives the brain a unique role in body’s metabolism?
i. It carries important functions for the rest of the body.
Together with the heart the brain is responsible for processes that run on an ongoing basis. Shortage of energy supply to these 2 organs can be life threatening.
ii. It consumes a lot of energy.
Despite its small weight (~2% of total body weight), it consumes a disproportionate high amount of energy ~20%, partly due to the energy needs of neurotransmitter transmission (Attwell D and Laughlin S 2001).
iii. It has low energy storage capacity.
In contrast to most other organs it depends almost entirely on glucose for energy but has limited capacity to store glucose. The liver and (to a lesser extent) the muscles are the body’s main glucose reserves (in the form of glycogen).
iv. It’s access to the blood supply is controlled.
The brain comes in contact with the blood (cardiovascular system) in 2 areas only: the Blood Brain Barrier (BBB) where astrocytes (neuron cells) serve as a filter wall and the Hypothalamus. Due to the high amounts of toxins and pathogens circulating in the blood there may be an evolutionary benefit in this physical protection of the brain.
v. It is able to monitor other organs and affect their function.
Through the Peripheral Nervous System (PNS) the brain is able to record information from other organs as well as control their function.
Accounting for the above idiosyncratic functions, the Selfish Brain theory suggests that the brain:
i. Prioritises its own energy supply before other organs by using the stress system when there is an energy deficit (Allocation)
ii. It subsequently alters appetite to alleviate stress and return to balance (Appetite -> Food intake)
The model has the shape of a fishbone to illustrate the hierarchically structure of the pathway.
2. How does the brain sense if it has enough energy?
Cells in the brain as well as skeletal muscles (Lazdunski M. 1994) sense the levels of energy intracellularly through: ATP-sensitive potassium (Katp) channels. ATP & ADP (the body’s energy currencies) bind on these channels and this way signal availability or lack of energy. In an excitatory neutron adequate levels of ATP (by binding on Katp channels) will trigger the release of glutamate or brain-derived neurotrophic factor (BDNF) while elevated ADP will silence it.
A key feature of the Selfish Brain theory is that the brain has 2 types of Katp channels: high & low affinity. When a cell has relatively low ATP concentrations, high affinity Katp channels are still occupied. On the other hand low affinity Katp channels require high ATP concentration to get occupied. The high affinity Katp channels are found mostly in excitatory neurones (releasing glutamate & Brain-Derived Neurotrophic Factor (BDNF)) while low affinity ones are in inhibitory neurones (releasing γ-amino-butyric acid / GABA) (Ohno-Shosaku T et al., 1993). Both types of are found in the human neocortex (Jiang C et al., 1997).
With low ATP concentrations the glutamateric neurones are dominantly active while at high ATP concentrations the GABA-eric neurones predominate.
It is worth mentioning that at critically reduced ATP both excitatory & inhibitory neurones are inactive – a phenomenon referred to as “global silencing” (Mobbs CV et al., 2001).
3. How does the brain maintain a constant energy level?
The brain according to the Selfish Brain theory has 2 ways to maintain a set energy level. One via moderating the allocation on the currently available energy from the peripheral tissue to itself and a 2nd by demanding more energy from the environment by controlling eating behaviour.
3.1 Brain’s “energy on demand”
In order for the brain to access glucose (energy) available in the blood it needs to “open” the blood-brain barrier (BBB). Glutamate activates the glucose receptors (GLUT1 in the astrocytes) of the BBB and sequentially the glucose enters the brain (Magistretti PJ et al., 1999). GABA on the other hand does not have the same impact in the BBB (Chatton JY et al., 2003).
Glutamate* was also shown to activate the limbic-hypothalamic-pituitary-adrenal (LHPA) axis (Yousef KA et al., 1994). LHPA axis is commonly referred to as the stress or the flight or flight response. By activating the LHPA axis glutamate is able to restrict glucose supply to other organs and preserve it for the brain. The steps are as follows:
Glutamate signals the limbic system that the body is in a stressful state. The limbic system stimulates the sympathetic nervous system (NS) through the Ventromedial part of the Hypothalamus (VMH) resulting in the release of CRH & vasopressin hormones. In this way it tells the pituitary to release ACTH hormone. ACTH is released in the blood and stimulates the production of cortisol from the adrenals. Cortisol finally inhibits the production of insulin from pancreatic β cells and thus the uptake of glucose for certain organs making it available for the brain (Jansen AS et al., 1997). In the Selfish Brain model the allocation of energy takes place in the VMH.
In a state of high energy GABA (a calming neurotransmitter) is also released counteracting glutamate’s excitatory effects. The sympathetic system is not activated and the junctions in the BBB remain tightly closed.
In summary the brain can moderate the allocation on the currently available energy from the peripheral tissue to itself as follows:
When there is low energy in brain, glutamate is released in relatively higher levels than GABA causing 2 effects:
1. the BBB opes and increases the intake of glucose from the blood stream to the brain
2. the Limbic Hypothalamic Pituitary Adrenal (LHPA) axis is activated restricting the supply of glucose in peripheral tissue.
3.2 Requesting energy from the environment
Lateral Hypothalamus (LH) is a key area of the brain where appetite is controlled (Anand BK, Brobeck JR. 1951), although not the only one. Glutamate can stimulate the LH to increase appetite . With the increase of food intake, energy from the environment is enters the body (Stanley BG et al., 1993)
According to the Selfish Brain theory the Neocortex acts at the primary regulatory system for energy and the LHPA axis functions as a secondary. xxx Many more hormones (i.e. Leptin hormone signals the hypothalamus that energy has been stored in the fat tissue (Spanswick D et al., 1997)) can be added to the graph without affecting its hierarchy.
The Selfish Brain theory demonstrates how the brain manipulates the stress response mechanism to moderate energy supply. That’s worth keeping in mind when dealing with mental or eating disorders.
* in particular through glutamate receptors of N-methyl-D-aspartate (NMDA) subtype (Molina PE, Abumrad NN 2001).
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