Project Details
Projekt
KFO 126: Selfish Brain: Brain Glucose and Metabolic Syndrome
Subject Area
Medicine
Term
from 2005 to 2010
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5397495
The exact regulation of brain glucose level in higher organisms is crucial to their survival. A lack of brain glucose can not only generate cognitive dysfunction, very low blood glucose levels can cause convulsions, loss of consciousness, and in the worst case even lead to death. There is a traditional paradigm concerning blood glucose regulation. The 14th edition of Harrison s Principals of internal medicine states, The maintenance of plasma glucose concentrations within narrow bounds is essential for health. Here, we formulate a novel paradigm, by changing plasma glucose into brain glucose .
This novel and fundamental paradigm has been extensively discussed in our Review The Selfish Brain: Competition for Energy Resources (Neuroscience Biobehavioral Reviews, 2004). This basic paradigm is the link of all our projects. The main goal of the Clinical Research Unit is to prepare a change in paradigm by establishing a novel point of view.
Our theory comprises four basic principles:
-- First, the brain prioritises the adjustment of its own ATP concentration. High and low affinity ATP-sensitive potassium channels regulate the brain s self-allocation of glucose.
-- Second, brain ATP regulation is a learning control process. The self-allocation process is under short-term and long-term feedback control by cortisol and its high and low-affinity receptors.
-- Third, the brain uses cortical plasticity to stabilise the self-allocation process in the long run. After a stressful experience, a newly achieved consolidation and stabilisation of the self-allocation process may allow the brain to reappraise its energy demand strategies.
-- Fourth, alterations in glucose allocation can be compensated by changes in food intake or by utilisation of alternate substrates such as lactate or ketones. Alternative strategies of the brain to safeguard its energy needs can result in diseases like obesity and type 2 diabetes mellitus.
In contrast to conventional models our paradigm alters the hierarchy of regulated parameters by prioritising the energy demand of the brain and giving it a supreme authority. The dimension of adipose tissue as well as the dimension of muscle tissue becomes a regulating goal of second order. According to this idea obesity and type 2 diabetes are central diseases of the brain on the basis of neuroendocrine defects. Efforts to prevent and treat obesity can therefore only be successful when taking into account these crucial aspects.
This novel and fundamental paradigm has been extensively discussed in our Review The Selfish Brain: Competition for Energy Resources (Neuroscience Biobehavioral Reviews, 2004). This basic paradigm is the link of all our projects. The main goal of the Clinical Research Unit is to prepare a change in paradigm by establishing a novel point of view.
Our theory comprises four basic principles:
-- First, the brain prioritises the adjustment of its own ATP concentration. High and low affinity ATP-sensitive potassium channels regulate the brain s self-allocation of glucose.
-- Second, brain ATP regulation is a learning control process. The self-allocation process is under short-term and long-term feedback control by cortisol and its high and low-affinity receptors.
-- Third, the brain uses cortical plasticity to stabilise the self-allocation process in the long run. After a stressful experience, a newly achieved consolidation and stabilisation of the self-allocation process may allow the brain to reappraise its energy demand strategies.
-- Fourth, alterations in glucose allocation can be compensated by changes in food intake or by utilisation of alternate substrates such as lactate or ketones. Alternative strategies of the brain to safeguard its energy needs can result in diseases like obesity and type 2 diabetes mellitus.
In contrast to conventional models our paradigm alters the hierarchy of regulated parameters by prioritising the energy demand of the brain and giving it a supreme authority. The dimension of adipose tissue as well as the dimension of muscle tissue becomes a regulating goal of second order. According to this idea obesity and type 2 diabetes are central diseases of the brain on the basis of neuroendocrine defects. Efforts to prevent and treat obesity can therefore only be successful when taking into account these crucial aspects.
DFG Programme
Clinical Research Units
International Connection
Switzerland
Projects
- Charakterisierung von Allokationssystem und ingestivem Verhalten bei Patienten mit metabolischen und psychischen Störungen (Applicant Schweiger, Ulrich )
- Die Rolle des Gehirncorticosteroid Feedbacks für die Glukoseregulation (Applicant Peters, Achim )
- Gehirnglukose: Bluthirnschranke und ATP sensitive Kalium Kanäle (Applicant Moser, Andreas )
- Glukose und alternative Energiesubstrate als Modulator von Appetit und Nahrungsaufnahme (Applicant Schultes, Bernd )
- Ingestion und Kognition - Der Einfluss von Antizipation, Perzeption und Schlafentzug auf die Nahrungsaufnahme (Applicant Hallschmid, Manfred )
- Metabolisches Lernen - Wird die Adaptation an wiederholte Hypoglykämien durch glutamaterge Mechanismen vermittelt? (Applicant Pais, Isabel )
- NMR Untersuchungen zur molekularen Basis des Pull-Prinzips beim Astrocyten-Neuronen Shuttle (Applicant Peters, Thomas )
- VEGF-Synthese in kultivierten Nerven-- und Gliazellen (Applicant Jelkmann, Wolfgang )
- Viral-gestörter zerebraler Metabolismus (Applicant Mesters, Jeroen )
- Zelluläre Mechanismen im Pull-Prinzip (Applicant Jöhren, Olaf )
- Zentrales Glukose-Feedback und Gehirn-Kortikosteroid-Feedback im Energie Push-Pull-Prinzip (Applicant Peters, Achim )
- Zerebraler Energiemetabolismus und Allokation bei neuronaler Aktivierung/Inhibition (Applicant Oltmanns, Kerstin )
Spokesperson
Professor Dr. Fritz Hohagen
Leader
Professor Dr. Achim Peters
