Brain Plasticity: Measuring Protein Synthesis Rates in the Human Brain

Abstract

IntroductionBrain plasticity is a term typically used to refer to the ability of the brain to reorganize itself throughout life. Though the term is often applied in neuroscience to express synaptic or non‐synaptic plasticity, information on whether neuroplasticity is also accompanied by a high brain tissue protein turnover rate is scarce. Because of obvious limitations with regard to brain tissue sampling no study has ever directly measured brain protein synthesis rates in vivo in humans. In this study, we applied contemporary stable isotope methodology to assess protein synthesis rates in vivo in human brain tissue of patients operated for drug‐resistant epilepsy.MethodsSix otherwise healthy patients (47±6 y), scheduled to undergo resective surgery for treatment of drug‐resistant temporomesial epilepsy, were included in this study. Primed continuous intravenous infusions with L‐[ring‐13C6]‐Phenylalanine and L‐[3,5‐2H2]‐Tyrosine were initiated 2.5 h prior to surgery and continued during surgery. Throughout the surgical procedure the following tissue samples were obtained: temporal neocortex, hippocampus, temporalis muscle, and vastus lateralis muscle. Tissue‐specific fractional protein synthesis rates (%/h) were assessed by measuring the incorporation of labelled L‐[ring‐13C6]‐Phenylalanine in tissue protein and were compared between the different tissues using a paired t test.ResultsSerum L‐[ring‐13C6]‐Phenylalanine enrichments averaged 8.1±0.7 MPE throughout the surgical procedure. Protein synthesis rates of temporal neocortex and hippocampus tissue averaged 0.17±0.01 and 0.13±0.01 %/h, respectively, with a significant difference between both tissues (P<0.05). Brain tissue protein synthesis rates were 3–4 fold higher compared to skeletal muscle protein synthesis rates (0.05±0.01 %/h; P<0.001).ConclusionThis is the first study to present protein synthesis rates in vivo in the human brain. With brain protein synthesis rates being several‐fold higher compared to skeletal muscle protein synthesis rates, the human brain displays a degree of tissue plasticity much higher than generally assumed.