Cerebral protein synthesis in a genetic mouse model of phenylketonuria

Autophagy induction by tetrahydrobiopterin deficiency

“…35 In Pah enu2 mouse, PAH activities are minimal in the liver resulting in increased phenylalanine concentration but decreased tyrosine concentration in the brain. 36,37 In the current study, Pah enu2 mice fed a normal diet exhibited significant growth retardation compared with the wild-type control (Fig. 3A and B).…”

Postadolescent Changes in Regional Cerebral Protein Synthesis: AnIn VivoStudy in theFmr1Null Mouse

“…Mice were prepared for studies by insertion under light halothane anesthesia of polyethylene catheters (PE-10) into one femoral artery and one or two femoral veins as described previously (Smith and Kang, 2000). Mice were allowed to recover from the surgery overnight in clear plastic cylinders 13 cm in diameter.…”

“…14 C]leucine as described previously (Smith and Kang, 2000). At the end of the experimental interval, mice were killed by an intravenous injection of sodium pentobarbital, and brains were rapidly removed and frozen in isopentane cooled to Ϫ40°C with dry ice.…”

“…14 C]methylmethacrylate standards as described previously (Smith and Kang, 2000). Autoradiograms were digitized with a pixel size of 11 m by means of a 10-bit DVC-1310 digital camera (DVC, Austin, TX).…”

Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations

“…In addition, it was documented that increased plasma Phe concentration was inversely related to cerebral protein synthesis rate, possibly via impaired LNAA transport across BBB [65] and decreased Tyr incorporation into protein in central nervous system in PKU patients [66]. Saturation of L-amino acid transporter at BBB by increased plasma Phe seems to be a contributing but not pivotal factor to the decreased protein synthesis observed in genetic PKU murine models [67]. By using positron emission tomography to study brain of PKU patients after an intravenous L-[1-( 11 )C]-Tyr administration, Hoeksma and colleagues [68] Aging and Disease • Volume 6, Number 5, October 2015 394 demonstrated a significant negative correlation between plasma Phe levels and the cerebral protein synthesis rate.…”