Changes in kinetics of amino acid uptake at the ageing ovine blood-cerebrospinal fluid barrier.
Amino acids (AA) in brain are precisely controlled by blood-brain barriers, which undergo a host of changes in both morphology and function during ageing. The effect of these age-related changes on AA homeostasis in brain is not well described. This study investigated the kinetics of four AA (Leu, Phe, Ala and Lys) uptakes at young and old ovine choroid plexus (CP), the blood-cerebrospinal fluid (CSF) barrier (BCB), and measured AA concentrations in CSF and plasma samples. In old sheep, the weight of lateral CP increased, so did the ratio of CP/brain. The expansion of the CP is consistent with clinical observation of thicker leptomeninges in old age. AA concentrations in old CSF, plasma and their ratio were different from the young. Both V(max) and K(m) of Phe and Lys were significant higher compared to the young, indicating higher trans-stimulation in old BCB. Cross-competition and kinetic inhibition studies found the sensitivity and specificity of these transporters were impaired in old BCB. These changes may be the first signs of a compromised barrier system in ageing brain leading increased AA influx into the brain causing neurotoxicity.
Chen
R L
RL
Pharmaceutical Science Division, School of Biomedical & Health Sciences, King's College London, London SE1 1UL, UK. ruolichen@gmail.com
Preston
J E
JE
D000375:Aging / Q000378:metabolism*; D000596:Amino Acids / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006706:Homeostasis; D018377:Neurotransmitter Agents / Q000378:metabolism; D012756:Sheep
D000596:Amino Acids; D018377:Neurotransmitter Agents