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Insulin-Like Growth Factor-II Uptake Into Choroid Plexus and Brain of Young and Old Sheep

Pharmaceutical Science Research Division, King's College London, United Kingdom.

Address correspondence to Ruo L. Chen, PhD, Pharmaceutical Science Research Division, King's College London, Guy's Campus, London Bridge, London SE1 1UL. E-mail: ronnie.chen{at}kcl.ac.uk

Insulin-like growth factor II (IGF-II) is a major growth factor in brain and is involved in neuroprotection in later life. However, synthesis and delivery of IGF-II to brain by the choroid plexus (CP) in later life is not well understood. This study investigated these issues in old sheep (7–10 years) in comparison to young adult sheep (1–2 years). IGF-II messenger RNA expression at the CP did not change with age although cerebrospinal fluid (CSF) levels fell. ¹²⁵I-IGF-II uptake in the CP was saturated from either side of the CP, whereas age-related decrease of the uptake was seen at the CSF side but not at the blood side of the CP. The insulin-like growth factor binding protein-2 (IGFBP-2) at 0.01 or 0.1 µg/mL tended to enhance IGF-II uptake at the young CP but not the old CP or other brain tissues, whereas bovine serum albumin generally inhibited the uptake. These age-related changes suggest that the normal autocrine/paracine role of IGF-II at the CP is attenuated with age.

Key Words: Insulin-like growth factor II • Choroid plexus • Aging • Brain • Insulin-like growth factor binding protein-2