Complementary remedy of aged-related learning and memory deficits via exogenous choline acetyltransferase.
The present study aimed to examine whether the aged mice with naturally occurring cognitive deficits in learning and memory would benefit from supplementation of choline acetyltransferase (ChAT), the biosynthetic enzyme for neurotransmitter acetylcholine. Delivered by protein transduction domain (PTD), ChAT could pass through the blood-brain barrier, enter the neurons, interact with heat shock protein 70kDa, and retain enzyme activity. In behavior tests, PTD-ChAT given to the aged and memory-deficient mice almost completely reversed the behavioral changes, such as impairment of memory retention in the step-through test (an index of long-term memory) and prolonged swimming time in water maze test (an index of spatial recognition memory). The results suggest a novel and potential therapeutic use of PTD-ChAT in the age-related cognitive deficits.
Fu
Ai Ling
AL
Department of Biochemistry and Pharmacology, Institute of Pharmacology and Toxicology, Beijing 100850, China. A.L.Fu@hotmail.com
Huang
Shi Jie
SJ
Sun
Man Ji
MJ
D000375:Aging; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D002795:Choline O-Acetyltransferase / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007859:Learning Disabilities / Q000188:drug therapy*; D018782:Maze Learning; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D011994:Recombinant Proteins; D002795:Choline O-Acetyltransferase