Reelin rescues congnitive function
Disclosed are methods of influencing, and enhancing, cognitive function by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.
1. A method of improving associative learning and spatial learning and long term potentiation of neurons in a subject, comprising the step of administering a therapeutically effective amount of a 180 kDa Reelin protein fragment or a 370 kDa Reelin protein fragment to the subject;
where the improvement in associative learning and spatial learning is between 20% and 400% improvement and improvement in long term potentiation is between 20% and 46%; and
wherein the 180 kDa Reelin protein fragment or the 370 kDa Reelin protein fragment is administered into the ventricles of the subject.
2. The method of claim 1 , wherein the therapeutically effective amount of the 180 kDa Reelin protein fragment or the 370 kDa Reelin protein fragment is about 5 nM.