Reversible inhibition of pyramidal gap junction activity
View Patent ↗The present invention relates to a novel method of inhibiting gap junction-mediated signaling in pyramid cells. Pyramidal gap junctions are quickly and reversibly inhibited by beta-amyloid or biologically active fragments thereof. The present invention also relates to the use of beta-amyloid as an anticonvulsant for the treatment of epilepsy and other pathological hypersynchrony conditions in humans and non-human animals.
1. A method for reducing or inhibiting gap junction-mediated signaling in pyramid cells comprising contacting said cells with beta-amyloid or a gap junction inhibiting fragment thereof and detecting the reduction or inhibition of gap junction-mediated signaling in pyramid cells.
2. A method of inhibiting gap junction-mediated signaling in pyramid cells comprising contacting said cells with a beta-amyloid peptide comprising amino acids 25-35 and detecting the reduction or inhibition of gap junction-mediated signaling in pyramid cells.
3. The method of claim 1 wherein the beta-amyloid is a peptide selected from the group consisting of: beta-amyloid 25-35, beta-amyloid 1-40, and beta-amyloid 1-42.
4. The method of claim 1 or claim 2 wherein the concentration of beta-amyloid is at least 1 nM.
5. A method of therapeutically treating a patient having symptoms of a pathological hypersynchrony condition comprising administering an effective dose of beta-amyloid, wherein said dose of beta-amyloid results in anti-convulsant effects in the patient.
6. The method of claim 5 wherein the patient is a human.
7. The method of claim 5 wherein the patient is a nonhuman animal.
8. The method of claim 5 wherein the condition is epilepsy.
9. The method of any one of claims 5 - 8 , wherein the beta-amyloid is administered orally, subcutaneously, intramuscularly, topically or intravenously.
10. A method of reducing or inhibiting pyramidal cell gap junction activity in a subject, comprising administering to said subject an effective amount of a beta-amyloid peptide, such that pyramidal cell gap junction activity is inhibited, wherein said beta-amyloid peptide is of the formula SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 and wherein the reduction or inhibition of pyramidal cell gap junction activity is detected in the subject.