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Acute Oral Bryostatin-1 Administration Improves Learning Deficits in the APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease

[ Vol. 12 , Issue. 1 ]

Author(s):

L.M. Schrott, K. Jackson, P. Yi, F. Dietz, G.S. Johnson, T.F. Basting, G. Purdum, T. Tyler, J.D. Rios, T.P. Castor and J.S. Alexander   Pages 22 - 31 ( 10 )

Abstract:


Background: Previous studies showed that Bryostatin-1, a potent PKC modulator and alphasecretase activator, can improve cognition in models of Alzheimer’s disease (AD) with chronic (>10 weeks), intraperitoneal (i.p.) administration of the drug. We compared learning and spatial memory in the APPswe, PSEN1dE985Dbo (APP/PS1) mouse model of AD and studied the ability of acute intraperitoneal and oral Bryostatin-1 to reverse cognitive deficits in this model. Compared to wild-type (WT) mice, APP/PS1 mice showed significant delays in learning the location of a submerged platform in the Morris water maze. Bryostatin-1 was administered over a 2-week course prior to and during water maze testing. Results: Acute i.p. Bryostatin-1 administration did not improve latency to escape but oral Bryostatin-1 significantly improved memory (measured by a reduction in latency to escape). This benefit of oral Bryostatin-1 administration was most apparent during the first 3 days of testing. These findings show that: 1) Bryostatin-1 is orally active in models of learning and memory, 2) this effect can be produced in less than 2 weeks and 3) this effect is not seen with i.p. administration. We conclude that oral Bryostatin-1 represents a novel, potent and long-acting memory enhancer with future clinical applications in the treatment of human AD.

Keywords:

Amyloid-beta, aging, bryoids, water maze, memory, hippocampus.

Affiliation:

Molecular / Cellular Physiology / Medicine, LSU Health - Shreveport, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.



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