title: Acute oral Bryostatin-1 administration improves learning deficits in the APP/PS1 transgenic mouse model of Alzheimer's disease.
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.
authors.forename: L M
authors.initials: LM
authors.lastname: Schrott
authors.forename: K
authors.initials: K
authors.lastname: Jackson
authors.forename: P
authors.initials: P
authors.lastname: Yi
authors.forename: F
authors.initials: F
authors.lastname: Dietz
authors.forename: G S
authors.initials: GS
authors.lastname: Johnson
authors.forename: T F
authors.initials: TF
authors.lastname: Basting
authors.forename: G
authors.initials: G
authors.lastname: Purdum
authors.forename: T
authors.initials: T
authors.lastname: Tyler
authors.forename: J D
authors.initials: JD
authors.lastname: Rios
authors.forename: T P
authors.initials: TP
authors.lastname: Castor
authors.affiliation: Molecular / Cellular Physiology / Medicine, LSU Health - Shreveport, 1501 Kings Highway, Shreveport, LA 71130-3932, USA. jalexa@lsuhsc.edu.
authors.forename: J S
authors.initials: JS
authors.lastname: Alexander
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000284:Administration, Oral; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D054713:Bryostatins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects; D006801:Humans; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D011930:Reaction Time / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D016564:Amyloid beta-Protein Precursor; D054713:Bryostatins; C508853:PSEN1 protein, human; D053764:Presenilin-1; C046785:bryostatin 1