RESUMO
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.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Doença de Alzheimer/complicações , Briostatinas/uso terapêutico , Deficiências da Aprendizagem/tratamento farmacológico , Deficiências da Aprendizagem/etiologia , Administração Oral , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Reação de Fuga/efeitos dos fármacos , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Mutação/genética , Presenilina-1/genética , Tempo de Reação/efeitos dos fármacosRESUMO
Fifty-four patients with multiple trauma have been investigated in a prospective one-year documentation. The following features were documented and evaluated: circumstances of the accident, condition on admission, course under special consideration of the cell-mediated immunity with Merieux multitest, course after indoor treatment.
