title: Protective Effects of Forskolin on Behavioral Deficits and Neuropathological Changes in a Mouse Model of Cerebral Amyloidosis.
abstract: The production of amyloid-β peptides in the brains of patients with Alzheimer disease (AD) may contribute to memory loss and impairments in social behavior. Here, an efficient adenylate cyclase activator, forskolin, was orally administered by gavage (100 mg/kg body weight) to 5-month-old transgenic APP/PS1 mice, which serve as an animal model of cerebral amyloidosis. Analyses of nest construction, sociability, and immunohistochemical features were used to determine the effects of forskolin treatment. After a relatively short term of treatment (10 days), forskolin-treated transgenic mice showed restored nest construction ability (p < 0.05) and their sociability (p < 0.01). There was a reduction of Aβ plaque deposition in the cortex and in the hippocampus. Furthermore, expression of transforming growth factor β, glial fibrillary acidic protein, and Iba-1 in the cortex was reduced in the forskolin-treated group, suggesting regulation of the inflammatory response mediated by activated microglia and astrocytes in the brains of the APP/PS1 mice (p < 0.01). Taken together, these findings suggest that forskolin shows neuroprotective effects in APP/PS1 Tg mice and may be a promising drug in the treatment of patients with AD.
authors.affiliation: From the Division of Immunopathology of the Nervous System, Institute of Pathology and Neuropathology, University of Tubingen, Tubingen, Germany (BAO, CZ, HJS, ZYZ). briceayissi03@yahoo.fr.
authors.forename: Brice Ayissi
authors.initials: BA
authors.lastname: Owona
authors.affiliation: From the Division of Immunopathology of the Nervous System, Institute of Pathology and Neuropathology, University of Tubingen, Tubingen, Germany (BAO, CZ, HJS, ZYZ).
authors.forename: Caroline
authors.initials: C
authors.lastname: Zug
authors.affiliation: From the Division of Immunopathology of the Nervous System, Institute of Pathology and Neuropathology, University of Tubingen, Tubingen, Germany (BAO, CZ, HJS, ZYZ).
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Schluesener
authors.affiliation: From the Division of Immunopathology of the Nervous System, Institute of Pathology and Neuropathology, University of Tubingen, Tubingen, Germany (BAO, CZ, HJS, ZYZ).
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D000818:Animals; D005576:Colforsin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D053764:Presenilin-1 / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D053764:Presenilin-1; D005576:Colforsin
keywords: APP/PS1 transgenic mice; Alzheimer disease; Cerebral amyloidosis; Forskolin.; β-amyloid