title: Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aβ oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3β (GSK-3β). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AβPPswe/PS-1 Alzheimer's model. ANDRO reduces the Aβ levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aβ oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression.
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE), Santiago, Chile. faserran@uc.cl.
authors.forename: Felipe G
authors.initials: FG
authors.lastname: Serrano
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE), Santiago, Chile. cheril.tapia@gmail.com.
authors.forename: Cheril
authors.initials: C
authors.lastname: Tapia-Rojas
authors.affiliation: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. fvcarvajal@uc.cl.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Carvajal
authors.affiliation: Instituto de Farmacología y Morfofisiología, Universidad Austral de Chile, Valdivia, Chile. jhanckeo@gmail.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Hancke
authors.affiliation: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. wcerpa@bio.puc.cl.
authors.forename: Waldo
authors.initials: W
authors.lastname: Cerpa
authors.affiliation: Centro de Envejecimiento y Regeneración (CARE), Santiago, Chile. ninestrosa@bio.puc.cl.|Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. ninestrosa@bio.puc.cl.|Center of Healthy Brain Aging, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia. ninestrosa@bio.puc.cl.|Centro UC Síndrome de Down, Pontificia Universidad Católica de Chile, Santiago, Chile. ninestrosa@bio.puc.cl.|Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile. ninestrosa@bio.puc.cl.|CARE Biomedical Center, P. Catholic University of Chile, Postal code 8331150, PO Box 114-D, Santiago, Chile. ninestrosa@bio.puc.cl.
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003072:Cognition Disorders / Q000473:pathology*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; C030419:andrographolide