Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
Open Access
- 18 December 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Neurodegeneration
- Vol. 9 (1), 61
- https://doi.org/10.1186/1750-1326-9-61
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.Keywords
This publication has 71 references indexed in Scilit:
- Biochemistry and Cell Biology of Tau Protein in Neurofibrillary DegenerationCold Spring Harbor Perspectives in Medicine, 2012
- Neurotoxicity of Amyloid -Protein: Synaptic and Network DysfunctionCold Spring Harbor Perspectives in Medicine, 2012
- Deciphering Alzheimer DiseaseCold Spring Harbor Perspectives in Medicine, 2011
- Neuroprotective strategies involving ROS in Alzheimer diseaseFree Radical Biology & Medicine, 2011
- Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapsesProceedings of the National Academy of Sciences of the United States of America, 2010
- Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemiaBritish Journal of Pharmacology, 2010
- Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networksNature Neuroscience, 2010
- Soluble Oligomers of Amyloid β Protein Facilitate Hippocampal Long-Term Depression by Disrupting Neuronal Glutamate UptakeNeuron, 2009
- Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memoryNature Medicine, 2008
- Oxidative damage in Alzheimer'sNature, 1996