K Paarmann1, S R Prakash2, M Krohn2, L Möhle3, M Brackhan2, T Brüning2, I Eiriz2, J Pahnke4. 1. Department of Neuro-/Pathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Oslo, Norway; LIED, University of Lübeck, Lübeck, Germany. 2. Department of Neuro-/Pathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Oslo, Norway. 3. Department of Neuro-/Pathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Oslo, Norway; Department for Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Halle, Germany. 4. Department of Neuro-/Pathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Oslo, Norway; LIED, University of Lübeck, Lübeck, Germany; Department for Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Halle, Germany; Department of Pharmacology, Faculty of Medicine, University of Latvia, Rīga, Latvia. Electronic address: jens.pahnke@medisin.uio.no.
Abstract
BACKGROUND: Plant extracts are increasingly investigated as potential drugs against Alzheimer's disease (AD) and dementia in general. Pycnogenol is an extract from the bark of the French maritime pine (Pinus pinaster Aiton subsp. atlantica) with known anti-oxidative and neuroprotective effects. HYPOTHESIS/ PURPOSE: Pycnogenol is thought to improve cognitive functions in elderly. We wanted to investigate and quantify these effects in a model system of cerebral ß-amyloidosis/AD. STUDY DESIGN/ METHODS: This study experimentally assessed the effects of Pycnogenol on AD-related pathology in a ß-amyloidosis mouse model. APP-transgenic mice and controls were treated orally in a pre-onset and post-onset treatment paradigm. The effects of Pycnogenol were characterized by analysing ß-amyloid (Aß) plaques, number of neurons, glia coverage, myelination pattern, and cortical coverage with axons using immunohistochemistry. Aß levels were quantified using ELISA and gene expression levels of APP-processing enzymes ADAM10, BACE1 and IDE protein levels were determined by Western blot. Behavioural changes in circadian rhythm were monitored and spatial memory / cognition was assessed using a water maze test. RESULTS: Pycnogenol significantly decreased the number of plaques in both treatment paradigms but did not alter levels of soluble Aß or the gene expression of APP-processing enzymes. The morphological analyses revealed no changes in the number of neurons, astrocytes, microglia, the myelination pattern, or the morphology of axons. Behavioural testing revealed an improvement of the spatial memory in the pre-onset treatment paradigm only. CONCLUSION: Our results suggest to evaluate clinically a potential use of Pycnogenol in the prevention or in early stages of mild cognitive impairment (MCI) and AD.
BACKGROUND: Plant extracts are increasingly investigated as potential drugs against Alzheimer's disease (AD) and dementia in general. Pycnogenol is an extract from the bark of the French maritime pine (Pinus pinaster Aiton subsp. atlantica) with known anti-oxidative and neuroprotective effects. HYPOTHESIS/ PURPOSE: Pycnogenol is thought to improve cognitive functions in elderly. We wanted to investigate and quantify these effects in a model system of cerebral ß-amyloidosis/AD. STUDY DESIGN/ METHODS: This study experimentally assessed the effects of Pycnogenol on AD-related pathology in a ß-amyloidosis mouse model. APP-transgenic mice and controls were treated orally in a pre-onset and post-onset treatment paradigm. The effects of Pycnogenol were characterized by analysing ß-amyloid (Aß) plaques, number of neurons, glia coverage, myelination pattern, and cortical coverage with axons using immunohistochemistry. Aß levels were quantified using ELISA and gene expression levels of APP-processing enzymes ADAM10, BACE1 and IDE protein levels were determined by Western blot. Behavioural changes in circadian rhythm were monitored and spatial memory / cognition was assessed using a water maze test. RESULTS: Pycnogenol significantly decreased the number of plaques in both treatment paradigms but did not alter levels of soluble Aß or the gene expression of APP-processing enzymes. The morphological analyses revealed no changes in the number of neurons, astrocytes, microglia, the myelination pattern, or the morphology of axons. Behavioural testing revealed an improvement of the spatial memory in the pre-onset treatment paradigm only. CONCLUSION: Our results suggest to evaluate clinically a potential use of Pycnogenol in the prevention or in early stages of mild cognitive impairment (MCI) and AD.