French maritime pine bark treatment decelerates plaque development and improves spatial memory in Alzheimer's disease mice

Bibliographic

Year of Publication: 
2019
Contact PI Name: 
Jens Pahnke
Contact PI Affiliation: 
Department of Neuro/Pathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Oslo, Norway
Co-Authors: 
K. Paarmann, S.R. Prakash, M. Krohn, L. Mohle, M. Brackhan, T. Bruning, I. Eiriz
Primary Reference (PubMED ID): 
Funding Source:
Study Goal and Principal Findings: 

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 β-amyloidosis/AD.

Study design/methods: This study experimentally assessed the effects of Pycnogenol on AD-related pathology in a β-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 β-amyloid (Aβ) plaques, number of neurons, glia coverage, myelination pattern, and cortical coverage with axons using immunohistochemistry. As 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 Aβ 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.

Therapeutic Agent

Therapeutic Information: 
Therapy Type:

Animal Model

Model Information: 
Species:
Model Type:
Strain/Genetic Background: 
C57BL/6J

Experimental Design

Is the following information reported in the study?: 
Power/Sample Size Calculation
Blinded for Treatment
Pharmacokinetic Measures
Toxicology Measures
Biomarkers
Formulation
Duration of Treatment
Age of Animal at the Beginning of Treatment
Sex as a Biological Variable
Number of Premature Deaths
Statistical Plan
Inclusion/Exclusion Criteria Included
Randomized into Groups
Blinded for Outcome Measures
Pharmacodynamic Measures
ADME Measures
Dose
Route of Delivery
Frequency of Administration
Age of Animal at the End of Treatment
Study Balanced for Sex as a Biological Variable
Number of Excluded Animals
Genetic Background
Conflict of Interest

Outcomes

Outcomes: 
Outcome MeasuredOutcome Parameters
Behavioral
  • Morris Water Maze
  • Motor Function
  • Locomotor Activity
  • Swimming Speed
  • Histopathology
  • beta Amyloid Deposits
  • beta Amyloid Load
  • Biochemical
  • Brain-Buffer Soluble beta Amyloid Peptide 42
  • Brain-Guanidine Soluble beta Amyloid Peptide 42
  • A Disintegrin and Metalloproteinase Domain 10 (ADAM10)
  • beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)
  • Insulin Degrading Enzyme (IDE)
  • Immunochemistry
  • Amyloid Plaque Size
  • Brain-beta Amyloid Deposits
  • Glial Fibrillary Acidic Protein (GFAP)
  • Ionized Calcium Binding Adaptor Molecule 1 (Iba1)
  • Myelin
  • Myelin Basic Protein
  • Neurofilament
  • Neuronal Marker NeuN
  • Neuronal Nitric Oxide Synthase (nNOS)
  • Synaptophysin
  • Microscopy
  • Cell Count