Skip to main content
U.S. flag

An official website of the United States government

All-trans retinoic acid improved impaired proliferation of neural stem cells and suppressed microglial activation in the hippocampus in an Alzheimer’s mouse model

Bibliographic

Year of Publication:
2017
Contact PI Name:
Toshio Ohshima
Contact PI Affiliation:
Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan
Co-Authors:
Risa Takamura, Naoto Watamura, Miyu Nikkuni
Primary Reference (PubMED ID):
Funding Source:
Not Reported
Study Goal and Principal Findings:

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by cognitive impairment with neuronal loss. The number of patients suffering from AD has increased, but none of the present therapies stops the progressive symptoms in patients with AD. It has been reported that the activation of microglial cells induces harmful chronic inflammation, leading to neuronal death. Furthermore, the impairment of adult neurogenesis in the hippocampus has been observed earlier than amyloid plaque formation. Inflammatory response may lead to impaired adult neurogenesis in patients with AD. This study examines the relationship between adult neurogenesis and neuroinflammation using APPswe/ PS1M146V/tauP301L (33Tg) mice. They observed a decline in the proliferation of neural stem cells and the occurrence of severe inflammation in the hippocampus of 33Tg mouse brains at 12 months of age. Previously, there research had shown an anti-inflammatory effect of all-trans retinoic acid (ATRA) in the 33Tg mouse brain. They found that ATRA has effects on the recovery of proliferative cells along with suppression of activated microglia in the hippocampus. These results suggest that the inhibition of microglial activation by ATRA leads to recovery of adult neurogenesis in the hippocampus in an AD mouse model.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
All-trans Retinoic Acid (ATRA)
Therapeutic Target:
Retinoic Acid Receptors

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1xTau
Strain/Genetic Background:
Not Reported

Experimental Design

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

Outcomes

Outcome Measured
Outcome Parameters
Histopathology
Activated Microglia
Activated Astrocytes
Immunochemistry
Ionized Calcium Binding Adaptor Molecule 1 (Iba1)
Glial Fibrillary Acidic Protein (GFAP)
Cell Proliferation