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3,6'-Dithiothalidomide, a new TNF-α synthesis inhibitor, attenuates the effect of Aβ1-42 intracerebroventricular injection on hippocampal neurogenesis and memory deficit


Year of Publication:
Contact PI Name:
Isabella Russo
Contact PI Affiliation:
Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, Bethesda, Maryland, USA
Luca Caracciolo, David Tweedie, Sang-Ho Choia, Nigel H. Greig, Sergio Barlati, Francesca Bosetti
Primary Reference (PubMED ID):
Funding Source:
Intramural Research Program of the National Institute on Aging
NEDD Project Regione Lombardia
National Institutes of Health (NIH)
Study Goal and Principal Findings:

In this study the authors investigated the effects of a novel thalidomide-based TNF-α lowering drug, 3,6′-dithiothalidomide, on hippocampal progenitor cell proliferation, neurogenesis and memory tasks after intracerebroventricular (i.c.v.) injection of β-amyloid (Aß)1-42 peptide. Seven days after Aβ1-42 injection, a significant proliferation of hippocampal progenitor cells and memory impairment were evident. Four weeks after Aβ1–42 peptide injection, elevated numbers of surviving BrdU cells and newly formed neurons were detected. Treatment with 3,6′-dithiothalidomide attenuated these Aβ1-42 provoked effects. The data indicate that although treatment with 3,6′-dithiothalidomide in part attenuated the increase in hippocampal neurogenesis caused by Aβ1-42-induced neuroinflammation, the drug prevented memory deficits associated with increased numbers of activated microglial cells and inflammatory response. In conclusion, the data indicate that TNF-α synthesis inhibition by 3,6′-dithiothalidomide treatment prevents memory impairments induced by a Aβ1-42-neuroinflammation and suggest that this drug should be further investigated as a therapeutic in AD as well as other animal models of neurodegenerative disease with an inflammatory component.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Tumor Necrosis Factor alpha (TNF alpha)

Animal Model

Model Information:
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:

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
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


Outcome Measured
Outcome Parameters
Morris Water Maze
Tumor Necrosis Factor alpha (TNF alpha)
Activated Microglia
Granular Cell Differentiation
Cell Survival