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