Elke Edelmann, Germany
Institute of Physiology Medical Faculty, Otto-von-Guericke UniversityAuthor Of 1 Presentation
ANTI-INFLAMMATORY TREATMENT WITH FTY720 STARTING AFTER ONSET OF DISEASE SYMPTOMS REVERSES SYNAPTIC DEFICITS IN AN APP/PS1 MOUSE MODEL
Abstract
Aims
The identification of an effective medication for patients with Alzheimer’s disease (AD) given after disease onset remains one of the most challenging topics in neuroscience research. In this study, we investigated whether the FDA approved drug fingolimod (FTY720) can rescue AD-associated synaptic and memory impairments in an AD mouse model when treatment starts after onset of symptoms.
Methods
Male APP/PS1 mice were intraperitoneally injected every second day with FTY720 for 1-2 months starting at the age of 5-6 months. We conducted Golgi-Cox staining combined with fluorescent labeling of amyloid plaques and long-term potentiation (LTP) recordings for performing structural and synaptic analysis respectively in treated and untreated animals. Furthermore, we tested spatial memory performance through the Morris water maze task and investigated the levels of neuroinflammation and amyloid beta accumulation in AD mice observed in response to FTY720 treatment.
Results
FTY720 rescued spine and LTP deficits in hippocampal CA1 pyramidal neurons and ameliorated hippocampus-dependent memory dysfunctions observed in untreated APP/PS1 animals at the age of 6-7 months. We also found that our FTY720 treatment regime strongly down-regulated neuroinflammation in hippocampus and neocortex, accompanied by a moderate reduction of amyloid beta deposition in the same brain areas.
Conclusions
Our results demonstrate a beneficial effect of FTY720, when applied after onset of disease symptoms in APP/PS1 mice, and suggest that our treatment regime rescues synaptic and memory deficits observed in untreated AD mice through anti-neuroinflammatory actions of the drug on brain immune cells.