DMSO modulates CNS function in a preclinical Alzheimer's disease model

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Dimethyl sulfoxide (DMSO) is widely used as a vehicle for drug delivery.
• Its potential pharmacological effects on the central nervous system (CNS) are not well understood.
• Alzheimer's disease (AD) is characterized by synaptic dysfunction and cognitive decline.

Purpose of the Study:

• To investigate the effects of chronic low-dose DMSO on brain structure and function.
• To examine DMSO's impact on synaptic connectivity and behavior in a preclinical model of AD (APP_SDL mice).
• To explore the mechanisms underlying DMSO's potential therapeutic effects.

Main Methods:

• Chronic administration of low-dose DMSO to APP_SDL mice.
• Ex vivo and in vivo analysis of hippocampal spine density.
• Behavioral testing including spatial memory, olfactory habituation, and anxiety-like behavior.
• Assessment of amyloid-beta (Aβ) oligomer levels.
• Experiments using organotypic hippocampal slice cultures challenged with NMDA receptor antagonists (MK-801).

Main Results:

• DMSO treatment significantly increased hippocampal spine density in APP_SDL mice.
• DMSO administration improved spatial memory accuracy and olfactory habituation, and exhibited anxiolytic effects.
• DMSO's beneficial effects were observed in the presence of elevated Aβ levels but did not involve a reduction in Aβ oligomers.
• Experiments with MK-801 suggested DMSO modulates NMDA receptor signaling pathways influencing spine density.

Conclusions:

• DMSO acts as a bioactive compound with significant CNS effects.
• DMSO demonstrates potential as an adjuvant therapy to mitigate Aβ-mediated synaptotoxicity and cognitive impairments in AD.
• Further research is warranted to elucidate the full therapeutic potential of DMSO in neurological disorders.