Nicotinamide attenuates the decrease in dendritic spine density in hippocampal primary neurons from 5xFAD mice, an...

Area of Science:

• Neuroscience
• Metabolomics
• Biochemistry

Background:

• Alzheimer's disease (AD) is a common neurodegenerative disorder marked by memory loss, amyloid plaques, and neurofibrillary tangles.
• The 5xFAD mouse model exhibits memory deficits and AD-related pathology, making it suitable for investigating disease mechanisms.

Purpose of the Study:

• To investigate metabolic profile alterations in the hippocampus of 5xFAD mice compared to wild-type (WT) mice.
• To explore the potential therapeutic role of nicotinamide in mitigating AD-related neuronal deficits.

Main Methods:

• Untargeted metabolomics profiling of hippocampal tissues from 6, 8, and 12-month-old WT and 5xFAD mice.
• Assessment of nicotinamide's effect on dendritic spine density in hippocampal primary neurons from 5xFAD mice.

Main Results:

• Significantly decreased levels of nicotinamide and adenosine monophosphate were observed in 5xFAD mice hippocampi.
• Elevated levels of lysophosphatidylcholine (LysoPC) and lysophosphatidylethanolamine (LysoPE) were found in 5xFAD mice.
• Nicotinamide treatment attenuated the reduction in dendritic spine density in 5xFAD-derived hippocampal neurons.

Conclusions:

• Reduced hippocampal nicotinamide levels are potentially linked to Alzheimer's disease pathogenesis.
• Nicotinamide replenishment shows promise in ameliorating neuronal deficits associated with AD.
• Nicotinamide represents a potential therapeutic target for Alzheimer's disease.