Nicotinamide Riboside (NR) Supplementation Exerts Neuroprotective Effects in db/db Mouse Model of Type 2 Diabetes

Area of Science:

• Neuroscience
• Metabolic Disorders
• Pharmacology

Background:

• Type 2 diabetes is associated with neuropsychiatric issues like anxiety, impaired brain metabolism, neuroinflammation, and mitochondrial dysfunction.
• Nicotinamide riboside (NR), a precursor to NAD+, shows neuroprotective potential and may help treat these diabetes-related complications.

Purpose of the Study:

• To investigate if NR supplementation can alleviate anxiety-like behavior in a type 2 diabetes mouse model.
• To determine if NR modulates the hippocampal inflammatory response in diabetic mice.

Main Methods:

• Utilized db/db mice (type 2 diabetes model) and db/m mice (controls), divided into four groups.
• Administered NR (500 mg/kg) or control diet for 20 weeks, assessing behavior via open field and nesting tests.
• Conducted biochemical analyses (RT-qPCR, Western blotting, immunohistochemistry) on hippocampal tissues.

Main Results:

• Diabetic db/db mice exhibited increased anxiety and reduced nesting behavior compared to controls.
• NR supplementation ameliorated these anxiety-like behaviors and improved nesting motivation.
• NR treatment reduced hippocampal inflammation, including astrocytosis, microglial activation, STING/NF-kB signaling, and pro-inflammatory cytokines.

Conclusions:

• NR supplementation effectively reduces anxiety-like symptoms and neuroinflammation in diabetic mice.
• NR demonstrates therapeutic potential for mitigating neuropsychiatric complications linked to type 2 diabetes.