Amprolium exposure alters mice behavior and metabolism in vivo

Area of Science:

• Neuroscience
• Biochemistry
• Animal Models

Background:

• Established thiamine deficiency (TD) models primarily utilize pyrithiamine, with limited use of other analogs in rodents.
• Investigating novel thiamine analogs for TD modeling is crucial for understanding deficiency mechanisms.
• Amprolium, a thiamine analog, has not been extensively studied for inducing TD in rodent models.

Purpose of the Study:

• To evaluate the effects and mechanisms of amprolium-induced thiamine deficiency (TD) in mice via intraperitoneal injection.
• To assess the potential of antioxidant and anti-inflammatory compounds (Trolox, DMSO) in mitigating amprolium-induced TD pathogenesis.

Main Methods:

• Male mice were divided into control and thiamine-deficient (TD) groups, fed standard or TD diets for 20 days.
• Control and TD groups received intraperitoneal injections of saline, Trolox, or DMSO.
• Behavioral tests were conducted, followed by post-mortem analysis of brain and visceral tissues.

Main Results:

• Amprolium exposure led to significant weight loss, hyporexia, and impaired behavioral parameters (locomotion, exploration, motor coordination).
• Cerebral and hepatic changes included reduced cortical cell viability and liver steatosis, respectively.
• Trolox partially ameliorated amprolium-induced effects, while DMSO demonstrated a more pronounced protective effect.

Conclusions:

• Amprolium-induced TD offers a potentially valuable model due to its slower onset and milder progression.
• The findings suggest that amprolium-induced TD involves significant oxidative stress and inflammation.
• Oxidative stress and inflammation are implicated as primary drivers of cellular dysfunction in this TD model.