Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Area of Science:

• Neuroscience
• Cell Biology
• Nutritional Science

Background:

• Selenium is vital for brain function, transported by selenoprotein P (SEPP1) via its receptor LRP8 at the blood-brain barrier.
• Genetic deletion of SEPP1 or LRP8 causes severe neurological issues in selenium-deficient mice.
• Previous research indicates residual motor and cognitive deficits in mice on standard diets after SEPP1 or LRP8 deletion.

Purpose of the Study:

• To directly compare the motor and cognitive performance of Sepp1 and Lrp8 knockout mice on a standard diet.
• To elucidate the specific roles of SEPP1 and LRP8 in maintaining brain function under normal dietary conditions.

Main Methods:

• Comparative analysis of motor function, spatial learning, and memory in Sepp1 and Lrp8 knockout mice versus wild-type littermates.
• Mice were fed a standard chow diet throughout the study.
• Assessment of adult hippocampal neurogenesis in Lrp8-deficient mice and the effect of selenium supplementation.

Main Results:

• Sepp1 knockout mice on a selenium-replete diet exhibited normal motor and cognitive functions, indistinguishable from wild-type controls.
• Lrp8 knockout mice on a selenium-replete diet displayed normal motor function but showed subtle deficits in spatial learning and memory.
• Dietary selenium supplementation did not rescue the impaired adult hippocampal neurogenesis observed in Lrp8-deficient mice.

Conclusions:

• SEPP1 plays a role in brain function that is compensated for on a standard diet, while LRP8 is critical for spatial learning and memory, independent of dietary selenium levels.
• These findings underscore the essential role of selenium transport mechanisms, particularly LRP8, in maintaining specific cognitive functions within the brain.
• The inability to rescue neurogenesis deficits in Lrp8-deficient mice suggests LRP8's role extends beyond simple selenium delivery.