Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory

Area of Science:

• Neuroscience
• Endocrinology
• Nutritional Science

Background:

• Dietary folate deficiency is linked to cognitive deficits.
• Folate fortification is common, but effects of excess folate during adolescent neurodevelopment are unknown.

Purpose of the Study:

• To investigate the long-term cognitive effects of excess folate supplementation during adolescence.
• To explore potential mechanisms involving thyroid hormone function.

Main Methods:

• Adolescent rats (postnatal days 30-60) were fed diets with high folate (8.0 mg/kg) or control levels (2.7 mg/kg).
• Behavioral tests included the Morris water maze to assess motivation, learning, and spatial memory.
• Molecular analyses examined hippocampal proteins and thyroid hormone levels.

Main Results:

• Folate-supplemented rats showed deficits in motivation and spatial memory.
• No changes were observed in growth-associated protein-43 or Gs-α subunit protein.
• Decreased peripheral thyroxine (T4) and triiodothyronine (T3) levels were noted.
• Reduced hippocampal thyroid receptor-α1 and -α2 (TRα1, TRα2) protein levels were found, potentially due to increased promoter methylation.

Conclusions:

• Adolescent excess folate intake can lead to motivational and spatial memory deficits.
• These deficits may be mediated by suppressed thyroid hormone function.
• Folate supplementation during critical neurodevelopmental periods warrants careful consideration.