title: Dietary folic acid intake differentially affects methionine metabolism markers and hippocampus morphology in aged rats.
abstract: OBJECTIVE
  Folic acid (FA) is an emerging nutritional factor in the pathogenesis of diverse neurodegenerative disorders by still unknown mechanisms. The hippocampus is altered during the loss of cognitive abilities in humans and selectively affected when homocysteine increases. The aim was to evaluate the potential protective role of folic acid in the maintenance of biochemical markers related to the methionine cycle, as well as the integrity of the hippocampus as part of the brain in aged rats.
  
  
  METHODS
  Male Sprague-Dawley rats (18 months old) were assigned to four different folic acid groups (0 mg FA/kg diet, deficient; 2 mg FA/kg diet, control; 8 mg FA/kg diet, moderate supplementation; 40 mg FA/kg diet, extra supplementation) for 30 days. We evaluated several parameters related to the methionine cycle. In addition, hippocampus areas were immunostained for specific neuronal markers and astrocytes.
  
  
  RESULTS
  Serum folate levels increased according to FA dietary level (p < 0.01). There was a significant increase in the serum homocysteine concentrations in the folic acid-deficient diet group (p < 0.01). However, brain S-adenosylmethionine and S-adenosylhomocysteine did not differ significantly between the folic acid groups. Consequently, the methylation ratio was also unchanged. The morphometric analysis did not show any differences in the number of neurons and astrocytes between groups, except when comparing the folic acid-deficient diet versus folic acid-supplemented diet in the striatum of the hippocampus.
  
  
  CONCLUSIONS
  Clearly, the dietary FA deficiency negatively affects the methionine metabolism biomarkers, while excessive supplementation seems to be unnecessary for optimal maintenance of the methylation cycle and hippocampus integrity.
authors: Departamento de Ciencias Farmacéuticas y de la Alimentación, Facultad de Farmacia, San Pablo CEU University, Madrid, Spain.
authors: Teresa
authors: T
authors: Partearroyo
authors: Julia
authors: J
authors: Pérez-Miguelsanz
authors: Natalia
authors: N
authors: Úbeda
authors: María
authors: M
authors: Valencia-Benítez
authors: Elena
authors: E
authors: Alonso-Aperte
authors: Gregorio
authors: G
authors: Varela-Moreiras
mesh_terms: D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D005494:Folic Acid Deficiency / Q000178:diet therapy / Q000209:etiology / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D020138:Hyperhomocysteinemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008745:Methylation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D008715:Methionine