Folic acid, but not folate, regulates different stages of neurogenesis in the ventral hippocampus of adult female rats.

Folate is an important regulator of hippocampal neurogenesis, and folic acid is needed prenatally to reduce the risk of neural tube defects. Both high levels of folic acid and low levels of folate can be harmful to health because low levels of folate have been linked to several diseases while high folic acid supplements can mask a vitamin B12 deficiency. Depressed patients exhibit folate deficiencies, lower levels of hippocampal neurogenesis, elevated levels of homocysteine and elevated levels of the stress hormone, cortisol, which may be inter-related. In the present study, we were interested in whether different doses of natural folate or synthetic folic acid diets can influence neurogenesis in the hippocampus, levels of plasma homocysteine and serum corticosterone in adult female rats. Adult female Sprague-Dawley rats underwent dietary interventions for 29 days. Animals were randomly assigned to six different dietary groups: folate deficient + succinylsulphathiazole (SST), low 5-methyltetrahydrofolate (5-MTHF), low 5-MTHF + (SST), high 5-MTHF + SST, low folic acid and high folic acid. SST was added to a subset of the 5-MTHF diets to eliminate folic acid production in the gut. Before and after dietary treatment, blood samples were collected for corticosterone and homocysteine analysis, and brain tissue was collected for neurogenesis analysis. High folic acid and low 5-MTHF without SST increased the number of immature neurones (doublecortin-expressing cells) within the ventral hippocampus compared to folate deficient controls. Low 5-MTHF without SST significantly increased the number of immature neurones compared to low and high 5-MTHF + SST, indicating that SST interfered with elevations in neurogenesis. Low folic acid and high 5-MTHF + SST reduced plasma homocysteine levels compared to controls, although there was no significant effect of diet on serum corticosterone levels. In addition, low folic acid and high 5-MTHF + SST reduced the number of mature new neurones in the ventral hippocampus (bromodeoxyuridine/NeuN-positive cells) compared to folate deficient controls. Overall, folic acid dose-dependently influenced neurogenesis with low levels decreasing but high levels increasing neurogenesis in the ventral hippocampus, suggesting that this region, which is important for regulating stress, is particularly sensitive to folic acid in diets. Furthermore, the addition of SST negated the effects of 5-MTHF to increase neurogenesis in the ventral hippocampus.

Prolonged induction of germfree bile acid pattern in conventional rats by antibiotics.

Male conventional rats have been treated for five days with benzylpenicillin, neomycin, kanamycin, erythromycin, bacitracintneomycin, succihylsulfathiazole or metronidazole. Total fecal bile acids were analyzed in samples collected during periods of three days during the pretreatment period and during the eight weeks following drug treatment. Metronidazole or succinylsulfathiazole had no or minor effects on the conventional bile acid pattern and the "bile acid index" (ratio beta-muricholic acid/deoxycholic acid) remained low. Benzylpenicillin, neomycin or kanamycin induced a germfree bile acid pattern, i.e. increased the relative amounts of alpha-and beta-muricholic acid in feces and eliminated deoxycholic acid and hyodeoxycholic acid from feces. The high bile acid index was normalized within three weeks after termination of drug treatment but the excretion of alpha- and beta-muricholic acid was not normalized until a normal flora had been established by giving an enema with intestinal contents from intact, oncentional rats. Treatment with eythromycin or bacitracintineomycin also produced a germfree bile acid pattern. In these cases, the bile acid index was not back to normal until after five to eight weeks and the excretion of the muricholic acids was not normalized until an enema with intestinal bacteria had been given. It is suggested that these long-lasting effects of antibiotics on the metabolism of bile acids in the intestinal tract should be considered after short-term antibiotic therapy in humans.