title: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice.
abstract: Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 microm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 microm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.
authors.affiliation: Aragon Science, Leominster, MA 01453, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Serra
authors.forename: Amy
authors.initials: A
authors.lastname: Chan
authors.forename: Maya
authors.initials: M
authors.lastname: Dubey
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gilman
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D012436:S-Adenosylmethionine; D005492:Folic Acid; D000109:Acetylcholine