TY - JOUR
T1 - Neurophysiologic effects of folate compounds in hippocampus, in vitro
AU - Clifford, David B.
AU - Ferrendelli, James A.
PY - 1983/5/5
Y1 - 1983/5/5
N2 - Pteroylglutamic acid (PGA, folic acid) and related compounds were studied for their electropysiologic effects on guinea pig hippocampal slices in vitro. Folates are found to have marked neuroexcitatory actions in CA3 and lesser but substantial excitatory effects in CA1. The dentate gyrus is minimally activated by folates. Extracellular recordings in CA3 reveal augmentation in single unit activity, evoked responses, and at 50-100 μM PGA concentrations, spontaneous epileptiform discharges are generated. Progressive increase in PGA concentrations to at least 2 mM do not result in loss of this activity. At concentrations of 200 μM, epileptiform bursts in CA3, precede those in CA1 which are lost by sectioning the Schaeffer collateral pathway. However, with 500 μM PGA, spontaneous bursts occur in CA1 isolated from CA3. The change induced by PGA primarily affects the population spike resulting in lower stimulus threshold and higher amplitude response. Measurement of threshold concentration necessary to produce spontaneous epileptiform activity of folate related compounds reveals the following order of potency: pteroylglutamic acid (PGA) ≥ formyl tetrahydrofolic acid (folinic acid) > > methyltetrahydrofolate (MTHF) ≥ methotrexate (MTX) ≥ glutamic acid. Pteroic acid, pterin, N(p-aminobenzoyl) L-glutamic acid are inactive. Methotrexate does not diminish the response to PGA. Thus, the entire folate molecule is needed for full activity. Folates represent naturally occurring, highly epileptogenic compounds whose mechanism of action is not dependent on metabolic products. Possibly they act at a central receptor as a neuromodulator.
AB - Pteroylglutamic acid (PGA, folic acid) and related compounds were studied for their electropysiologic effects on guinea pig hippocampal slices in vitro. Folates are found to have marked neuroexcitatory actions in CA3 and lesser but substantial excitatory effects in CA1. The dentate gyrus is minimally activated by folates. Extracellular recordings in CA3 reveal augmentation in single unit activity, evoked responses, and at 50-100 μM PGA concentrations, spontaneous epileptiform discharges are generated. Progressive increase in PGA concentrations to at least 2 mM do not result in loss of this activity. At concentrations of 200 μM, epileptiform bursts in CA3, precede those in CA1 which are lost by sectioning the Schaeffer collateral pathway. However, with 500 μM PGA, spontaneous bursts occur in CA1 isolated from CA3. The change induced by PGA primarily affects the population spike resulting in lower stimulus threshold and higher amplitude response. Measurement of threshold concentration necessary to produce spontaneous epileptiform activity of folate related compounds reveals the following order of potency: pteroylglutamic acid (PGA) ≥ formyl tetrahydrofolic acid (folinic acid) > > methyltetrahydrofolate (MTHF) ≥ methotrexate (MTX) ≥ glutamic acid. Pteroic acid, pterin, N(p-aminobenzoyl) L-glutamic acid are inactive. Methotrexate does not diminish the response to PGA. Thus, the entire folate molecule is needed for full activity. Folates represent naturally occurring, highly epileptogenic compounds whose mechanism of action is not dependent on metabolic products. Possibly they act at a central receptor as a neuromodulator.
KW - epilepsy
KW - folate compounds
KW - folic acid
KW - hippocampal slices
KW - kainic acid
UR - http://www.scopus.com/inward/record.url?scp=0020640268&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(83)90651-0
DO - 10.1016/0006-8993(83)90651-0
M3 - Article
C2 - 6871658
AN - SCOPUS:0020640268
SN - 0006-8993
VL - 266
SP - 209
EP - 216
JO - Brain Research
JF - Brain Research
IS - 2
ER -