TY - JOUR
T1 - Folate homeostasis in epileptic rats
AU - Mann, Aniv
AU - Portnoy, Emma
AU - Han, Hadas
AU - Inbar, Dorrit
AU - Blatch, Dana
AU - Shmuel, Miriam
AU - Ben-Hur, Tamir
AU - Eyal, Sara
AU - Ekstein, Dana
N1 - Publisher Copyright:
© 2018
PY - 2018/5
Y1 - 2018/5
N2 - Folate is involved in metabolic processes and it has been implicated in both aggravation and amelioration of seizures. The aim of the current work was to study the effect of chronic temporal lobe epilepsy (TLE) on the plasma and brain concentrations of folate and on its uptake carriers in the brain − the reduced folate carrier (RFC), folate receptor α (FRα) and proton coupled folate transporter (PCFT). We utilized the rat lithium pilocarpine model for TLE. Approximately two months following status epilepticus, rats with spontaneous recurrent seizures (SRS) were sacrificed for brain and plasma folate concentration analyses and folate uptake carrier expression studies. RT-PCR and western blot analyses were utilized for quantification of folate carriers’ mRNAs and proteins, respectively. The distribution of folate carriers in the brain was studied using immunohistochemistry. In the SRS rats we found lower plasma concentrations (10 ± 0.9 in control vs. 6.6 ± 1.6 ng/ml in SRS, P < 0.05), but preserved cortical and increased hippocampal levels of folate (0.5 ± 0.1 in control vs. 0.9 ± 0.2 ng/mg in SRS, P = 0.055). Hippocampus - to - plasma ratio of folate concentration was 3-fold higher in the SRS group, compared with the controls (0.13 ± 0.03 vs. 0.04 ± 0.02, respectively; P < 0.01). mRNA and protein levels of the folate uptake carriers did not differ between SRS rats and controls. However, immunofluorescent staining quantification revealed that the emission intensity of both RFC and FRα was elevated 8-fold and 4-fold, respectively, in hippocampal CA1 neurons of SRS rats, compared to controls (P < 0.01). PCFT was unquantifiable. If corroborated by complementary research in humans, the findings of this study may be utilized clinically for supplemental therapy planning, in imaging the epileptic focus, and for drug delivery into the epileptic brain. Further studies are required for better elucidating the clinical and mechanistic significance of altered folate balances in the epileptic brain.
AB - Folate is involved in metabolic processes and it has been implicated in both aggravation and amelioration of seizures. The aim of the current work was to study the effect of chronic temporal lobe epilepsy (TLE) on the plasma and brain concentrations of folate and on its uptake carriers in the brain − the reduced folate carrier (RFC), folate receptor α (FRα) and proton coupled folate transporter (PCFT). We utilized the rat lithium pilocarpine model for TLE. Approximately two months following status epilepticus, rats with spontaneous recurrent seizures (SRS) were sacrificed for brain and plasma folate concentration analyses and folate uptake carrier expression studies. RT-PCR and western blot analyses were utilized for quantification of folate carriers’ mRNAs and proteins, respectively. The distribution of folate carriers in the brain was studied using immunohistochemistry. In the SRS rats we found lower plasma concentrations (10 ± 0.9 in control vs. 6.6 ± 1.6 ng/ml in SRS, P < 0.05), but preserved cortical and increased hippocampal levels of folate (0.5 ± 0.1 in control vs. 0.9 ± 0.2 ng/mg in SRS, P = 0.055). Hippocampus - to - plasma ratio of folate concentration was 3-fold higher in the SRS group, compared with the controls (0.13 ± 0.03 vs. 0.04 ± 0.02, respectively; P < 0.01). mRNA and protein levels of the folate uptake carriers did not differ between SRS rats and controls. However, immunofluorescent staining quantification revealed that the emission intensity of both RFC and FRα was elevated 8-fold and 4-fold, respectively, in hippocampal CA1 neurons of SRS rats, compared to controls (P < 0.01). PCFT was unquantifiable. If corroborated by complementary research in humans, the findings of this study may be utilized clinically for supplemental therapy planning, in imaging the epileptic focus, and for drug delivery into the epileptic brain. Further studies are required for better elucidating the clinical and mechanistic significance of altered folate balances in the epileptic brain.
KW - Cornu Ammonis 1 (CA1)
KW - Folate receptor alpha
KW - Folic acid
KW - Reduced folate carrier
KW - Spontaneous recurrent seizures
KW - Temporal lobe epilepsy
UR - http://www.scopus.com/inward/record.url?scp=85044089349&partnerID=8YFLogxK
U2 - 10.1016/j.eplepsyres.2018.03.014
DO - 10.1016/j.eplepsyres.2018.03.014
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C2 - 29571151
AN - SCOPUS:85044089349
SN - 0920-1211
VL - 142
SP - 64
EP - 72
JO - Epilepsy Research
JF - Epilepsy Research
ER -