Disruption of the sodium-dependent citrate transporter SLC13A5 in mice causes alterations in brain citrate levels and neuronal network excitability in the hippocampus.

Disruption of the sodium-dependent citrate transporter SLC13A5 in mice causes alterations in brain citrate levels and neuronal network excitability in the hippocampus. Neurobiol Dis. 2020 Jul 16;:105018 Authors: Henke C, Töllner K, van Dijk RM, Miljanovic N, Cordes T, Twele F, Bröer S, Ziesak V, Rohde M, Hauck SM, Vogel C, Welzel L, Schumann T, Willmes DM, Kurzbach A, El-Agroudy NN, Bornstein SR, Schneider SA, Jordan J, Potschka H, Metallo CM, Köhling R, Birkenfeld AL, Löscher W Abstract In addition to tissues such as liver, the plasma membrane sodium-dependent citrate transporter, NaCT (SLC13A5), is highly expressed in brain neurons, but its function is not understood. Loss-of-function mutations in the human SLC13A5 gene have been associated with severe neonatal encephalopathy and pharmacoresistant seizures. The molecular mechanisms of these neurological alterations are not clear. We performed a detailed examination of a Slc13a5 deletion mouse model including video-EEG monitoring, behavioral tests, and electrophysiologic, proteomic, and metabolomic analyses of brain and cerebrospinal fluid. The experiments revealed an increased propensity for epileptic seizures, proepileptogenic neuronal excitability changes in the hippocampus, and significant citrate alterations in the CSF and brain tissue of Slc13a5 deficient mice, which may underlie the neurological abnormalities. These data demonstrate that SLC13A5 is involved in brain citra...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research