Lactate receptor HCAR1 in neonatal hypoxic-ischemic seizures

Hydroxycarboxylic acid receptor 1 (HCAR1) is a G-protein-coupled lactate receptor expressed in the brain and plays a role in neuronal excitability and repair after injury. Hypoxic-ischemic encephalopathy (HIE) is the most common cause of brain injury and seizures in term neonates. The goal of this study was to describe HCAR1 expression and function in the neonatal brain and understand its role in HIE-associated seizures. HCAR1 expression was measured using quantitative reverse transcriptase polymerase chain reaction in postnatal day (p)10-50 mice. Neuronal properties and spontaneous excitatory postsynaptic currents (sEPSCs) were measured in hippocampal principal neurons from HCAR1 knockout and wild-type mice when exposed to lactate. p10 HCAR1 knockout and wild-type mice were exposed to hypoxia-ischemia (HI) and underwent electroencephalography to compare seizure burden. HCAR1 was expressed at p10 at similar levels to adults. Lactate decreased amplitudes and sEPSC frequency in wild-type but not HCAR1 knockout mice. After HI, HCAR1 knockout mice had higher seizure burden and behavioral seizure scores than wild-type mice. HCAR1 is expressed on neurons and plays a role in neuronal excitability and seizures in the neonatal brain.