Lactate receptor HCAR1 in neonatal hypoxic-ischemic seizures

Area of Science:

• Neuroscience
• Neonatal Research
• Molecular Biology

Background:

• Hydroxycarboxylic acid receptor 1 (HCAR1) is a G-protein-coupled receptor activated by lactate.
• HCAR1 is expressed in the brain and implicated in neuronal function and injury repair.
• Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal brain injury and seizures.

Purpose of the Study:

• To investigate HCAR1 expression and function in the developing neonatal brain.
• To determine the role of HCAR1 in seizures associated with HIE.

Main Methods:

• Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) for HCAR1 expression analysis in mouse brains (postnatal days 10-50).
• Electrophysiological recordings of neuronal properties and spontaneous excitatory postsynaptic currents (sEPSCs) in hippocampal neurons from HCAR1 knockout and wild-type mice exposed to lactate.
• Electroencephalography (EEG) to assess seizure burden in HCAR1 knockout and wild-type mice subjected to hypoxia-ischemia (HI).

Main Results:

• HCAR1 expression was detected in the neonatal mouse brain at postnatal day 10, comparable to adult levels.
• Lactate exposure reduced sEPSC amplitude and frequency in wild-type neurons but not in HCAR1 knockout neurons.
• HCAR1 knockout mice exhibited a significantly higher seizure burden and increased behavioral seizure scores following HI compared to wild-type controls.

Conclusions:

• HCAR1 is expressed on neurons in the neonatal brain.
• HCAR1 plays a critical role in regulating neuronal excitability and mitigating seizures in the context of HIE.
• Targeting HCAR1 may offer a therapeutic strategy for neonatal brain injury and seizures.