Glutamine triggers long-lasting increase in striatal network activity in vitro

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Hepatic encephalopathy (HE) involves brain ammonia and glutamine accumulation.
• Ammonia's neurotoxicity is known, but glutamine is considered detoxified.
• HE patients show brain abnormalities, particularly in the basal ganglia and striatum.

Purpose of the Study:

• To investigate the role of glutamine, beyond ammonia, in neuronal excitation.
• To explore the mechanisms of glutamine's effect on striatal and cortical cells.
• To determine if glutamine contributes to the neuropsychiatric symptoms of HE.

Main Methods:

• Culturing rat striatal and cortical cells on microelectrode arrays.
• Applying ammonium and glutamine to assess effects on spontaneous spike rates.
• Utilizing calcium imaging to observe intracellular calcium changes.
• Employing enzymatic assays, real-time PCR, and immunocytochemistry to detect glutamate release and transporters.

Main Results:

• Glutamine significantly increased neuronal firing rates, causing long-lasting excitation, more so in striatal cells.
• Glutamine-induced excitation involved system A amino acid transport and glutamate receptors.
• Evidence confirmed glutamine triggers glutamate release from striatal neurons via vesicular glutamate transporters.

Conclusions:

• Extracellular glutamine uptake by neurons leads to synaptic glutamate release.
• A feedback loop involving astrocytes converting glutamate back to glutamine sustains neuronal excitation.
• Glutamine, like ammonia, may contribute to the neuropsychiatric symptoms observed in hepatic encephalopathy.