Alpha-linolenic acid enhances the facilitation of GABAergic neurotransmission in the BLA and CA1

Experimental Biology and Medicine, 2023 · DOI: 10.1177/15353702231165010 · Published: April 1, 2023

Simple Explanation

Hyperexcitability in the brain is implicated in several neuropsychiatric disorders. A common finding in these disorders is the dysfunction and loss of GABA inhibitory neurons. Alpha-linolenic acid (ALA) is an essential omega-3 polyunsaturated fatty acid found in plants, and it has shown promise in attenuating injury in brain disease models. This study shows that ALA increases GABAA receptor inhibitory activity in the BLA and CA1 pyramidal neurons. A BDNF-TrkB-mediated mechanism is suggested.

Study Duration

Not specified

Participants

26 male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Administration of ALA increased the charge transfer of inhibitory postsynaptic potential currents mediated by GABAA receptors in pyramidal neurons in the BLA and CA1 compared to vehicle animals.
2
Pretreatment with a TrkB inhibitor abolished the ALA-induced increase in GABAergic neurotransmission in the BLA and CA1, suggesting a BDNF-mediated mechanism.
3
Addition of mature BDNF increased GABAA receptor inhibitory activity in the BLA and CA1 pyramidal neurons similar to the results obtained with ALA.

Research Summary

This study demonstrates that ALA increases GABAAR-mediated inhibitory activity in the BLA and CA1 pyramidal neurons 24 h after injection in young adult Sprague-Dawley male rats. The study showed that ALA facilitates GABAergic neurotransmission in the BLA and CA1 subfield of the hippocampus via a TrkB-dependent mechanism to increase GABAA receptor inhibitory activity. The ALA-induced increase in GABAAR inhibitory activity is replicated by the bath application of mature BDNF. The addition of the high-affinity TrkB inhibitor, k252a, abolishes the ALA-induced increase.

Practical Implications

Therapeutic Potential

ALA may be a viable treatment strategy for neuropsychiatric disorders where hyperexcitability is a major feature.

Neuroprotective Mechanism

ALA may elicit neuroprotective effects by reducing the excitotoxic effect of glutamate and enhancing the inhibitory GABAergic system.

GABAergic system modulation

ALA may have opposing effects on the glutamatergic and GABAergic systems under excitotoxic conditions.

Study Limitations

1
The exact mechanism by which ALA mediates the release of mature BDNF is unknown.
2
The effect of ALA of much lower intensity could be observed only after more than 15- to 20-min washout of ALA.
3
Conflicting results may be explained by the fact that our studies were performed in brain slices where network circuitry remains intact, whereas the above studies were performed in enriched isolated neuronal cultures in vitro.

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