2023-11-16 14:15:00
▲ When the expression of PLCγ1 was specifically suppressed genetically in dopaminergic neurons, dopamine secretion was confirmed to increase in the axon terminals of dopaminergic neurons/(A) Increase in VMAT2 and synapsin III in the axon terminals of dopaminergic neurons in PLCγ1-deficient mice. A summary of the research results showing that dopamine secretion increased compared to normal mice. (B) Dopamine release was induced by electrically stimulating the dorsal striatum (Dstr) and the nucleus accumbens core (NAc core), where the axon terminals of dopamine neurons are located, and a fast-scan cyclic voltmeter (FSCV) experiment. The change in dopamine concentration over time was measured. (C) Graph of changes in voltage-current according to dopamine release from the axon terminal of dopamine neurons in the dorsal striatum when electrical stimulation is applied. (D) Dopamine release was confirmed to be increased in the dorsal striatum of PLCγ1-deficient mice. (E) Graph of voltage-current changes according to dopamine release from the axon terminals of dopamine neurons in the center of the nucleus accumbens when electrical stimulation is applied. (F) Increased dopamine release was observed in the center of the nucleus accumbens of PLCγ1-deficient mice, confirming that genetic inhibition of PLCγ1 expression at the axon terminals of dopaminergic neurons has a significant effect on dopamine secretion. (Figure and explanation) =UNIST) © Patent News
A new way to regulate dopamine secretion has been discovered. It is expected that it will contribute to the development of treatments for dopamine-related brain diseases.
Professor Jaeik Kim’s team in the Department of Life Sciences at UNIST announced new research results showing that PLCγ1 protein, a key signal transduction element in dopaminergic neurons, regulates dopamine secretion.
Dopamine is a neurotransmitter present in the central nervous system that performs various functions related to voluntary movement, motivation, and emotional regulation. Adequate secretion of dopamine causes positive effects such as happiness and reward. However, if there is a problem with secretion, various brain function abnormalities such as depression, anxiety, hyperactivity, and reduced motor skills may occur.
Dopamine is mainly synthesized in dopaminergic neurons in the midbrain. The synthesized dopamine is secreted into the striatum and nucleus accumbens, where the nerve fiber terminals of neurons are distributed. The striatum plays an important role in voluntary movement, and the nucleus accumbens is a part of the brain that processes information about motivation and reward.
The synthesized dopamine moves to ‘synaptic vesicles’ that store neurotransmitters for secretion. This accumulated dopamine searches for a synapse where it can be released. In this process, vesicular monoamine transporter (VMAT2), which transports dopamine to synaptic vesicles, and synapsin III, which moves vesicles to synapses where they can be released, are known to play important roles.
The research team found that dopamine secretion increased in the striatum and nucleus accumbens, brain regions of a mouse model in which the PLCγ1 gene was incompletely created in dopamine neurons. It was revealed that the amounts of VMAT2 and Synapsin III increased at the terminals of dopamine nerve fibers, and that these changes play a critical role in increasing dopamine secretion. In other words, this study was the first to reveal that PLCγ1 protein directly regulates dopamine secretion.
Professor Kim Jae-ik of the Department of Biological Sciences said, “Previously, it was difficult to identify the signaling mechanism within dopamine neurons due to limitations in experimental methods,” and “With improvements in real-time dopamine measurement in vivo and high-resolution synapse imaging methods, the role of PLCγ1 specific to dopamine neurons has been discovered.” “We were able to newly identify it,” he explained.
Researcher Kim Hye-yoon, the first author, expected that “by identifying the PLCγ1-mediated signaling method involved in regulating dopamine secretion, we will be able to contribute to the development of treatments for dopamine-related brain diseases.”
This study was conducted in collaboration with the Korea Brain Research Institute and was published on November 1 in ‘Experimental & Molecular Medicine (EMM)’, a major academic journal in the life sciences field.
논문명은 PLCγ1 in dopamine neurons critically regulates striatal dopamine release via VMAT2 and synapsin Ⅲ 이다.
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