Research press release


Nature Medicine

Rewarding activation gives mice an immune boost

脳の報酬中枢は、本来的に報酬につながる刺激や肯定的予測にかかわる神経回路で構成されている。こうした中枢を活性化すると、特定の病原体〔今回は大腸菌(Escherichia coli)〕に対する体の免疫防御に影響が及ぶことが報告された。  前向きな感情や期待は脳の報酬回路を活性化し、これは免疫系の働きなどの複数の生理的過程に影響する。しかし、脳の特定の領域や細胞が末梢免疫及ぼす影響は、正確には分かっていなかった。


A Rolls、S Shen-Orrたちは、マウスで遺伝学的手法を用い、脳の腹側被蓋野(VTA)のドーパミン作動性ニューロン内だけでDREADD(Designer Receptors Exclusively Activated by Designer Drug)と呼ばれる改変受容体を発現させた。VTAからのドーパミン性入力は報酬中枢の活動を高める。そこで、マウスを大腸菌に曝露する1日前にこの受容体を活性化しておくと、短期実験でも長期実験でも、末梢の免疫細胞の大腸菌に対する防御能が上昇することが分かった。このような影響は末梢交感神経系を不活性化すると抑制されるので、この系が脳の報酬中枢の回路と末梢免疫系とを結びつけているらしい。



Activation of one of the brain’s reward centers - composed of neural circuits that are normally engaged by naturally rewarding stimuli and positive expectations - influences the body’s immune defense against a specific bacterial pathogen (Escherichia coli), reports a study in mice published online this week in Nature Medicine.

Positive emotions and expectations activate the reward circuitry in the brain, which affects multiple physiological processes, including the functioning of the immune system. However, the precise influence of specific brain regions and cell types on peripheral immunity has remained unknown.

Asya Rolls, Shai Shen-Orr and colleagues employed genetic methods to achieve the expression of engineered receptors called DREADDs, or designer receptors exclusively activated by designer drugs, exclusively within dopaminergic neurons of the ventral tegmental area (VTA) of the mouse brain. To enhance activity in this reward center, the authors activated these receptors one day before an immune challenge with Escherichia coli bacteria, and observed an increase in the ability of peripheral immune cells to defend against the bacteria in both short- and long-term experiments. These effects are suppressed by the inactivation of the peripheral sympathetic nervous system, which suggests that this system acts as a bridge between the central brain reward circuits and the peripheral immune system.

Although the idea has not yet been experimentally tested, this study may provide a biological basis for the well-known placebo effect, in which a patient’s positive expectations can lead to physiological improvements in a variety of health conditions. Further work will be required to investigate the circumstances under which this brain-immune system might operate, although the authors speculate that naturally rewarding stimuli, such as mating or feeding behaviors, might both activate the VTA and increase the likelihood of potential exposure to pathogens. In addition, understanding whether this brain-immune system connection influences immune defense against other pathogens, such as viruses, will require further investigation.

doi: 10.1038/nm.4133


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