Heng Vibol, Zigmond Michael, Smeyne Richard Jay
Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA, United States.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States.
Front Neuroanat. 2023 Aug 17;17:1190291. doi: 10.3389/fnana.2023.1190291. eCollection 2023.
As social animals, our health depends in part on interactions with other human beings. Yet millions suffer from chronic social isolation, including those in nursing/assisted living facilities, people experiencing chronic loneliness as well as those in enforced isolation within our criminal justice system. While many historical studies have examined the effects of early isolation on the brain, few have examined its effects when this condition begins in adulthood. Here, we developed a model of adult isolation using mice (C57BL/6J) born and raised in an enriched environment.
From birth until 4 months of age C57BL/6J mice were raised in an enriched environment and then maintained in that environment or moved to social isolation for 1 or 3 months. We then examined neuronal structure and catecholamine and brain derived neurotrophic factor (BDNF) levels from different regions of the brain, comparing animals from social isolation to enriched environment controls.
We found significant changes in neuronal volume, dendritic length, neuronal complexity, and spine density that were dependent on brain region, sex, and duration of the isolation. Isolation also altered dopamine in the striatum and serotonin levels in the forebrain in a sex-dependent manner, and also reduced levels of BDNF in the motor cortex and hippocampus of male but not female mice.
These studies show that isolation that begins in adulthood imparts a significant change on the homeostasis of brain structure and chemistry.
作为社会性动物,我们的健康部分取决于与他人的互动。然而,数百万人遭受着慢性社会隔离之苦,包括那些住在护理/辅助生活设施中的人、经历长期孤独的人以及在刑事司法系统中被强制隔离的人。虽然许多历史研究探讨了早期隔离对大脑的影响,但很少有研究考察这种情况在成年期开始时的影响。在这里,我们利用在丰富环境中出生和长大的小鼠(C57BL/6J)建立了一个成年期隔离模型。
将C57BL/6J小鼠从出生饲养至4个月大,饲养于丰富环境中,之后继续饲养于该环境或转移至社会隔离环境中1个月或3个月。然后,我们检查了来自大脑不同区域的神经元结构、儿茶酚胺和脑源性神经营养因子(BDNF)水平,将处于社会隔离环境中的动物与丰富环境对照组进行比较。
我们发现神经元体积、树突长度、神经元复杂性和棘密度存在显著变化,这些变化取决于脑区、性别和隔离持续时间。隔离还以性别依赖的方式改变了纹状体中的多巴胺和前脑中的血清素水平,并且降低了雄性而非雌性小鼠运动皮层和海马体中的BDNF水平。
这些研究表明,成年期开始的隔离会对大脑结构和化学的稳态产生重大影响。