Programa de Pós-Graduação em Ciências Biológicas: Bioquímica/Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Ramiro Barcelos, 2600 (Anexo) Lab. 37., Porto Alegre, RS, 90035-003, Brazil.
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
Mol Neurobiol. 2018 Apr;55(4):2740-2753. doi: 10.1007/s12035-017-0538-y. Epub 2017 Apr 27.
During development, the brain goes through fundamental processes, including organization of neural networks and plasticity. Environmental interventions may change initial brain programming, leading to long-lasting effects and altering the susceptibility to psychopathologies, including depression disorder. It is known that depression is a psychiatric disorder with a high prevalence worldwide, including high rates among adolescents. In this study, we evaluated whether social isolation in the prepubertal period and chronic use of high-fat diet (HFD) may induce depressive-like behavior in male adult rats. We also investigated hippocampal plasticity markers and neurotransmitter systems. We found both social isolation and HFD induced a depressive-like behavior in the forced swimming task. Moreover, chronic HFD reduced synaptic markers in hippocampus, demonstrated by reductions in βIII-tubulin (neuronal marker), PSD-95, SNAP-25, and neurotrophin-3. The HFD group also presented decreased glutamatergic and GABAergic receptors subunits. On the other hand, stress affected hippocampal brain-derived neurotrophic factor (BDNF) signaling pathways, and increased expression of subunit of the NMDA receptor (NR2A). Both factors (stress and diet) decreased GR in the hippocampus without affecting plasma corticosterone at basal levels. Interactions between early stress and HFD access were observed only in the BNDF receptor (tropomyosin receptor kinase B; TrkB) and synaptophysin. In summary, these findings showed that a brief social isolation and chronic HFD, during a sensitive developmental period, cause depressive-like behavior in adulthood. The mechanisms underlying these behavioral effects may involve changes in the levels of synaptic proteins in hippocampus: HFD consumption appears to affect synaptic markers, while social isolation affected BDNF signaling more significantly.
在发育过程中，大脑经历了包括神经网络组织和可塑性在内的基本过程。环境干预可能会改变初始大脑编程，导致持久的影响，并改变对精神病理学的易感性，包括抑郁症。众所周知，抑郁症是一种精神障碍，在全球范围内患病率很高，包括青少年中的高发病率。在这项研究中，我们评估了青春期前的社交隔离和慢性高脂肪饮食（HFD）是否会导致雄性成年大鼠出现类似抑郁的行为。我们还研究了海马体可塑性标志物和神经递质系统。我们发现社交隔离和 HFD 都会在强迫游泳试验中引起类似抑郁的行为。此外，慢性 HFD 降低了海马体中的突触标志物，表现为 βIII-微管蛋白（神经元标志物）、PSD-95、SNAP-25 和神经营养因子-3 的减少。HFD 组还表现出谷氨酸能和 GABA 能受体亚基的减少。另一方面，应激影响了海马体脑源性神经营养因子（BDNF）信号通路，并增加了 NMDA 受体（NR2A）亚基的表达。这两个因素（应激和饮食）都降低了海马体中的糖皮质激素受体（GR），而对基础水平的血浆皮质酮没有影响。仅在 BDNF 受体（原肌球蛋白受体激酶 B；TrkB）和突触小体蛋白中观察到早期应激和 HFD 摄入之间的相互作用。总之，这些发现表明，在敏感的发育时期，短暂的社交隔离和慢性 HFD 会导致成年期出现类似抑郁的行为。这些行为效应的机制可能涉及海马体中突触蛋白水平的变化：HFD 摄入似乎会影响突触标志物，而社交隔离则更显著地影响 BDNF 信号。
