Intake of 7,8-Dihydroxyflavone During Juvenile and Adolescent Stages Prevents Onset of Psychosis in Adult Offspring After Maternal Immune Activation.
Intake of 7,8-Dihydroxyflavone During Juvenile and Adolescent Stages Prevents Onset of Psychosis in Adult Offspring After Maternal Immune Activation.
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DOI：
10.1038/srep36087
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发表时间：
2016-11-08
影响因子：
4.6
通讯作者：
Hashimoto K
中科院分区：
文献类型：
--
作者：
Han M;Zhang JC;Yao W;Yang C;Ishima T;Ren Q;Ma M;Dong C;Huang XF;Hashimoto K
产前感染和随后的后代神经发育异常与精神分裂症的病因有关。脑源性神经营养因子（BDNF）及其高亲和受体原肌球蛋白受体激酶B （TrkB）信号在神经发育中起关键作用。孕鼠暴露于多核糖素-多核糖素酸[poly(I:C)]会导致其后代在成年后出现类似精神分裂症的行为异常。在这里，我们发现poly（I:C）处理小鼠的幼崽表现出认知缺陷，以及前额皮质（PFC）中BDNF-TrkB信号的减少。此外，poly（I:C）处理小鼠的成年后代出现认知缺陷，脉冲前抑制（PPI）缺陷，BDNF-TrkB信号传导降低，内侧PFC和海马CA1前边缘（PrL）的小白蛋白（PV）和过氧化物酶体增殖物激活受体γ共激活因子1α (PGC-1α)的免疫反应性降低。在幼年期和青春期补充TrkB激动剂7,8-二羟黄酮（饮用水中1 mg/mL）可以预防这些行为异常，降低PFC和CA1中的BDNF-TrkB信号，以及poly（I:C）处理小鼠成年后代内侧PFC和CA1 PrL中PV和PGC-1α的免疫反应性。这些发现表明，对精神病超高风险受试者进行TrkB激动剂的早期干预可能会降低随后过渡到精神分裂症的风险。
Prenatal infection and subsequent abnormal neurodevelopment of offspring is involved in the etiology of schizophrenia. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB) signaling plays a key role in the neurodevelopment. Pregnant mice exposed to polyriboinosinic-polyribocytidylic acid [poly(I:C)] causes schizophrenia-like behavioral abnormalities in their offspring at adulthood. Here we found that the juvenile offspring of poly(I:C)-treated mice showed cognitive deficits, as well as reduced BDNF-TrkB signaling in the prefrontal cortex (PFC). Furthermore, the adult offspring of poly(I:C)-treated mice showed cognitive deficits, prepulse inhibition (PPI) deficits, reduced BDNF-TrkB signaling, immunoreactivity of parvalbumin (PV) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the prelimbic (PrL) of medial PFC and CA1 of hippocampus. Supplementation of a TrkB agonist 7,8-dihydroxyflavone (1 mg/mL in drinking water) during juvenile and adolescent stages could prevent these behavioral abnormalities, reduced BDNF-TrkB signaling in PFC and CA1, and immunoreactivity of PV and PGC-1α in the PrL of medial PFC and CA1 in the adult offspring from poly(I:C)-treated mice. These findings suggest that early intervention by a TrkB agonist in subjects with ultra-high risk for psychosis may reduce the risk of subsequent transition to schizophrenia.
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