Lotter Jana, Möller Marisa, Dean Olivia, Berk Michael, Harvey Brian H
Division of Pharmacology, Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North West University, Potchefstroom, South Africa.
Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
Front Psychiatry. 2020 Mar 31;11:121. doi: 10.3389/fpsyt.2020.00121. eCollection 2020.
Schizophrenia is a severe brain disorder that is associated with neurodevelopmental insults, such as prenatal inflammation, that introduce redox-immune-inflammatory alterations and risk for psychotic symptoms later in life. Nutraceuticals may offer useful adjunctive benefits. The aim of this study was to examine the therapeutic effects of Linn (GML) and one of its active constituents, α-mangostin (AM), alone and as adjunctive treatment with haloperidol (HAL) on schizophrenia related bio-behavioral alterations in a maternal immune-activation (MIA) model. Sprague-Dawley dams were exposed to lipopolysaccharide (LPS) ( = 18) or vehicle ( = 3) on gestational days 15 and 16. Male offspring ( = 72) were treated from PND 52-66 with either vehicle, HAL (2 mg/kg), GML (50 mg/kg), HAL + GML, AM (20 mg/kg), or HAL + AM. Control dams and control offspring were treated with vehicle. In order to cover the mood-psychosis continuum, prepulse inhibition (PPI) of startle, open field test (locomotor activity), and the forced swim test (depressive-like behavior) were assessed on PND's 64-65, followed by assay of frontal-cortical lipid peroxidation and plasma pro-inflammatory cytokines, . interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α). MIA-induced deficits in sensorimotor gating were reversed by HAL and HAL + GML, but not GML and AM alone. MIA-induced depressive-like behavior was reversed by AM and GML alone and both in combination with HAL, with the combinations more effective than HAL. MIA-induced cortical lipid peroxidation was reversed by HAL and AM, with elevated IL-6 levels restored by GML, AM, HAL, and HAL + GML. Elevated TNF-α was only reversed by GML and HAL + GML. Concluding, prenatal LPS-induced psychotic- and depressive-like bio-behavioral alterations in offspring are variably responsive to HAL, GML, and AM, with depressive (but not psychosis-like) manifestations responding to GML, AM, and combinations with HAL. AM may be a more effective antioxidant than GML , although this does not imply an improved therapeutic response, for which trials are required.
精神分裂症是一种严重的脑部疾病，与神经发育损伤有关，如产前炎症，这种炎症会引发氧化还原 - 免疫 - 炎症改变，并增加日后出现精神病症状的风险。营养保健品可能具有有益的辅助作用。本研究的目的是在母体免疫激活（MIA）模型中，研究藤黄果（GML）及其活性成分之一α - 山竹黄酮（AM）单独使用以及与氟哌啶醇（HAL）联合使用对精神分裂症相关生物行为改变的治疗效果。在妊娠第15天和第16天，将斯普拉格 - 道利孕鼠暴露于脂多糖（LPS）（n = 18）或赋形剂（n = 3）中。雄性后代（n = 72）在出生后第52 - 66天接受以下处理：赋形剂、HAL（2 mg/kg）、GML（50 mg/kg）、HAL + GML、AM（20 mg/kg）或HAL + AM。对照孕鼠和对照后代接受赋形剂处理。为了涵盖情绪 - 精神病连续体，在出生后第64 - 65天评估惊吓前脉冲抑制（PPI）、旷场试验（运动活动）和强迫游泳试验（抑郁样行为），随后检测额叶皮质脂质过氧化和血浆促炎细胞因子，即白细胞介素 - 1（IL - 1）和肿瘤坏死因子 - α（TNF - α）。HAL和HAL + GML可逆转MIA诱导的感觉运动门控缺陷，但单独使用GML和AM则不能。单独使用AM和GML以及两者与HAL联合使用均可逆转MIA诱导的抑郁样行为，联合使用比HAL更有效。HAL和AM可逆转MIA诱导的皮质脂质过氧化，GML、AM、HAL和HAL + GML可使升高的IL - 6水平恢复正常。升高的TNF - α仅被GML和HAL + GML逆转。总之，产前LPS诱导的后代精神病性和抑郁样生物行为改变对HAL、GML和AM的反应各不相同，抑郁（而非类精神病）表现对GML、AM以及与HAL联合使用有反应。AM可能是比GML更有效的抗氧化剂，尽管这并不意味着治疗反应会改善，仍需要进行试验。
