Ayilara Gideon Opeyemi, Owoyele Bamidele Victor
Neuroscience and Inflammation Unit, Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Kwara, Nigeria.
IBRO Neurosci Rep. 2023 Jun 3;15:31-41. doi: 10.1016/j.ibneur.2023.05.010. eCollection 2023 Dec.
Schizophrenia is a psychiatric disorder with a global prevalence of approximately 0.45%. It is considered a mental illness, with negative symptoms, positive symptoms, and cognitive dysfunction. The outcomes of studies on the role of microglia and neuroinflammation have been conflicting. In addition, there is a poor understanding of the sex differences in microglial expression and neuroinflammation markers in the prefrontal cortex, hippocampus, and nucleus accumbens. Understanding the exact roles of neuroinflammation may guide the development of efficient therapeutic drugs that can address the negative, positive, and cognitive symptoms of the disease. We examined the effect of social isolation rearing on schizophrenia-related behaviours in male and female BALB/c mice. The social-isolation rearing protocol started on post-natal day (PND) 21, lasting for 35 days. Animals were assigned to four cohorts, consisting of five animals per group. On PND 56, animals were assessed for behavioural changes. We used enzyme-linked immunosorbent assays to investigate the expression of nuclear factor kappa B (NF-κB), tumour necrosis factor-α (TNF-α), and Interleukin-1β (IL-1β) in the hippocampus, nucleus accumbens, and prefrontal cortex. Immunohistochemistry was used to assess the expression of microglia in the three brain regions. Our study showed that isolation rearing led to increasing locomotion, heightened anxiety, depression, and a reduced percentage of prepulse inhibition. There was a significant increase (p < 0.05) in anxiety in the female isolation mice compared to male isolation mice. Furthermore, isolation rearing significantly increased microglia count (p < 0.05) in the hippocampus, nucleus accumbens, and prefrontal cortex, only in the male group. There was microglial hyper-activation as evident in the downregulation of CX3CR1 in both male and female social-isolation groups. Male social-isolation mice showed a significant increase (p < 0.05) in neuroinflammation markers only in the nucleus accumbens while the female social-isolation mice showed a significant increase (p < 0.05) in neuroinflammation markers in both the nucleus accumbens and hippocampus. The study showed that therapeutic interventions aimed at modulating CX3CR1 activity and reducing inflammation may be beneficial for patients with schizophrenia.
精神分裂症是一种全球患病率约为0.45%的精神疾病。它被认为是一种伴有阴性症状、阳性症状和认知功能障碍的精神疾病。关于小胶质细胞和神经炎症作用的研究结果一直存在矛盾。此外，人们对前额叶皮质、海马体和伏隔核中小胶质细胞表达和神经炎症标志物的性别差异了解甚少。了解神经炎症的确切作用可能会指导开发有效的治疗药物，以解决该疾病的阴性、阳性和认知症状。我们研究了社会隔离饲养对雄性和雌性BALB/c小鼠精神分裂症相关行为的影响。社会隔离饲养方案从出生后第21天（PND 21）开始，持续35天。将动物分为四个队列，每组五只动物。在PND 56时，对动物的行为变化进行评估。我们使用酶联免疫吸附测定法研究海马体、伏隔核和前额叶皮质中核因子κB（NF-κB）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达。免疫组织化学用于评估三个脑区中小胶质细胞的表达。我们的研究表明，隔离饲养导致运动增加、焦虑加剧、抑郁以及前脉冲抑制百分比降低。与雄性隔离小鼠相比，雌性隔离小鼠的焦虑显著增加（p < 0.05）。此外，仅在雄性组中，隔离饲养显著增加了海马体、伏隔核和前额叶皮质中的小胶质细胞数量（p < 0.05）。在雄性和雌性社会隔离组中，CX3CR1的下调表明存在小胶质细胞过度激活。雄性社会隔离小鼠仅在伏隔核中神经炎症标志物显著增加（p < 0.05），而雌性社会隔离小鼠在伏隔核和海马体中神经炎症标志物均显著增加（p < 0.05）。该研究表明，旨在调节CX3CR1活性和减轻炎症的治疗干预可能对精神分裂症患者有益。
