Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-170, RJ, Brazil.
Departamento de Ciências, Faculdade de Formação de Professores da Universidade do Estado do Rio de Janeiro, São Gonçalo 24435-005, RJ, Brazil.
Int J Mol Sci. 2023 Sep 27;24(19):14634. doi: 10.3390/ijms241914634.
Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence.
青少年时期经常发现精神分裂症的烟草使用不当是一种共病。然而，目前仍然缺乏共病标志物。在这里，使用无标签蛋白质组学方法来鉴定有吸烟史的雄性和雌性小鼠的内侧前额叶皮层（额前皮质和下额皮质）中失调蛋白。使用苯环己哌啶（PCP）来模拟精神分裂症（SCHZ），并结合已建立的尼古丁微量泵输注（NIC）模型。当考虑到失调蛋白的绝对数量和专门失调的蛋白数量时，联合刺激导致的结果比每种刺激单独使用时更差。性别之间和 PCP、NIC 和 PCPNIC 组之间部分共享的 Reactome 途径表明存在功能重叠。独特的是，仅在 PCPNIC 小鼠中差异表达的蛋白质揭示了与共病模型相关的独特作用。这些蛋白质的互作图谱确定了性选择子网，其中一些蛋白质脱颖而出：对于女性，肽脯氨酰顺反异构酶（Fkbp1a）和热休克 70 kDa 蛋白 1B（Hspa1b），都是氧化应激子网的组成部分，以及γ-烯醇酶（Eno2），是能量代谢子网的组成部分；对于男性， amphiphysin（Amph），是突触传递子网的组成部分。这些被提议进一步进行调查和验证，作为青少年时期联合刺激的标志物。
