Das Saroj Kumar, Barhwal Kalpana, Hota Sunil Kumar, Thakur Mahendra Kumar, Srivastava Ravi Bihari
Experimental Biology Division, Defence Institute of High Altitude Research, Defence Research Development Organisation, Leh-Ladakh, C/O- 56 APO, Jammu and Kashmir, 901205, India.
Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
BMC Neurosci. 2015 Feb 14;16:2. doi: 10.1186/s12868-015-0141-y.
Although there have been several reports on social isolation induced mood alterations, the independent contribution of monotonous environment in mediating mood alterations has been less studied. In view of the above, the present study is aimed at investigating the relative contribution of monotony towards mood alterations during isolation stress. Monotony was induced in a specially designed isolation chamber in male Sprague-Dawley rats in the presence or absence of isolation by housing animals singly (SH) or in pairs (PH). Novel objects were introduced to disrupt monotony in singly housed animals (SHNO) or paired housed animals (PHNO). Behavioural alterations were assessed using Open field test (OFT), Elevated Plus Maze (EPM) and Forced Swim Test (FST). Neuro-morphological changes in the CA3 region of hippocampus were studied by cresyl violet and golgi-cox staining. Hippocampal serotonin and 5-hydroxy indole acetic acid (5-HIAA) levels were estimated along with the expression of phospho-insulin like growth factor-1 receptor (pIGF-1R) and phospho cyclic AMP response-element binding protein (pCREB). Serotonin was depleted by administering Para-chlorophenylalanine (PCPA) to a separate PH group (PHPCPA), PHNO group (PHNOPCPA) and SHNO group (SHNOPCPA) to determine the role of serotonin in mediating monotony induced emotional mal-adaptations.
The results showed anxiety and depression like traits in both PH and SH groups during behavioural test such as OFT, EPM and FST. Pyknosis along with decrease in apical dendritic arborization was observed in the CA3 region of SH group along with decrease in serotonin and reduced expression of pIGF-1R and pCREB. Disrupting monotony through intervention of novel objects in PHNO and SHNO groups ameliorated anxiety and depression like traits and augmented pIGF-1R along with increase in serotonin level. Depletion of hippocampal serotonin level by PCPA administration in PHNOPCPA and SHNOPCPA groups on the other hand resulted in altered mood state despite disruption of monotony by novel objects intervention.
The findings of our study suggest that monotonous environment independently contributes to impairment in mood state and disrupting monotony by intervention of novel objects during social isolation prevents mood disorders and emotional maladaptation through up regulation of hippocampal pIGF-1R and increase in serotonin.
尽管已有多篇关于社会隔离诱发情绪改变的报道,但单调环境在介导情绪改变中的独立作用却鲜有研究。鉴于此,本研究旨在探究单调在隔离应激期间对情绪改变的相对作用。通过将雄性Sprague-Dawley大鼠单独饲养(SH)或成对饲养(PH),在有或无隔离的情况下,于专门设计的隔离箱中诱发单调状态。向单独饲养的动物(SHNO)或成对饲养的动物(PHNO)引入新物体以打破单调状态。使用旷场试验(OFT)、高架十字迷宫(EPM)和强迫游泳试验(FST)评估行为改变。通过甲酚紫和高尔基-考克斯染色研究海马CA3区的神经形态变化。测定海马5-羟色胺和5-羟吲哚乙酸(5-HIAA)水平以及磷酸化胰岛素样生长因子-1受体(pIGF-1R)和磷酸化环磷腺苷反应元件结合蛋白(pCREB)的表达。通过向单独的PH组(PHPCPA)、PHNO组(PHNOPCPA)和SHNO组(SHNOPCPA)给予对氯苯丙氨酸(PCPA)耗尽5-羟色胺,以确定5-羟色胺在介导单调诱发的情绪适应不良中的作用。
行为测试(如OFT、EPM和FST)结果显示,PH组和SH组均出现焦虑和抑郁样特征。SH组的CA3区观察到细胞核固缩以及顶端树突分支减少,同时5-羟色胺水平降低,pIGF-1R和pCREB表达减少。通过在PHNO组和SHNO组中引入新物体打破单调状态,改善了焦虑和抑郁样特征,并增加了pIGF-1R以及5-羟色胺水平。另一方面,在PHNOPCPA组和SHNOPCPA组中给予PCPA耗尽海马5-羟色胺水平,尽管通过引入新物体打破了单调状态,但仍导致情绪状态改变。
我们的研究结果表明,单调环境独立导致情绪状态受损,在社会隔离期间通过引入新物体打破单调状态可通过上调海马pIGF-1R和增加5-羟色胺预防情绪障碍和情绪适应不良。