Micro-imaging Center of Psychiatric Disorder, Institute of Mental Health, Jining Medical University, 272013, Jining, China.
Key Laboratory of Real Time Imaging of Brian Circuits in Psychiatry and Neurology (RTIBNP_Lab), Tianjin Fourth Center Hospital Affiliated to Nankai University, Tianjin Fourth Center Hospital; Tianjin Mental Health Center of Tianjin Medical University, 30022, Tianjin, China.
Transl Psychiatry. 2021 Dec 7;11(1):619. doi: 10.1038/s41398-021-01750-8.
Brain pathological features during manic/hypomanic and depressive episodes in the same patients with bipolar disorder (BPD) have not been described precisely. The study aimed to investigate depressive and manic-phase-specific brain neural activity patterns of BPD in the same murine model to provide information guiding investigation of the mechanism of phase switching and tailored prevention and treatment for patients with BPD. In vivo two-photon imaging was used to observe brain activity alterations in the depressive and manic phases in the same murine model of BPD. Two-photon imaging showed significantly reduced Ca activity in temporal cortex pyramidal neurons in the depression phase in mice exposed to chronic unpredictable mild stress (CUMS), but not in the manic phase in mice exposed to CUMS and ketamine. Total integrated calcium values correlated significantly with immobility times. Brain Ca hypoactivity was observed in the depression and manic phases in the same mice exposed to CUMS and ketamine relative to naïve controls. The novel object recognition preference ratio correlated negatively with the immobility time in the depression phase and the total distance traveled in the manic phase. With recognition of its limitations, this study revealed brain neural activity impairment indicating that intrinsic emotional network disturbance is a mechanism of BPD and that brain neural activity is associated with cognitive impairment in the depressive and manic phases of this disorder. These findings are consistent with those from macro-imaging studies of patients with BPD. The observed correlation of brain neural activity with the severity of depressive, but not manic, symptoms need to be investigated further.
在双相障碍（BPD）患者的同一发作期中，躁狂/轻躁狂和抑郁期的脑部病理特征尚未被准确描述。本研究旨在探讨同一 BPD 啮齿动物模型中抑郁期和躁狂期的特定脑神经活动模式，为研究相转换的机制以及为 BPD 患者提供有针对性的预防和治疗提供信息。采用活体双光子成像技术观察慢性不可预测轻度应激（CUMS）暴露的同一 BPD 啮齿动物模型中抑郁期和躁狂期的大脑活动变化。双光子成像显示，在 CUMS 暴露的抑郁期，颞叶皮质锥体神经元的 Ca 活性显著降低，但在 CUMS 和氯胺酮暴露的躁狂期则没有。总积分钙值与不动时间呈显著正相关。与未处理的对照组相比，CUMS 和氯胺酮暴露的同一组小鼠在抑郁期和躁狂期均观察到脑 Ca 活性降低。新颖物体识别偏好比与抑郁期的不动时间和躁狂期的总行进距离呈负相关。尽管认识到其局限性，但本研究揭示了脑神经活动损伤，表明内在情绪网络紊乱是 BPD 的一种机制，脑神经活动与该疾病抑郁期和躁狂期的认知障碍有关。这些发现与 BPD 患者的宏观成像研究结果一致。需要进一步研究观察到的脑神经活动与抑郁症状严重程度的相关性，而不是躁狂症状严重程度的相关性。
