常常玩土未必是件坏事。根据发表在近期《神经科学》(Neuroscience)杂志上的一项研究,一种土壤中的常见细菌能够激活大脑中的神经元,从而制造出一种负责调控情绪的化学物质——血清素(serotonin,也称色胺)。
通常认为,缺乏血清素会使人精神抑郁消沉,而最新研究结果将加深人们对免疫系统失衡导致一些人情绪低落的科学认识。进行该研究的是英国布里斯托尔大学(University of Bristol)和伦敦大学学院(University College London,简称UCL)的科学家,他们对该研究的兴趣源于偶然。科学家意外发现,利用母牛分枝杆菌(Mycobacterium vaccae)对一些癌症病人进行治疗后,他们的生活质量有所增加。论文第一作者、布里斯托尔大学Chris Lowry博士和同事认为,造成这一结果的原因可能是产生血清素的大脑神经元被激活。
利用小鼠进行的研究证实了这一猜测。Lowry和同事发现,母牛分枝杆菌能够激活小鼠大脑中一组制造血清素的神经元,从而改善小鼠的情绪和行为活动。
Lowry表示,该研究有助于人们理解身体和大脑的沟通机制,以及良好的免疫系统对维持精神健康的重要性。
部分英文原文:
Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior
C.A. Lowrya, , , J.H. Hollisa, 1, A. de Vriesa, 1, B. Pana, L.R. Brunetb, J.R.F. Huntb, J.F.R. Patonc, E. van Kampena, D.M. Knighta, A.K. Evansa, G.A.W. Rookb and S.L. Lightmana
aHenry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Bristol BS1 3NY, UK
bCentre for Infectious Diseases and International Health, Windeyer Institute of Medical Sciences, University College London, W1T 4JF, UK
cDepartment of Physiology, Bristol Heart Institute, University of Bristol, School of Medical Sciences, Bristol, BS8 1TD, UK
Accepted 30 January 2007. Available online 28 March 2007.
Abstract
Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes.
Key words: depression; hippocampus; prefrontal cortex; raphe; 5-HT; vagus
Abbreviations: ANOVA, analysis of variance; AP, area postrema; c-Fos-ir, c-Fos-like-immunoreactive; DR, dorsal raphe nucleus;DRC, dorsal raphe nucleus, caudal part; DRI, dorsal raphe nucleus, interfascicular part; ECG, electrocardiogram; EDTA, ethylenediaminetetraacetic acid; EMG, electromyogram; HPLC, high pressure liquid chromatography; IL-6, interleukin-6; IL-10, interleukin-10; i.t., intratracheal; LPS, lipopolysaccharide; LSD, least significant difference; mlf, medial longitudinal fasciculus; M. vaccae, Mycobacterium vaccae; Mv-NC, Mycobacterium vaccae antigen, M. vaccae coupled to nitrocellulose beads; NC, nitrocellulose beads; nTS, nucleus of the solitary tract; OVA, ovalbumin; OVA-NC, ovalbumin coupled to nitrocellulose beads; PBG, phenylbiguanide; PBS, phosphate-buffered saline; PBST, phosphate-buffered saline containing 0.3% Triton X-100; RMg, raphe magnus; ROb, raphe obscurus; S.E.M., standard error of the mean; SolDL, dorsolateral part of the nucleus of the solitary tract; TGF-β, transforming growth factor-β; Th1, T helper cell 1; Th2, T helper cell 2; TNF-α, tumor necrosis factor-α; Treg, T regulatory cell; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, serotonin
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1 These authors contributed equally to this work.