近日,，一項(xiàng)發(fā)表于《生物精神病學(xué)》（Biological Psychiatry）雜志的研究中,，來自耶魯大學(xué)醫(yī)學(xué)院的Elsayed和他的團(tuán)隊(duì)發(fā)現(xiàn)：成纖維細(xì)胞生長(zhǎng)因子-2（FGF2）可以促進(jìn)神經(jīng)膠質(zhì)細(xì)胞的增殖，并抑制其減少,，從而增加膠質(zhì)細(xì)胞的數(shù)量,。
該研究的作者Ronald Duman 說“這項(xiàng)研究發(fā)現(xiàn)了一種靶向治療抑郁癥的新途徑，我們可以通過促進(jìn)膠質(zhì)細(xì)胞的生成與維持,，為神經(jīng)元執(zhí)行其功能提供良好的環(huán)境支持,。”
大腦影像學(xué)和尸檢研究發(fā)現(xiàn)抑郁癥患者的大腦內(nèi)連接通路大量減少，情感調(diào)節(jié)相關(guān)腦區(qū)的連接功能受損,。神經(jīng)膠質(zhì)細(xì)胞對(duì)神經(jīng)元的生長(zhǎng)與功能維持起重要支持作用,，尸檢病理報(bào)告顯示抑郁癥患者腦組織中神經(jīng)膠質(zhì)細(xì)胞明顯減少。
既往研究已經(jīng)證實(shí)抗抑郁藥對(duì)大腦結(jié)構(gòu)產(chǎn)生積極影響,，從而改善抑郁癥狀,，而這種積極影響在絕大程度上取決于它們促進(jìn)大腦中生長(zhǎng)因子水平升高的能力。
為探討FGF2是否可以治療抑郁癥,，研究者采用各種可以引起抑郁癥狀（絕望及快感缺失）的自然壓力制作嚙齒類動(dòng)物抑郁模型,，發(fā)現(xiàn)腦室內(nèi)灌入FGF2可以恢復(fù)慢性壓力所致的神經(jīng)膠質(zhì)細(xì)胞減少。數(shù)據(jù)顯示抗抑郁藥物通過增強(qiáng)FGF2的信號(hào)來促進(jìn)膠質(zhì)細(xì)胞增殖與功能,。
“越深入抗抑郁藥作用的生物學(xué)機(jī)制,，越復(fù)雜，然而這種復(fù)雜使科學(xué)的力量更強(qiáng)大,，我們可以發(fā)現(xiàn)抗抑郁藥治療的局限,，從而去尋求更新,、更有效的治療途徑”,，《生物精神病學(xué)》的編輯，耶魯大學(xué)醫(yī)學(xué)院精神病學(xué)系的首席John Krystal評(píng)論,。（生物谷Bioon.com）
doi:10.1016/j.biopsych.2012.03.003
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PMID:
Antidepressant Effects of Fibroblast Growth Factor-2 in Behavioral and Cellular Models of Depression
Maha Elsayed, Mounira Banasr, Vanja Duric, Neil M. Fournier, Pawel Licznerski, Ronald S. Duman
Background
Basic and clinical studies report that the expression of fibroblast growth factor-2 (FGF-2) is decreased in the prefrontal cortex (PFC) of depressed subjects or rodents exposed to stress and increased following antidepressant treatment. Here, we aim to determine if 1) FGF-2/fibroblast growth factor receptor (FGFR) signaling is sufficient and required for mediating an antidepressant response behaviorally and cellularly; and 2) if the antidepressant actions of FGF-2 are mediated specifically by the PFC.
Methods
The role of FGF-2 signaling in behavioral models of depression and anxiety was tested using chronic unpredictable stress (CUS)/sucrose consumption test (SCT), forced swim test (FST), and novelty suppressed feeding test (NSFT). We also assessed the number of bromodeoxyuridine labeled dividing glial cells in the PFC as a cellular index relevant to depression (i.e., decreased by stress and increased by antidepressant treatment).
Results
Chronic FGF-2 infusions (intracerebroventricular) blocked the deficit in SCT caused by CUS. Moreover, the response to antidepressant treatment in the CUS/SCT and FST was abolished upon administration of an inhibitor of FGFR activity, SU5402. These results are consistent with the regulation of proliferating cells in the PFC, a portion of which are of oligodendrocyte lineage. Lastly, subchronic infusions of FGF-2 into the PFC but not into the dorsal striatum produced antidepressant-like and anxiolytic-like effects on FST and NSFT respectively.
Conclusions
These findings demonstrate that FGF-2/FGFR signaling is sufficient and necessary for the behavioral, as well as gliogenic, actions of antidepressants and highlight the PFC as a brain region sensitive to the antidepressant actions of FGF-2.
