近日，一項發(fā)表于《生物精神病學》（Biological Psychiatry）雜志的研究中,，來自耶魯大學醫(yī)學院的Elsayed和他的團隊發(fā)現(xiàn)：成纖維細胞生長因子-2（FGF2）可以促進神經(jīng)膠質(zhì)細胞的增殖,，并抑制其減少，從而增加膠質(zhì)細胞的數(shù)量,。
該研究的作者Ronald Duman 說“這項研究發(fā)現(xiàn)了一種靶向治療抑郁癥的新途徑,，我們可以通過促進膠質(zhì)細胞的生成與維持，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)細胞對神經(jīng)元的生長與功能維持起重要支持作用,，尸檢病理報告顯示抑郁癥患者腦組織中神經(jīng)膠質(zhì)細胞明顯減少,。
既往研究已經(jīng)證實抗抑郁藥對大腦結(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大腦中生長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物抑郁模型,，發(fā)現(xiàn)腦室內(nèi)灌入FGF2可以恢復慢性壓力所致的神經(jīng)膠質(zhì)細胞減少,。數(shù)據(jù)顯示抗抑郁藥物通過增強FGF2的信號來促進膠質(zhì)細胞增殖與功能。
“越深入抗抑郁藥作用的生物學機制,，越復雜,，然而這種復雜使科學的力量更強大，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》的編輯,，耶魯大學醫(yī)學院精神病學系的首席John Krystal評論,。（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.
