Effects of neonatal flutamide treatment on hippocampal neurogenesis and synaptogenesis correlate with depression-like behaviors in preadolescent male rats.
Effects of neonatal flutamide treatment on hippocampal neurogenesis and synaptogenesis correlate with depression-like behaviors in preadolescent male rats.
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DOI：
10.1016/j.neuroscience.2010.03.029
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发表时间：
2010-08-11
期刊：
影响因子：
3.3
通讯作者：
McCarthy, M. M.
中科院分区：
文献类型：
--
作者：
Zhang, J. M.;Tonelli, L.;Regenold, W. T.;McCarthy, M. M.
成年男性重度抑郁症（MDD）的患病率大约是女性的一半。临床证据支持雄激素对男性抑郁症的保护作用。发育中的大脑会受到雄激素暴露的影响，但尚未考虑到其在成年期抑郁症中的潜在作用。为了探索这个问题，我们用雄激素受体拮抗剂氟他胺治疗新生雄性大鼠幼崽，以阻断内源性雄激素作用，然后在青春期前进行行为测试。通过强迫游泳测试（FST）和蔗糖偏好测试（SPT）评估抑郁样行为，通过开放场测试（OFT）和新奇抑制喂养测试（NSFT）评估焦虑样行为。与媒介物治疗的对照组相比，新生氟他胺治疗导致青春期前雄性大鼠的抑郁样行为显着增加，但没有引起焦虑样行为的任何显着差异。在单独的实验中，从出生后第 1 天（PND）到第 4 天，接受或未接受氟他胺治疗的雄性幼崽被注射 5-溴-2'-脱氧尿苷-5'-单磷酸（BrdU），以标记新产生的细胞，或者将海马体嵌入高尔基体考克斯并观察锥体神经元。三组证据表明，新生氟他胺治疗可抑制青春期前雄性大鼠的海马神经发生和神经元树突棘形成。与媒介物对照相比，氟他胺治疗显着降低了1）CA1区域中微管相关蛋白2+（MAP-2）神经元的数量，2）海马齿状回（DG）区域中MAP-2+神经元的数量，以及3）CA1区域中锥体神经元树突棘的密度。然而，氟他胺治疗对海马中 GFAP+ 或 GFAP+/BrdU+ 细胞的数量没有影响。这项研究表明雄激素诱导的海马神经发生的组织效应具有抗抑郁作用。
The prevalence of major depressive disorder (MDD) in adult men is roughly half that of women. Clinical evidence supports a protective effect of androgens against depressive disorders in men. The developing brain is subject to androgen exposure but a potential role for this in depression during adulthood has not been considered. In order to explore this question we treated newborn male rat pups with the androgen receptor antagonist flutamide to block endogenous androgen action and then conducted behavioral tests prior to puberty. Depression-like behaviors were assessed with the Forced Swim Test (FST) and the Sucrose Preference Test (SPT), and anxiety-like behaviors were assessed with the Open Field Test (OFT) and the Novelty-Suppressed Feeding Test (NSFT). Compared to the vehicle-treated controls, neonatal-flutamide treatment caused a significant increase in depression-like behaviors in preadolescent male rats but did not cause any significant difference in anxiety-like behaviors. In separate experiments, male pups with and without flutamide treatment were injected with 5-bromo-2’-deoxyuridine-5’-monophosphate (BrdU) from postnatal day (PND) 1 to 4 to label newly produced cells or the hippocampi were Golgi-Cox imbedded and pyramidal neurons visualized. Three lines of evidence indicate neonatal flutamide treatment inhibits hippocampal neurogenesis and neuronal dendritic spine formation in preadolescent male rats. Compared to vehicle controls, flutamide treatment significantly decreased 1) the number of microtubal associated protein-2+ (MAP-2) neurons in the CA1 region, 2) the number of MAP-2+ neurons in the dentate gyrus (DG) region of the hippocampus, and 3) the density of dendritic spines of pyramidal neurons in the CA1 region. However, there was no effect of flutamide treatment on the number of GFAP+ or GFAP+/BrdU+ cells in the hippocampus. This study suggests that the organizational effect of androgen-induced hippocampal neurogenesis is antidepressant.
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影响因子：
16.2
作者：
ALDERSON, RF;ALTERMAN, AL;LINDSAY, RM
通讯作者：
LINDSAY, RM
影响因子：
3.6
作者：
Domínguez-Salazar, E;Camacho, FJ;Paredes, RG
通讯作者：
Paredes, RG
DOI：
10.1016/0022-4731(79)90080-3
发表时间：
1979-01-01
影响因子：
4.1
作者：
FOREST, MG
通讯作者：
FOREST, MG
影响因子：
4.1
作者：
BINGAMAN, EW;MAGNUSON, DJ;HANDA, RJ
通讯作者：
HANDA, RJ
影响因子：
3.6
作者：
BRITTON, DR;BRITTON, KT
通讯作者：
BRITTON, KT