Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.
Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.
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DOI：
10.3389/fncel.2013.00066
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发表时间：
2013
影响因子：
5.3
通讯作者：
Wyneken U
中科院分区：
文献类型：
--
作者：
Rubio FJ;Ampuero E;Sandoval R;Toledo J;Pancetti F;Wyneken U
抗抑郁药物通常服用数周来治疗重度抑郁症。然而，它们也被用于治疗几种其他精神疾病以及长期维持治疗。抗抑郁药会引起几种前脑结构的适应性变化，其中包括谷氨酸能突触的改变。我们最近发现，对幼稚的成年雄性大鼠重复施用选择性血清素再摄取抑制剂（SSRI）氟西汀可诱导几个前脑区域成熟的蘑菇型树突棘的增加。这与端脑突触后密度中含有 GluA2 的 α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯受体 (AMPA-R) 的增加有关。为了揭示这种突触重新排列的功能意义，我们重点关注海马体中的谷氨酸神经传递。我们评估了 4 周 0.7 mg/kg 氟西汀对 CA1 海马亚区长时程增强 (LTP) 和长期抑制 (LTD) 的影响。海马切片的记录显示，Schaffer 侧支 CA1 突触的 LTP 和 LTD 存在严重缺陷，这与棘密度增加和蘑菇型棘的存在增强有关，正如高尔基体染色所显示的那样。然而，相同的治疗既不影响脊柱形态，也不影响穿通路径-CA1 突触的 LTP 和 LTD。钴染色和免疫组织化学实验显示，放射层 (s.r.) 中 AMPA-R Ca2+ 通透性降低，同时含有 GluA2 的 Ca2+ 不通透性 AMPA-R 增加。因此，4周的氟西汀治疗以通路特异性方式促进CA1神经元的结构和功能适应，选择性地与Schaffer侧支CA1突触的活动依赖性可塑性受损相关。
Antidepressant drugs are usually administered for several weeks for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long-term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine to naïve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs) in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of 0.7 mg/kg fluoxetine on long-term potentiation (LTP) and long-term depression (LTD) in the CA1 hippocampal subfield. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining and immunohistochemical experiments revealed decreased AMPA-R Ca2+ permeability in the stratum radiatum (s.r.) together with increased GluA2-containing Ca2+ impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.
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DOI：
10.1126/science.1214592
发表时间：
2011-12-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Karpova NN;Pickenhagen A;Lindholm J;Tiraboschi E;Kulesskaya N;Agústsdóttir A;Antila H;Popova D;Akamine Y;Bahi A;Sullivan R;Hen R;Drew LJ;Castrén E
通讯作者：
Castrén E
影响因子：
3.3
作者：
Ampuero, E.;Rubio, F. J.;Wyneken, U.
通讯作者：
Wyneken, U.
影响因子：
4.2
作者：
Barbon, Alessandro;Caracciolo, Luca;Barlati, Sergio
通讯作者：
Barlati, Sergio
影响因子：
3.1
作者：
First, Maya;Gil-Ad, Irit;Weizman, Abraham
通讯作者：
Weizman, Abraham
影响因子：
2.5
作者：
Corvin, Aiden P.;Molinos, Ines;Tropea, Daniela
通讯作者：
Tropea, Daniela