Orexin/hypocretin treatment restores hippocampal-dependent memory in orexin-deficient mice.
Orexin/hypocretin treatment restores hippocampal-dependent memory in orexin-deficient mice.
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DOI：
10.1016/j.nlm.2017.10.014
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发表时间：
2017-12
影响因子：
2.7
通讯作者：
Kotz CM
中科院分区：
文献类型：
--
作者：
Mavanji V;Butterick TA;Duffy CM;Nixon JP;Billington CJ;Kotz CM
食欲素A在下丘脑外侧区的外侧、穹窿周围和背内侧区域的神经元中产生，然后广泛投射到整个中枢神经系统以调节唤醒状态、睡眠-觉醒结构、能量稳态和认知过程。食欲素信号传导的中断导致睡眠障碍和体重指数增加，但最近的研究也表明食欲素神经元激活可以改善学习和记忆。我们假设海马食欲素受体激活提高记忆力。为了验证这个想法，我们获得了食欲素/共济失调蛋白-3（O/A3）小鼠，它们在大约12周龄时缺乏食欲素神经元。我们首先测量了海马食欲素受体1（OX 1 R）基因表达和蛋白水平，然后测试了双向主动回避（TWAA）记忆的获得和巩固，这是一种依赖于海马的学习和记忆任务。最后，我们确定了外源性海马内OXA治疗是否可以逆转OA/3小鼠的认知障碍（如通过TWAA所确定的）。我们发现，OX 1 R mRNA表达和蛋白水平显着升高O/A3小鼠，表明保留食欲素反应的潜力。与对照小鼠相比，0/A3小鼠在TWAA记忆中显著受损，但OXA治疗（急性和慢性）逆转了这些记忆缺陷。这些结果表明，食欲素在双向主动回避记忆的海马依赖性巩固过程中起重要作用，食欲素替代可以挽救认知障碍。
Orexin A is produced in neurons of the lateral, perifornical and dorsomedial regions of the lateral hypothalamic area, which then project widely throughout the central nervous system to regulate arousal state, sleep-wake architecture, energy homeostasis and cognitive processes. Disruption of orexin signaling leads to sleep disturbances and increased body mass index, but recent studies also indicate that orexin neuron activation improves learning and memory. We hypothesized that hippocampal orexin receptor activation improves memory. To test this idea, we obtained orexin/ataxin-3 (O/A3) mice, which become deficient in orexin neurons by about 12 weeks of age. We first measured hippocampal orexin receptor 1 (OX1R) gene expression and protein levels, then tested acquisition and consolidation of two-way active avoidance (TWAA) memory, a hippocampal-dependent learning and memory task. Finally, we determined if exogenous intra-hippocampal OXA treatment could reverse cognitive impairment (as determined by TWAA) in OA/3 mice. We showed that OX1R mRNA expression and protein levels were significantly elevated in O/A3 mice, indicating the potential for preserved orexin responsiveness. The O/A3 mice were significantly impaired in TWAA memory vs. control mice, but OXA treatment (both acute and chronic) reversed these memory deficits. These results demonstrate that orexin plays an important role in hippocampal-dependent consolidation of two-way active avoidance memory, and orexin replacement can rescue the cognitive impairment.
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影响因子：
14.5
作者：
Fronczek, Rolf;Overeem, Sebastiaan;Swaab, Dick F.
通讯作者：
Swaab, Dick F.
影响因子：
64.5
作者：
BOURTCHULADZE, R;FRENGUELLI, B;SILVA, AJ
通讯作者：
SILVA, AJ
影响因子：
3.7
作者：
Guo, Yang;Feng, Pingfu
通讯作者：
Feng, Pingfu
影响因子：
3
作者：
Akbari, Esmaeil;Naghdi, Nasser;Motamedi, Fereshteh
通讯作者：
Motamedi, Fereshteh
DOI：
10.1111/j.1749-6632.2012.06585.x
发表时间：
2012-01-01
期刊：
BRAIN AND OBESITY
影响因子：
--
作者：
Kotz, Catherine;Nixon, Joshua;Billington, Charles
通讯作者：
Billington, Charles