Effects of synaptic plasticity regulated by 17beta-estradiol on learning and memory in rats with Alzheimer's disease

Neurosci Bull. 2010 Apr;26(2):133-9. doi: 10.1007/s12264-010-0913-4.

Abstract

Objective: To investigate whether estrogen modulates learning and memory and long-term potentiation (LTP) in the hippocampus of rats with Alzheimer's disease (AD).

Methods: The rats were divided into ovariectomy (OVX) and estrogen replacement therapy (ERT) groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 microL (10 microg/microL) amyloid-beta peptide 1-40(Abeta1-40) into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively.

Results: The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group (P< 0.05). Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation (HFS), compared with that in OVX group (P< 0.01).

Conclusion: ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.

目的: 探讨雌二醇对阿尔茨海默病(Alzheimer’s disease, AD)大鼠的学习记忆能力及长时程增强(long-term potentiation, LTP)的影响。

方法: 大鼠随机分成卵巢切除 (ovariectomy, OVX)组和雌激素替代治疗(estrogen replace treatment, ERT)组。 两组大鼠均接受卵巢切除手术, ERT组大鼠随后接受雌激素替代治疗。 手术2周后, 两组大鼠海马内立体定位单侧注射1 μL Aβ1–40 (10 μg/μL), 建立AD模型。 运用水迷宫实验检测大鼠的学习和记忆能力, 并进行LTP记录和比较。

结果: OVX组AD大鼠的水迷宫逃避潜伏期相较于ERT组明显延长(P < 0.05)。 此外, 高频刺激(high frequence stimulation, HFS) 30 min后与HFS刺激前相比, ERT组LTP增加的幅值明显高于OVX组(P < 0.05)。

结论: 雌激素替代治疗能改善AD大鼠的认知功能, 调整LTP及突触可塑性。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Animals
  • Disease Models, Animal
  • Estradiol / therapeutic use*
  • Estrogens / therapeutic use*
  • Female
  • Hippocampus / physiopathology
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / etiology
  • Learning Disabilities / pathology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Memory Disorders / pathology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Organ Size / drug effects
  • Ovariectomy
  • Random Allocation
  • Rats
  • Synapses / pathology
  • Synapses / physiology*
  • Uterus / pathology

Substances

  • Estrogens
  • Estradiol