Scholarlink

<p>Alzheimer’s disease (AD) is characterized by cognitive deterioration, oxidative stress and neuroinflammation. Reliable preclinical models for sporadic AD are lacking. The intracerebroventricular (ICV) streptozotocin (STZ) model simulates pathology of sporadic AD; its timeline remains ambiguous. We assessed multiple endpoints in male Wistar rats 1 and 3 months post-ICV STZ (3&#xa0;mg/kg; <i>n</i> = 72; control, sham, STZ). Spatial and associative memory was tested via the Morris Water Maze and Passive Avoidance Task. Hippocampal superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF) were measured by ELISA; neuronal integrity and amyloid deposits by hematoxylin–eosin (H&amp;E) and Congo red staining. STZ groups (3-months vs. 1-month) exhibited cognitive deficits: increased escape latency (80.14 ± 5.75 vs. 65.68 ± 11.51&#xa0;s; <i>P</i> = 0.008), decreased time in the target quadrant (7.32 ± 0.71 vs. 11.6 ± 1.99&#xa0;s; <i>P</i> = 0.019), platform crossings (0.83 ± 0.4 vs. 2.5 ± 0.83; <i>P</i> &lt; 0.001) and step-through latency (3.89 ± 1.14 vs. 12.43 ± 3.28&#xa0;s; <i>P</i> = 0.011). SOD activity decreased (6.28 ± 0.76 vs. 10.11 ± 1.26 U/mg; <i>P</i> = 0.015), TNF-α increased (71.17 ± 2.16 vs. 58.06 ± 2.22 pg/mg; <i>P</i> = 0.004) and BDNF declined (47.09 ± 9.21 vs. 86.83 ± 8.51 pg/mg; <i>P</i> &lt; 0.001). Histology revealed neuronal shrinkage, vacuolation and amyloid deposits in 3-months STZ rats. The ICV STZ model recapitulates AD features: cognitive decline, oxidative stress, neuroinflammation and compromised neurotrophic support. Limitations such as lack of neurofibrillary tangles and sex evaluations require investigation. Studies exploring tau pathology, sex differences, and long-term dynamics may refine therapeutic strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Multidimensional Evaluation of the Streptozotocin-Induced Alzheimer’s Model: Integrating Molecular, Histopathological, and Behavioral Correlates Over Time

  • 期刊论文

  • 发表日期：

    2025年6月27日

查看全文
  • Amir Bavafa,
  • Gholam Hossein Meftahi,
  • Gila Pirzad Jahromi

摘要

Alzheimer’s disease (AD) is characterized by cognitive deterioration, oxidative stress and neuroinflammation. Reliable preclinical models for sporadic AD are lacking. The intracerebroventricular (ICV) streptozotocin (STZ) model simulates pathology of sporadic AD; its timeline remains ambiguous. We assessed multiple endpoints in male Wistar rats 1 and 3 months post-ICV STZ (3 mg/kg; n = 72; control, sham, STZ). Spatial and associative memory was tested via the Morris Water Maze and Passive Avoidance Task. Hippocampal superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF) were measured by ELISA; neuronal integrity and amyloid deposits by hematoxylin–eosin (H&E) and Congo red staining. STZ groups (3-months vs. 1-month) exhibited cognitive deficits: increased escape latency (80.14 ± 5.75 vs. 65.68 ± 11.51 s; P = 0.008), decreased time in the target quadrant (7.32 ± 0.71 vs. 11.6 ± 1.99 s; P = 0.019), platform crossings (0.83 ± 0.4 vs. 2.5 ± 0.83; P < 0.001) and step-through latency (3.89 ± 1.14 vs. 12.43 ± 3.28 s; P = 0.011). SOD activity decreased (6.28 ± 0.76 vs. 10.11 ± 1.26 U/mg; P = 0.015), TNF-α increased (71.17 ± 2.16 vs. 58.06 ± 2.22 pg/mg; P = 0.004) and BDNF declined (47.09 ± 9.21 vs. 86.83 ± 8.51 pg/mg; P < 0.001). Histology revealed neuronal shrinkage, vacuolation and amyloid deposits in 3-months STZ rats. The ICV STZ model recapitulates AD features: cognitive decline, oxidative stress, neuroinflammation and compromised neurotrophic support. Limitations such as lack of neurofibrillary tangles and sex evaluations require investigation. Studies exploring tau pathology, sex differences, and long-term dynamics may refine therapeutic strategies.