Investigating the Impact of Intracerebroventricular Streptozotocin on Female Rats with and without Ovaries: Implications for Alzheimer’s Disease

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemical Research Pub Date : 2024-07-10 DOI:10.1007/s11064-024-04204-x
Juliette López Hanotte, Facundo Peralta, Paula Cecilia Reggiani, María Florencia Zappa Villar
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Abstract

To contribute to research on female models of Alzheimer’s disease (AD), our aim was to study the effect of intracerebroventricular (ICV) injection of streptozotocin (STZ) in female rats, and to evaluate a potential neuroprotective action of ovarian steroids against STZ. Female rats were either ovariectomized (OVX) or kept with ovaries (Sham) two weeks before ICV injections. Animals were injected with either vehicle (artificial cerebrospinal fluid, aCSF) or STZ (3 mg/kg) and separated into four experimental groups: Sham + aCSF, Sham + STZ, OVX + aCSF and OVX + STZ. Nineteen days post-injection, we assessed different behavioral aspects: burying, anxiety and exploration, object recognition memory, spatial memory, and depressive-like behavior. Immunohistochemistry and Immunoblot analyses were performed in the hippocampus to examine changes in AD-related proteins and neuronal and microglial populations. STZ affected burying and exploratory behavior depending on ovarian status, and impaired recognition but not spatial memory. STZ and ovariectomy increased depressive-like behavior. Interestingly, STZ did not alter the expression of β-amyloid peptide or Tau phosphorylated forms. STZ affected the neuronal population from the Dentate Gyrus, where immature neurons were more vulnerable to STZ in OVX rats. Regarding microglia, STZ increased reactive cells, and the OVX + STZ group showed an increase in the total cell number. In sum, STZ partially affected female rats, compared to what was previously reported for males. Although AD is more frequent in women, reports about the effect of ICV-STZ in female rats are scarce. Our work highlights the need to deepen into the effects of STZ in the female brain and study possible sex differences.

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研究脑室内注射链脲佐菌素对有卵巢和无卵巢雌性大鼠的影响:对阿尔茨海默病的影响
为了促进阿尔茨海默病(AD)雌性模型的研究,我们的目的是研究雌性大鼠脑室内注射链脲佐菌素(STZ)的影响,并评估卵巢类固醇对 STZ 的潜在神经保护作用。雌性大鼠在接受 ICV 注射前两周被切除卵巢(OVX)或保留卵巢(Sham)。给大鼠注射载体(人工脑脊液)或 STZ(3 毫克/千克),并将其分为四个实验组:Sham + aCSF、Sham + STZ、OVX + aCSF 和 OVX + STZ。注射后19天,我们对不同的行为进行了评估:埋葬、焦虑和探索、物体识别记忆、空间记忆和抑郁样行为。我们对海马进行了免疫组化和免疫印迹分析,以检测与AD相关的蛋白质以及神经元和小胶质细胞群的变化。STZ会影响埋藏和探索行为,这取决于卵巢状态,并且会损害识别能力,但不会损害空间记忆。STZ和卵巢切除术增加了抑郁样行为。有趣的是,STZ并未改变β-淀粉样肽或Tau磷酸化形式的表达。STZ影响了齿状回的神经元群,在OVX大鼠中,未成熟的神经元更容易受到STZ的影响。在小胶质细胞方面,STZ 增加了反应性细胞,OVX + STZ 组显示细胞总数增加。总之,STZ 对雌性大鼠产生了部分影响,而之前的报告显示对雄性大鼠产生了影响。虽然注意力缺失症在女性中更为常见,但有关 ICV-STZ 对雌性大鼠影响的报道却很少。我们的研究突出表明,有必要深入研究 STZ 对雌性大鼠大脑的影响,并研究可能存在的性别差异。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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