اثر سفتریاکسون بر پاسخ زوج‌-تحریک و تقویت طولانی مدت نورونهای شکنج دندانه دار هیپوکامپ در موش های مدل آلزایمری

حمیدی, نسرین and نوزاد, عبدالله and شیخکانلوی میلان, حمید and سالاری, علی اکبر and امانی, محمد (1398) اثر سفتریاکسون بر پاسخ زوج‌-تحریک و تقویت طولانی مدت نورونهای شکنج دندانه دار هیپوکامپ در موش های مدل آلزایمری. Life sciences ــ 238 (116969). pp. 1-9. شاپا 0024-3205

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Effect of ceftriaxone on paired-pulse response and long-term potentiation of hippocampal dentate gyrus neurons in rats with Alzheimer-like disease

English Abstract

Glutamatergic dysfunction is posed as a main stage in neurodegenerative disorders such as Alzheimer's disease (AD). Glutamate-mediated excitotoxicity contributes to cognitive dysfunction and cell death in AD. Ceftriaxone (CFT), a well-known upregulator of GLT-1, selectively induces the expression of glutamate transporter-1 (GLT-1) in different brain regions and therefore can be posed as a potential candidate for elimination of glutamate-induced excitotoxicity which is an early prominent event in AD brains. This study was designed to investigate the electrophysiological and behavioral effects of the β-lactam antibiotic ceftriaxone in okadaic acid (OKA)-induced model of AD. MATERIALS AND METHODS: Male Wistar rats divided into four control, ceftriaxone (CFT), OKA, and OKA plus ceftriaxone (OKA + CFT) groups. OKA was injected intracerebroventricularly (i.c.v., 200 ng/5 μl) into lateral ventricles and after two weeks the evoked field potential recorded from hippocampal perforant path-DG synapses in order to evaluate the effect of ceftriaxone treatment (200 mg/kg/day, i.p.) on long-term potentiation (LTP) and paired-pulse responses. KEY FINDINGS: Results of this study revealed that ceftriaxone treatment significantly ameliorates the OKA-induced attenuation of field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude following high-frequency stimulation and paired-pulse paradigm indicating its beneficial effects on both short-term and long-term plasticity in these neurons. Ceftriaxone also has an improving effect on OKA-induced impairment in short- and long-term memories evaluated by alternation behavior and passive avoidance tasks in rats. SIGNIFICANCE: Therefore, this study suggests that GLT-1 might be a promising therapeutic target for treatment of neurodegenerative disorders such as AD in the future.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نسرین حمیدی
نویسنده :عبدالله نوزاد
نویسنده :حمید شیخکانلوی میلان
نویسنده :علی اکبر سالاری
نویسنده مسئول :محمد امانی
Additional Information:IF: 3.448 Indexed in: ISI, PubMed/Medline, Scopus, Embase
کلیدواژه ها (انگلیسی):lzheimer's disease; Ceftriaxone; Dentate gyrus; Okadaic acid; Synaptic plasticity
Subjects:QT physiology
WL Nervous system
Divisions:Faculty of Medicine > Department of Basic Sciences > Department of physiology
ID Code:12396
Deposited By: Dr Hamid Sheikhkanloui Milan
Deposited On:20 Aug 1398 10:56
Last Modified:20 Aug 1398 10:56

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