1. Effect of ceftriaxone on paired-pulse response and long-term potentiation of hippocampal dentate gyrus neurons in rats with Alzheimer-like disease.
- Author
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Hamidi, Nasrin, Nozad, Abdollah, Sheikhkanloui Milan, Hamid, Salari, Ali-Akbar, and Amani, Mohammad
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CEFTRIAXONE , *DENTATE gyrus , *ALZHEIMER'S disease , *RAT diseases , *NEUROPLASTICITY , *LONG-term potentiation , *NEURONS - 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. 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. 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. Therefore, this study suggests that GLT-1 might be a promising therapeutic target for treatment of neurodegenerative disorders such as AD in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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