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Aims: 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Locus coeruleus (LC) is considered to be the main source of norepinephrine in the central nervous system (CNS) and plays important role in relieving pain in the body. Changes in the activity of synaptic excitatory amino acid transporters (EAATs) would be an applicable way to regulate synaptic transmission in the LC. In the present study, we examined the role of astrocytic glutamate transporter−1 (GLT1) in the firing activity of LC neurons and the sensation of pain in rats. Male Wistar rats were divided into three control (CNT), ceftriaxone (CFT) and dihydrokainic acid (DHK) groups. Animals were given intraperitoneal injections for nine consecutive days after which the electrophysiological and behavioral experiments were performed to determine the single-unit activity of LC neurons and pain sensation. Results of this study revealed that CFT as a well−known up−regulator of GLT1 expression decreases the latency of pain sensation in rats but inhibition of GLT1 activity by DHK showed no significant effects. Furthermore, the results obtained by single-unit recording from LC showed a significant decrease in evoked response in CFT group compared to the CNT group. Therefore, this study suggests that GLT1 might be considered as a potential therapeutic target for pain modulation in the future. [ABSTRACT FROM AUTHOR]

Highlights • Intracerebroventricular (i.c.v.) injection of okadaic acid (OKA) drastically attenuates fEPSP slope and population spike in hippocampal DG neurons. • Intracerebroventricular injection of OKA significantly decreases the short-term and long-term synaptic plasticity of hippocampal DG neurons. • Administration of OKA results in impaired short-term and long-term spatial memories in rats. Abstract Protein phosphorylation states have a pivotal role in regulation of synaptic plasticity and long-term modulation of synaptic transmission. Serine/threonine protein phosphatase 1 (PP1) and 2A (PP2A) have a critical effect on various regulatory mechanisms involved in synaptic plasticity, learning and memory. Okadaic acid (OKA), a potent inhibitor of PP1 and PP2A, reportedly leads to cognitive decline and Alzheimer's disease (AD)-like pathology. The aim of this study was to examine the effect of OKA on electrophysiological characteristics of hippocampal dentate gyrus (DG) neurons in vivo. Male Wistar rats were divided into two control and OKA groups. OKA was injected intracerebroventricularly (i.c.v.) into lateral ventricles and after two weeks the long-term potentiation (LTP) and paired-pulse responses recorded from hippocampal perforant path-DG synapses in order to assess short-term and long-term synaptic plasticity. Results of this study revealed that OKA-induced inhibition of PP1 and PP2A activity drastically attenuates the field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude following paired pulse and high frequency stimulation (HFS) of hippocampal DG neurons indicating pre- and post-synaptic involvement in electrical activity of these neurons. Administration of OKA impaired the short-term and long-term spatial memories conducted by Y-maze and passive avoidance tests, respectively. OKA-induced attenuation in electrophysiological activity and consequent memory deficits also provide a beneficial tool for studying neurodegenerative disorders such as AD. [ABSTRACT FROM AUTHOR]