Ceftriaxone-mediated upregulation of the glutamate transporter GLT-1 contrasts neurotoxicity evoked by kainate in rat organotypic spinal cord cultures

Bajrektarevic, Dzejla; Nistri, Andrea

doi:10.1016/j.neuro.2017.02.013

Cited by 11 publications

(8 citation statements)

References 49 publications

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“…Importantly, the downregulation of both GLT-1 and GLAST has been observed in paclitaxel-treated [149,162,163], oxaliplatin-treated [164] and bortezomibtreated neuropathic rats [165]. In our recent study [166], a single dose and repeated doses of ceftriaxone, a beta-lactam antibiotic that acts by upregulating GLT-1 expression, thus increasing glutamate reuptake in the CNS [167][168][169], was tested for its ability to attenuate early-phase and late-phase tactile allodynia and cold hyperalgesia in oxaliplatin-treated mice. The repeated intraperitoneal administration of 200 mg/ kg ceftriaxone prevented the development of late-phase tactile allodynia, but ceftriaxone showed no antiallodynic properties in the cold plate test.…”

Section: Central Nervous System Structures and Neurotransmittersmentioning

confidence: 84%

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Sałat

2020

Pharmacol. Rep

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Background Despite the increasing knowledge of the etiology of neuropathic pain, this type of chronic pain is resistant to available analgesics in approximately 50% of patients and therefore is continuously a subject of considerable interest for physiologists, neurologists, medicinal chemists, pharmacologists and others searching for more effective treatment options for this debilitating condition. Materials and methods The present review article is the first of the two articles focused on chemotherapy-induced peripheral neuropathy (CIPN). Results CIPN is regarded as one of the most common drug-induced neuropathies and is highly pharmacoresistant. The lack of efficacious pharmacological methods for treating CIPN and preventing its development makes CIPN-related neuropathic pain a serious therapeutic gap in current medicine and pharmacotherapy. In this paper, the most recent advances in the field of studies on CIPN caused by platinum compounds (namely oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib are summarized. Conclusions The prevalence of CIPN, potential causes, risk factors, symptoms and molecular mechanisms underlying this pharmacoresistant condition are discussed.

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Section: Central Nervous System Structures and Neurotransmittersmentioning

confidence: 84%

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Sałat

2020

Pharmacol. Rep

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“…As glutamate transporters are not enzymes, there are no available agonists capable of enhancing its activity, making it difficult to “synthetically” elicit an increase in glutamate uptake. One way to do it is to treat living mice, brain slices or cultures with ceftriaxone, a beta-lactam antibiotic that enhances GLT-1 expression (Rothstein et al, 2005; Omrani et al, 2009; Bajrektarevic and Nistri, 2017). Chronic ceftriaxone treatment in Wistar rats increased GLT-1 expression, which produced an impairment in LTD in hippocampus mossy fibers CA3 (MF-CA3) synapses (Omrani et al, 2009), an effect reversed by the blockade of GLT-1 with DHK.…”

Section: Glutamate Transporters Impact Within the Synapsementioning

confidence: 99%

Glutamate Transporters in Hippocampal LTD/LTP: Not Just Prevention of Excitotoxicity

Gonçalves-Ribeiro

Pina

Sebastião

et al. 2019

Front. Cell. Neurosci.

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Glutamate uptake is a process mediated by sodium-dependent glutamate transporters, preventing glutamate spillover from the synapse. Typically, astrocytes express higher amounts of glutamate transporters, thus being responsible for most of the glutamate uptake; nevertheless, neurons can also express these transporters, albeit in smaller concentrations. When not regulated, glutamate uptake can lead to neuronal death. Indeed, the majority of the studies regarding glutamate transporters have focused on excitotoxicity and the subsequent neuronal loss. However, later studies have found that glutamate uptake is not a static process, evincing a possible correlation between this phenomenon and the efficiency of synaptic transmission and plasticity. In this review, we will focus on the role of the increase in glutamate uptake that occurs during long-term potentiation (LTP) in the hippocampus, as well as on the impairment of long-term depression (LTD) under the same conditions. The mechanism underpinning the modulatory effect of glutamate transporters over synaptic plasticity still remains unascertained; yet, it appears to have a more prominent effect over the N -methyl- D -aspartate receptor (NMDAR), despite changes in other glutamate receptors may also occur.

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“…Studies with rodents show that ceftriaxone, a beta-lactam antibiotic that increases EAAT2 expression, thus facilitating the removal of free glutamate and preventing glutamatergic excitotoxicity (Hsu et al, 2015), positively regulates EAAT2 acutely and chronically (Rothstein et al, 2005; Szu and Binder, 2016; Zimmer et al, 2017), thus providing neuroprotection under excitotoxic stress conditions. In in vitro models derived from spinal cord cultures, ceftriaxone reduces neuronal loss by increasing EAAT2 expression (Bajrektarevic and Nistri, 2017).…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

“…Bajrektarevic and Nistri (2017) observed that excitotoxic stress induction with 100 μM kainate promotes EAAT2 immunoreactivity in astrocyte cultures pretreated with ceftriaxone for 3 days, suggesting that ceftriaxone confers neuroprotection against an excitotoxic stimulus/challenge when administered prior to treatment with a glutamate uptake inhibitor. In an experimental model of Parkinson’s disease, ceftriaxone has been shown to increase EAAT2 expression in the hippocampus, regardless of whether the treatment started before or after the injury.…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

Role of Glutamatergic Excitotoxicity in Neuromyelitis Optica Spectrum Disorders

Silva

Souza

et al. 2019

Front. Cell. Neurosci.

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Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder mediated by immune-humoral responses directed against central nervous system (CNS) antigens. Most patients are positive for specific immunoglobulin G (IgG) auto-antibodies for aquaporin-4 (AQP4), a water channel present in astrocytes. Antigen-antibody binding promotes complement system cascade activation, immune system cell infiltration, IgG deposition, loss of AQP4 and excitatory amino acid transporter 2 (EAAT2) expression on the astrocytic plasma membrane, triggering necrotic destruction of spinal cord tissue and optic nerves. Astrocytes are very important cells in the CNS and, in addition to supporting other nerve cells, they also regulate cerebral homeostasis and control glutamatergic synapses by modulating neurotransmission in the cleft through the high-affinity glutamate transporters present in their cell membrane. Specific IgG binding to AQP4 in astrocytes blocks protein functions and reduces EAAT2 activity. Once compromised, EAAT2 cannot take up free glutamate from the extracellular space, triggering excitotoxicity in the cells, which is characterized by overactivation of glutamate receptors in postsynaptic neurons. Therefore, the longitudinally extensive myelitis and optic neuritis lesions observed in patients with NMOSD may be the result of primary astrocytic damage triggered by IgG binding to AQP4, which can activate the immune-system cascade and, in addition, downregulate EAAT2. All these processes may explain the destructive lesions in NMOSD secondary to neuroinflammation and glutamatergic excitotoxicity. New or repurposed existing drugs capable of controlling glutamatergic excitotoxicity may provide new therapeutic options to reduce tissue damage and permanent disability after NMOSD attacks.

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Ceftriaxone-mediated upregulation of the glutamate transporter GLT-1 contrasts neurotoxicity evoked by kainate in rat organotypic spinal cord cultures

Cited by 11 publications

References 49 publications

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Glutamate Transporters in Hippocampal LTD/LTP: Not Just Prevention of Excitotoxicity

Role of Glutamatergic Excitotoxicity in Neuromyelitis Optica Spectrum Disorders

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