Search

Introduction: Cisplatin is one of the most commonly used antineoplastic drugs; nonetheless, its ototoxic dose-limiting side effects have remained a significant challenge in clinical practice. The recognition of the exact template of hearing loss induced by multiple low doses of cisplatin could be of great help in managing the treatment process. The present study aimed to investigate the effects of multiple doses of this drug on the auditory system. Material and Methods: The present study was performed using an experimental guinea pig model in four groups as follows: 1- 0.9% sodium chloride solution, 2- total dose of 7.5 mg/kg Cisplatin, 3- total dose of 10 mg/kg Cisplatin, and 4- total dose of 12.5 mg/kg cisplatin. The drugs were injected as 2.5 mg/kg/daily IP access in all groups. The auditory brainstem response (ABR) test was performed before the treatment and after every injection on a daily basis up to 72 h after the last injection. Results: There was dose-dependent significant hearing loss in all evaluated frequencies in three cisplatin groups. The general template of induced hearing loss during experimental days was almost the same in groups Cis7.5 and Cis10. In Cis 12.5 group, there was a jump in the threshold shift on the 5th day of the experiment and an upward trend in the function. Conclusion: As evidenced by the obtained results, the monitoring of hearing loss after every injection in patients who receive the drug and detecting the exact dose-dependent pattern of the induced hearing loss is of great help in controlling its undesirable destructive side effects on the auditory system.

Alzheimer’s disease (AD) is undoubtedly one of the serious and growing public health challenges in the world today. There is an unmet need for new and effective preventative and therapeutic treatment approaches for AD, particularly at early stages of the disease. However, the underlying mechanism against Aβ-induced electrophysiological alteration in cultured hippocampal pyramidal neurons is still not fully understood. This study investigated the impacts of activation and inhibition of PPAR-γ/δ on the Aβ-induced functional toxicity, which occured before cell death, using patch clamp technique. Findings demonstrated that Aβ treatment alone altered the normal electrophysiological properties and reduced the Ca2+ channel currents in primary cultured hippocampal pyramidal neurons without any major changes either in cell structure, as evidenced by electron microscope examination, or cell viability. Rosiglitazone (30 µM), a potent PPAR-γ activator, when co-treated with Aβ (100 nM) prevented almost completely the induction of function toxicity of Aβ, as evidentiated by restored normal appearing electrophysiological properties. Inhibition of PPAR- γ/δ by FH535 (15 µM), an inhibitor of both Wnt/beta-catenin signaling and PPAR- γ and δ activity, when applied in combination of Aβ not only worsen the toxic electrophysiological effects of Aβ on firing frequency, membrane resistance and cell viability, but also even preserved the suppressive effect of Aβ on Ca2+ channel current when compared to control condition. Overall, these findings suggest that PPAR-γ activation could be a potential candidate to prevent the functional changes induced by low concentration of Aβ which may possibly occur in neurons during early stages of AD.

It has been shown that brain glucose metabolism impairment, obesity, and diabetes could lead to cognitive decline and Alzheimer's disease (AD) pathogenesis. Kisspeptin (KP) a G-protein coupled receptor neuropeptide, has been suggested as a link between energy balance and reproduction. Some studies have shown that the attenuation of KP signaling decreases metabolism and energy expenditure. KP mRNAs and receptors are detected in the hippocampus and cause the promotion of excitatory synaptic responses through modulation of postsynaptic signaling. The purpose of this study was to investigate the effect of KP on spatial learning and memory and its possible neuroprotective effect on Amyloid-Beta induced cognitive impairment using the Morris Water Maze (MWM) task in rats. The reference and reversal spatial learning and memory have been measured in this study. Rats were injected bilaterally by Aβ1-42 (2 μg/μL) or saline as a vehicle into the hippocampal CA1 area. One week later, KP-13 (1.5 or 2 µg/µL) was injected i.c.v before or after each training session for 3 days and memory was tested 24 h later. The results showed KP-13 by itself could significantly enhance spatial memory consolidation and retrieval, and Aβ induced reversal and reference memory impairment was significantly ameliorated by KP-13. In Conclusion, it seems that KP-13 as a neuropeptide has to enhance spatial memory properties and could be a possible neuroprotective peptide on amyloid-beta induced pathology.

Epilepsy is a chronic neurological disease which disrupts the neuronal electrical activity. One-third of patients are resistant to treatment with available antiepileptic agents. The use of herbal medicine for treating several diseases including epilepsy is on the rise. Therefore, further investigation is required to verify the safety and effectiveness of Phytomedicine in treating diseases. The current study is an attempt to elucidate the electrophysiological mechanism of the effect of Dorema ammoniacum gum on a cellular model of epilepsy, using intracellular recording method. The gum was applied either after or before pentylenetetrazole, as an epileptic drug, in order to explore the possible therapeutic and preventive effects of gum. Treatment with D. ammoniacum gum alone increased the neuronal excitability and when applied before or after treatment with PTZ not only did not prevent or change the electrophysiological changes induced by PTZ but also re-enhanced the induction of hyperexcitability and epileptiform activity through depolarizing membrane potential, increasing the firing frequency and decreasing the AHP amplitude. However, phenobarbital, as a standard anti-epileptic agent, almost reversed the effect of PTZ and preserved the normal firing properties of F1 neurons. The possible candidate mechanism of the effect of gum on neuronal excitability could be suppressive effects of gum on voltage and/or Ca2+ dependent K+ channels currents underlying AHP.

Despite the consensus that neuro-inflammation and insulin resistance (IR) are two hallmarks of Alzheimer disease (AD), the molecular mechanisms responsible for the development of IR remain uncharacterized. MAPKs are signaling molecules that are implicated in the pathology of AD and have a role in IR development. Given that inflammatory mediators are shown to interfere with insulin signaling pathway in different cell types, the present work aimed to investigate whether neuro-inflammation induced memory loss is associated with hippocampal IR and whether insulin treatment protects against this IR. Subsequently, possible roles of MAPKs in this situation were investigated. Male Wistar rats were cannulated, and LPS (15 μg, day 0), insulin (3 mU) or saline (vehicle) were administered intra-cerebroventricularly (ICV) (days 1-6). Spatial memory performance was assessed during days 7-10 by Morris Water Maze test. Consequently, analysis of the amount of hippocampal phosphorylated forms of P38, JNK, ERK, IRS1 (ser307) and Akt (ser473) were done by Western blot. The outcomes indicated that while LPS induced memory loss and hippocampal IR (shown by elevated IRS1 and decreased Akt phosphorylation),insulin treatment nullified these effects. Molecular results also showed that LPS mediated IR and memory loss are associated with P38 but not JNK and ERK activation; this P38 activation was reversed by insulin treatment. These observations implied that one of the ways by which neuro-inflammation participates in AD is via induction of IR. It seems that this IR is mainly mediated by P38. Therefore, P38 could be considered as a molecular target for preventing IR development., EXCLI Journal;Vol. 17 2018