It has been postulated that hyperactive glycogen synthase kinase-3 (GSK-3) is an important factor in the pathogenesis of depression, and that this enzyme also contributes to the mechanism of antidepressant drug action. In the present study, we investigated the effect of prenatal stress (an animal model of depression) and long-term treatment with antidepressant drugs on the concentration of GSK-3beta and its main regulating protein kinase B (PKB, Akt). The concentration of GSK-3beta, its inactive form (phospho-Ser9-GSK-3beta), and the amounts of active (phospho-Akt) and total Akt were determined in the hippocampus and frontal cortex in rats. In order to verify our animal model of depression, immobility time in the forced swim test (Porsolt test) was also determined.We found that prenatally stressed rats display a high level of immobility in the Porsolt test and chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine normalize this change. Western blot analysis demonstrated that GSK-3beta levels were significantly elevated in the frontal cortex, but not in the hippocampus, of prenatally stressed rats. The concentration of its non-active form (phospho-Ser9-GSK-3beta) was decreased only in the former brain structure. No changes were found in the amounts of active (phospho-Akt) and total Akt in both studied brain structures. Chronic treatment with antidepressant drugs diminished stress-induced alterations in GSK-3beta and phospho-GSK-3beta the frontal cortex, but had no effect on the concentration of these enzymes in the hippocampus. Moreover, levels of Akt and phospho-Akt in all experimental groups remained unchanged. Since our animal model of depression is connected with hyperactivity of the HPA axis, our results suggest that GSK-3beta is an important intracellular target for maladaptive glucocorticoid action on frontal cortex neurons and in antidepressant drug effects. Furthermore, the influence of stress and antidepressant drugs on GSK-3beta does not appear to impact the kinase activity of Akt.

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Background : At least 20 -30% of epileptic patients do not sufficiently respond to monotherapy. Some of them can benefit from drug combinations; hence, animal data may provide some useful novel clues for rational polytherapy. Objective : To review combinations of antiepileptic drugs, evaluated with the help of isobolographic analysis, in terms of their efficacy and adverse effects. Methods : A literature search, on the basis of experimental studies, with no time limit was carried out. Results/conclusion : Preclinical data indicate that a synergy occurred for the combinations of valproate + phenytoin, valproate + ethosuximide, lamotrigine + valproate, gabapentin + valproate, gabapentin + carbamazepine, topiramate + carbamazepine, topiramate + valproate, topiramate + oxcarbazepine, levetiracetam + topiramate, levetiracetam + oxcarbazepine, oxcarbazepine + gabapentin, tiagabine + gabapentin and lamotrigine + topiramate. On the other hand, lamotrigine combined with carbamazepine or oxcarbazepine resulted in a clear-cut antagonism. Interestingly, a combination of oxcarbazepine + clonazepam produced variable responses, including synergy, additivity or antagonism, depending on the dose ratio of these drugs. In no case did pharmacokinetic factors contribute to the final analysis of the effects of drug combinations. Pharmacokinetic factors can contribute to the final effect of drug combinations, such as when stiripentol is added to valproate, or clobazam is added to valproate. It may be concluded that the rational treatment of drug-resistant epilepsy needs to consider the results of preclinical studies.

Absence seizures are generalized nonmotor epileptic seizures with abrupt onset and termination. Transient impairment of consciousness and spike-slow wave discharges (SWDs) in EEG are their characteristic manifestations. This type of seizure is severe in two common pediatric syndromes: childhood (CAE) and juvenile (JAE) absence epilepsy. The appearance of low-cost, portable EEG devices has paved the way for long-term, remote monitoring of CAE and JAE patients. The potential benefits of this kind of monitoring include facilitating diagnosis, personalized drug titration, and determining the duration of pharmacotherapy. Herein, we present a novel absence detection algorithm based on the properties of the complex Morlet continuous wavelet transform of SWDs. We used a dataset containing EEGs from 64 patients (37 h of recordings with almost 400 seizures) and 30 age and sex-matched controls (9 h of recordings) for development and testing. For seizures lasting longer than 2 s, the detector, which analyzed two bipolar EEG channels (Fp1-T3 and Fp2-T4), achieved a sensitivity of 97.6% with 0.7/h detection rate. In the patients, all false detections were associated with epileptiform discharges, which did not yield clinical manifestations. When the duration threshold was raised to 3 s, the false detection rate fell to 0.5/h. The overlap of automatically detected seizures with the actual seizures was equal to ~96%. For EEG recordings sampled at 250 Hz, the one-channel processing speed for midrange smartphones running Android 10 (about 0.2 s per 1 min of EEG) was high enough for real-time seizure detection.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with one of the highest survival rates. Long-term complications that occur after intensive oncological treatment often impair normal daily functioning. However, existing data on peripheral nervous system condition in ALL survivors remain conflicting.Materials and Methods: The study group consisted of 215 ALL survivors. Patients were treated with New York (NY, n = 45), previous modified Berlin–Frankfurt–Münster (pBFM, n = 64), and BFM95 (n = 106) protocols. Time elapsed between the end of the treatment and the control examination varied from 0.3 to 20.9 years. The analyzed patients underwent a neurophysiological analysis with electroneurography (ENG) of motor (median and peroneal) and sensory (median and sural) nerves as well as electromyography (EMG) of tibialis anterior, vastus lateralis, and interosseous I muscles. To estimate the influence of radiotherapy on recorded neurophysiological responses, a joint analysis of NY, and pBFM groups was performed.Results: Clinical symptoms of polyneuropathy were noted among 102 (47.4%) children during the ALL therapy and in 111 (51.6%) during follow-up. At the time of treatment, polyneuropathy was diagnosed in 57.8% participants from NY group, 35.9%—pBFM and 50.0%—BFM95 (p = 0.145). A significantly higher incidence of polyneuropathy was observed during a follow-up in the NY group (68.9%; p < 0.001 vs. pBFM, p = 0.002 vs. BFM95). The most frequent abnormality within all the protocols was demyelination (NY: 44.4%, pBFM: 59.4%, BFM95: 41.5%), in contrast to the least frequently registered isolated axonal changes. The negative influence of oncological treatment on neurophysiological parameters in ALL survivors was observed. Complex disorders of motor nerves, sensory nerves, and motor unit potentials were registered. Motor-sensory neuropathy was the most frequently found pathology in all analyzed protocols. The harmful effect of radiotherapy was also observed in EMG results.Conclusions: Detailed neurophysiological analysis in long-term childhood ALL survivors has shown generalized abnormalities in registered parameters. To our knowledge, the current study is the largest and one of the most comprehensive ones among those examining disturbances in ENG and EMG in this group of patients. Moreover, we are the first ones to demonstrate the negative influence of radiotherapy on peripheral nerve conduction parameters.