Opera Medica et Physiologica

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Printed March 29, 2018;
Published ahead of print April 02, 2018; Printed March 29, 2018; OM&P 2018 Volume 4 Issue 1, pages 1-18; doi:10.20388/omp2018.001.0053
Abstract Full Text

Ionic homeostasis in the brain involves redistribution of ionic fluxes in several cell types and compartments, including neurons, astrocytes and the extracellular space. How the major ionic activity-dependent fluxes of potassium and sodium are individually regulated remains difficult to dissociate and to track experimentally. We here review recent progress in modeling the ionic fluxes evoked by neuronal activity based on mass conservation. Excitability of neurons indeed relies on inward sodium and outward potassium fluxes during action potential firing. Recently, we have developed a tri-compartment model based on mass-action kinetics equations that account for potassium dynamics between neurons, astrocytes and the extracellular space. This review describes how such type of model can be used to spatially and temporally predict potassium fluxes during various regimes of neuronal activity. In particular, the model initially showed that it takes several seconds for astrocytes to buffer the majority of the potassium rapidly released by neurons in both basal and high regime of activity. Such model can also probe the selective contribution of ionic channels, and revealed for instance that disruption of the main astroglial potassium Kir4.1 channels not only favors the emergence of epileptiform activity, but also dysregulates neuronal excitability specifically during slow rhythmic activities. We here also extend the predictions of the model by assessing the selective contribution of the astroglial and neuronal Na/K ATPase, or volume of the extracellular space on potassium dynamics. We discuss these findings and their implications for neuronal information processing in the healthy and diseased brain.

 

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Printed March 29, 2018;
Published ahead of print March 29, 2018; Printed March 29, 2018; OM&P 2018 Volume 4 Issue 1, pages 23-34; doi:10.20388/omp2018.001.0055
Abstract Full Text

The goal of the work was to study the effect of the cannabinoid receptor agonist WIN55,212-2 and the cannabinoid type 1 receptor antagonist AM251 on electrophysiological changes in the hippocampus and the medial septal region (MS) induced by the intracerebral administration of excitotoxin kainic acid. Kainate injected into the right brain ventricle provoked persistent seizures (status epilepticus, SE) in all rats. A morphological analysis of the right hippocampus performed one month after the SE revealed the death of neurons, which was most pronounced in the hilus of the dentate gyrus and in the CA3a field of the dorsal hippocampus. In brain slices taken one month after the SE, the spontaneous activity of MS neurons and population EPSP (pEPSP) in the CA1 field of the hippocampus evoked by the stimulation of Shaffer collaterals (SC) was recorded; the changes in the activity were compared with the activity in slices of healthy animals injected with normal saline (“control slices”). It was found that the activity in MS slices from the brain of animals injected with kainic acid (“kainate slices”) was almost twice higher than in the control. After the application of WIN55,212-2, the frequency of discharges in the control did not change, whereas in kainate slices, the level of neuronal activity decreased to the control value. The application of AM251 led to an increase in the frequency of discharges in the control and its decrease in kainate slices. The registration of pEPSPs in the hippocampal slices revealed a twofold increase in the responses to SC stimulation in kainate slices compared with those in the control, i.e., an abrupt increase in neuronal excitability. A tendency for a decrease in excitability after the application of WIN55,212-2 and, conversely, for its increase by the action of AM251 was noted in evoked responses in the hippocampal kainate slices. Our results allow to assume the protective impact of cannabinoid agonist WIN55,212-2 on neuronal activity in the medial septum and hippocampus that disturbed by neurotoxic kainate influence. 

 

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Printed March 29, 2018;
Published ahead of print March 29, 2018; Printed March 29, 2018; OM&P 2018 Volume 4 Issue 1, pages 19-22; doi:10.20388/omp2018.001.0054
Abstract Full Text

Сlassical bioindicators – amphibians – were used to assess the quality of the environment and detect cytogenetic disorders. There are immature erythrocytes with rounded micronuclei in the bone marrow cells. The merging and transformation of micronuclei occurs in the process of mitotic division and erythrocytes maturing. It leads to a prepotency in the bloodstream of erythrocytes with disintegrated micronuclei and an attached micronucleus. An integrated research study of the environment using the cytogenetic characteristics of living organisms is called for.

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Printed December 25, 2017;
Published ahead of print December 28, 2017; Printed December 25, 2017; OM&P 2017 Volume 3 Issue 3, 4, pages 93-98; doi:10.20388/omp2017.003.0050
Abstract Full Text

Synchrony in neuronal networks plays a crucial role in the functioning of the brain. Stability of synchrony is most desirable to prevent any emergent desynchrony due to natural events, internal or external disturbances. The brain might have its own mechanism to repair its desynchrony, otherwise, some external procedure might be necessary to restore synchrony. We propose here a mechanism to realize robust synchrony in neuronal networks against parameter drifting. A selective addition of cross-coupling links over and above the conventional diffusive coupling links is found [Saha et al. (2017)] recently that makes dramatic improvements in the stability of synchrony of dynamical networks and that saves synchrony against breakdown due to parameter drifting. We apply the concept to realize globally stable synchrony in neuronal networks and the desired effect of robust synchrony and, present our numerical studies with examples of network motifs and a larger network of neurons and using the Hindmarsh-Rose (HR) [Hindmarsh and Rose (1984)] slow-fast neuron model for each node of the networks.

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Printed December 25, 2017;
Published ahead of print December 27, 2017; Printed December 25, 2017; OM&P 2017 Volume 3 Issue 3, 4, pages 84-92; doi:10.20388/omp2017.003.0049
Abstract Full Text

This review focuses on temperature dependence of biophysical properties of ion channels of other than TRP types. Some functional consequences of the channels temperature sensitivity for neuronal excitation in health and disease are considered.

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Printed December 25, 2017;
Published ahead of print December 18, 2017; Printed December 25, 2017; OM&P 2017 Volume 3 Issue 3, 4, pages 99-107; doi:10.20388/omp2017.003.0052
Abstract Full Text

Neurons of the substantia nigra are most prone to degeneration in Parkinson’s disease. The cause of their vulnerability remains unclear and knowledge of the molecular and microstructural features of the substantia nigra pars compacta will help understanding why nigral neurons are vulnerable to damaging factors. 
The present study was aimed to investigate the intranuclear inclusions of the nigral neurons, the Marinesco bodies and the Roncoroni rodlets, which origin and function are uncertain, using ubiquitin-, tyrosine hydroxylase-, nitric oxide synthase-, calbindin-, NeuN-, glutamic acid decarboxylase-, and  α-tubulin-immunohistochemistry and iron histochemistry with DAB enhancement.
Of the tested substances, tyrosine hydroxylase and nitric oxide synthase were revealed for the first time in the Marinesco bodies. Non-heme iron was found for the first time in both the Marinesco bodies and the Roncoroni rodlets. In accordance with previous studies, ubiquitin-immunoreactivity was demonstrated in the Marinesco bodies. Moreover, we describe some smaller round and dot-like ubiquitin-immunoreactive structures in the nucleus of melanized neurons. The found small ubiquitin-immunopositive structures within the nucleus are proposed to be the developmental stages of growing Marinesco bodies, whereas Marinesco bodies themselves seem to label the neurons with impaired function of proteasome. 

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Printed December 25, 2017;
Published ahead of print December 18, 2017; Printed December 25, 2017; OM&P 2017 Volume 3 Issue 3, 4, pages 71-83; doi:10.20388/omp2017.003.0048
Abstract Full Text

Recurrent epileptiform activity induces network sodium oscillations in the juvenile hippocampus. In CA1 pyramidal neurons, these oscillations are mainly caused by opening of glutamate-gated ion channels, while in astrocytes, sodium increases are due to sodium-dependent glutamate uptake. Astrocytes express the glutamate transporters GLAST and GLT- 1, which exhibit differential expression patterns during postnatal development. The specific contribution of these transporter subtypes to sodium oscillations is not known. We addressed this question by performing somatic sodium imaging in hippocampal tissue slices from neonatal (postnatal days (P) 2-4) and two-week-old (P14-16) mice. We found that perfusion with Mg2+-free, bicuculline-containing saline caused sodium oscillations in both developmental stages. Moreover, at both P2-4 and P14-16, application of TFB-TBOA to inhibit GLAST and GLT-1 generated fast sodium loading of neurons and termination of oscillatory activity, accompanied by loss of membrane integrity of neurons, while astrocytes experienced only minor increases in baseline sodium. DHK, a GLT-1-specific blocker, induced moderate sodium loading of neurons, reduced the amplitude of neuronal sodium oscillations and increased the oscillation frequency in two-week-old mice. In neonatal animals, DHK increased baseline sodium and reduced the peak amplitude of sodium transients as well, but exerted only moderate effects on network activity. Taken together, our experiments demonstrate the essential role of glutamate uptake for sodium homeostasis and neural function already in the early neonatal brain. Moreover, they suggest that, although GLAST dominates in neonatal tissue and GLT-1 is predominant at P14-16, both transporter subtypes functionally contribute to glutamate clearance during the first three weeks after birth. 

 

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Printed December 25, 2017;
Published ahead of print December 18, 2017; Printed December 25, 2017; OM&P 2017 Volume 3 Issue 3, 4, pages 59-70; doi:10.20388/omp2017.003.0051
Abstract Full Text

The aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c., once daily, for 14 days) on the anxiety-like and depression-like behaviors following long-term ovariectomy (12 weeks) in female rats. Cholecalciferol was administered to the ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol after long-term absence of estrogen (17β-E2, 0.5 µg/rat, s.c., once daily, for 14 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM), depression-like behavior was assessed in the forced swimming test (FST), locomotor and grooming activities were assessed in the open field test (OFT). The treatment with cholecalciferol (1.0 mg/kg/day, s.c.) in the OVX rats after long-term absence of estrogens induced antidepressant-like effect (p<0.05). Moreover, cholecalciferol in this dose plus 17β-E2 more markedly exhibited antidepressant-like effect in the OVX rats after long-term ovariectomy (p<0.05). The OVX rats treated with cholecalciferol at doses of 1.0 mg/kg and 2.5 mg/kg demonstrated a decrease of anxiety-like behavior in the EPM. The combination of cholecalciferol at doses of 1.0 and 2.5 mg/kg with a low dose of 17β-E2 more effectively decreases anxiety-like behavior in the OVX rats after long-term estrogen deficiency than17β-E2 alone. This work promotes more effective creation of novel therapeutic targets and strategies for affective-related disorders treatment in female subjects with long-term estrogen deficiency.

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Symposium
Printed September 15, 2017;
Published ahead of print September 13, 2017; Printed September 15, 2017; OM&P 2017 Volume 3 Supplement S 1, pages 1-15; doi:10.20388/omp2017.00s1.001
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Printed September 15, 2017;
Published ahead of print September 13, 2017; Printed September 15, 2017; OM&P 2017 Volume 3 Supplement S 1, pages 16
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