Opera Medica et Physiologica

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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
Abstract Full Text
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author index.pdf137 KB

Printed June 30, 2017;
Published ahead of print July 16, 2017; Printed June 30, 2017; OM&P 2017 Volume 3 Issue 2, pages 48-58; doi:10.20388/omp2017.002.0045
Abstract Full Text

The rapid advance of super-resolution microscopy and its experimental applications has provided neuroscientists with a pass to the nanoscopic world of synaptic machinery. Here we will briefly overview and discuss current progress in our understanding of the three-dimensional synaptic architecture and molecular organisation as gleaned from the imaging methods that go beyond the diffraction limit of conventional light microscopy. We will argue that such methods are to take our knowledge of synapses to a qualitatively new level, providing the neuroscience research community with novel organising principles and concepts pertinent to the workings of the brain. 

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Printed June 30, 2017;
Published ahead of print June 19, 2017; Printed June 30, 2017; OM&P 2017 Volume 3 Issue 2, pages 39-47; doi:10.20388/omp2017.002.0047
Abstract Full Text

The aim of the present study was to explore the effects of 8-OH-DPAT, 5-HT1A receptor agonist and NAN-190, 5-HT1A receptor antagonist on anxiety-related behavior in the adult gonadectomized (GDX) male rats. Moreover, another goal of this work was to investigate whether the combination of 8-OH-DPAT or NAN-190 plus testosterone propionate (TP) could affect anxiety-like behavior more than TP alone in the adult GDX rats. Two weeks after gonadectomy, GDX rats were subjected by treatments with the solvent, TP (0.5 mg/kg, s.c.), 8-OH-DPAT (0.05 mg/kg, s.c.), NAN-190 (0.1 mg/kg, i.p.), 8-OH-DPAT in a combination with TP or NAN-190 in a combination with TP during 14 days. Experimental groups of GDX rats and control group of intact males were then tested in the elevated plus maze (EPM) and the open field test. 8-OH-DPAT treatment failed to modify anxiety-like behavior of GDX rats in the EPM as compared to the GDX rats given with oil solvent. NAN-190 injected alone or in combination with TP to GDX rats resulted in a significant anxiolytic-like effect as compared to the GDX given with oil solvent or TP application. Our data indicate that the combination of NAN-190 and TP is more effective than TP alone in GDX rats inducing a more profound anxiolytic-like effect in the EPM. Thus, the results of this study suggest that effects of 5-HT1A receptor agonist/antagonist can modify anxiety level in opposite direction in male rats after gonadectomy.

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OMP_2017_02_0047.pdf400.38 KB

Printed June 30, 2017;
Published ahead of print June 18, 2017; Printed June 30, 2017; OM&P 2017 Volume 3 Issue 2, pages 31-38; doi:10.20388/omp2017.002.0046
Abstract Full Text

Nitric oxide (NO) signalling contributes to many biological processes involved in activity-dependent fine tuning of neuronal communication. NO is involved in early developmental signalling of the nervous system and is associated with pathological pathways and age-related decline in neuronal function, thus playing a critical role in regulating neuronal function in physiology and disease. Here we assessed the effects of modulating endogenous neuronal nitric oxide synthase (NOS) activity on synaptic function, specifically on neurotransmitter release at the glutamatergic Drosophila neuromuscular junction (NMJ). We found that the absence of NOS activity enhanced synaptic release at the NMJ and conversely, overexpression of NOS diminished transmitter release. The effects of alterations in NO signalling are the consequence of acute signalling at the synapse as we did not observe any developmental changes in NMJ morphology or synaptic parameters, such as expression of the active zone protein, bruchpilot, which could account for changes in release. Ultrastructural analysis did not show any developmental effects in boutons from larvae with reduced NOS activity. Together, our data present evidence for a negative regulation of transmitter release by NO which has implications for physiological synaptic function but also pathological and age-related dysregulation of synaptic signalling. 

 

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OMP_2017_02_0046.pdf3.06 MB

Printed March 31, 2017;
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 1-13; doi:10.20388/omp2017.001.0041
Abstract Full Text

The role of chaos in biological information processing has been established as an  important breakthrough of nonlinear dynamics, after the early pioneering work of J.S. Nicolis and notably in neuroscience by the work of Walter J. Freeman and co-workers spanning more than three decades.  In this work we revisit the subject and we further focus on novel results that reveal its underlying logical  structure when  faced with the cognition of ambiguous stimuli. We demonstrate, by utilizing a minimal model for apprehension and judgement related to Bayesian updating,  that the fundamental characteristics of a biological processor obey in this case an extended, non-Boolean, logic which is characterized as  a quantum logic. And we realize that in its essence the role of chaos in biological information processing accounts for, and is fully compatible with, the logic of “quantum cognition” in psychology and neuroscience.

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OMP_2017_01_0041.pdf1.37 MB

Printed March 31, 2017;
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 19-24; doi:10.20388/omp2017.001.0042
Abstract Full Text

Understanding the molecular and cellular processes that cause dementia is one of the most important challenges in neuroscience. SUMOylation is a post-translational protein modification that has been strongly implicated in neurodegenerative diseases. To investigate SUMOylation in dementia we profiled the expression of key SUMOylation pathway proteins in post mortem brain tissue from Alzheimer’s Disease (AD) and Down’s Syndrome (DS) patients. As expected, both AD and DS tissue displayed massively increased levels of phosphorylated tau compared to age- and sex-matched controls. Surprisingly, there were no changes in the levels of the E1 and E2 enzymes required for protein SUMOylation, or in levels of the deSUMOylating enzyme SENP1.  There was, however, a marked decrease in the SUMO-2/3-specific deSUMOylating enzyme SENP3 in DS. There were also increased levels of SUMO-1 conjugated proteins in DS, but not in AD tissue. While these results do not exclude roles for SUMOylation in AD, they demonstrate clear differences in the profile of SUMOylation and in the expression of deSUMOylating enzymes between AD and DS brain.

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Printed March 31, 2017;
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 25-29; doi:10.20388/omp2017.001.0044
Abstract Full Text

Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal system, affecting adults and children. Its cause is unknown, and the knowledge of reliable biomarkers is limited, especially for children. That makes the search for new biomarkers and pushing forth the analysis of the available data particularly challenging. We investigate proteomic data from children patients as a promising source, and tackle the problem implementing the recently developed parenclitic network approach to machine learning algorithms that solve classification task for proteomic data from healthy and diseased. We expect our approach to be applicable to other gastrointestinal diseases.

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