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OM&P
Section CELLULAR NEUROSCIENCE
Acknowledgements
This work was supported by Program "Molecular and Cell Biology" and grant Russian Science Foundation (14-15-00942). References
1. C. Suter-Crazzolara, K.Unsicker, Neuroreport, 1994, 5, 2486-2488.
2. N. Kust, D. Panteleev, I. Mertsalov, et al., Mol Neurobiol., 2015,51(3),1195-1205.
Excitation-Energy Coupling and Vesicle-Based Signaling in Astrocytes
Nina Vardjan, Marko Kreft, Helena H. Chowdhury, Anemari Horvat, Matjaz Stenovec, Eva Lasic, Marjeta Lisjak, Bostjan Rituper, Jernej Jorgacevski, Maja Potokar, Mateja Gabrijel, Robert Zorec*
Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, Celica BIOMEDICAL, Lab Cell Engineering, Ljubljana, Slovenia. * Presenting e-mail: robert.zorec@celicabiomedical.com
Astrocytes, a heterogeneous glial cell type, get excited when neurotransmitters, such as noradrenaline (NA) and ATP bind to their membrane receptors and respond back by releasing their own signals. This involves vesicles, which store chemicals termed gliotransmitters or more generally gliosignaling molecules. In the former case chemical messengers get released from astrocytic sites proximal to the synapse, which defines communication to occur in the micro-space of contact between the synapse and the astrocyte. In contrast gliosignaling molecules may also be released into the extracellular space and get transported to locations far away from the active astrocyte. This mode of release resembles the endocrine system. Hence astrocytes are considered to be part of the gliocrine system in the brain, where the glymphatic system mediates the convection of released molecules. This complex system not only plays a role in cell-to-cell communication but also synchronizes the provision of energy for neural networks. Astrocytes contain glycogen, a form of energy store. Excitation of astrocytes by volume transmitters, such as NA, released by locus coeruleus neurons, activates adrenergic receptors and stimulates glycogenolysis, providing lactate. This lecture will discuss how astrocytes operate to synchronize excitation and energy provision. Moreover, Ca2+ -dependent fusion of the vesicle membrane with the plasma membrane in astrocytes will be presented.
Using an approach to study single astrocytes by quantitative imaging confocal microscopy, we studied how stimuli like noradrenaline or ATP activate cytosolic calcium signals and how the mobility of fluorescently labelled secretory vesicles is affected by physiological states of astrocytes. By fluorescence resonance energy transfer (FRET) nanosensors we also measured second messenger cAMP and metabolites, such as D-glucose and L-lactate. Stimulation of astrocytes by noradrenaline increases cytosolic calcium and cAMP in distinct time-domains. Vesicle mobility was differentially modulated, depending of the vesicle cargo, by elevations in cytosolic calcium levels. NA also stimulated glycolysis monitored as an increase in FRET-based cAMP and cytosolic L-lactate increase, while cytosolic D-glucose levels were decreased due to facilitated consumption in glycolysis.It is proposed that excited astrocytes liberate energy by enhanced glycolysis, while a complex vesicle -ased signalling response is taking place in the same time domain. Hence, excitation-energy coupling is time-associated with alterations in astrocytic vesicle-based communication capacity.
Offline Effects of Single and Paired Pulse TMS
Evgeni Blagovechtchenski*, Tommaso Fedele, Maria Nazarova, Vadim Nikulin
Saint-Petersburg State University, Russia. * Presenting e-mail: zhenja@gmail.com
All effects produced by TMS are mainly two types: online or offline. Online TMS effects (behavior and electrophysiological) described as lasting less than 1 second after stimulation. Offline TMS on the other hand means that the stimulation effects lasting seconds and minutes. Single and paired plus (ppTMS) stimulations are considered as online (Terao et.al.,
12 Opera Med Physiol 2016 Vol. 2 (S1)
Section CELLULAR NEUROSCIENCE
2006). We checked EEG state before and after blocks of random single (110% MT) and paired (90% - 110% MT, 2 or 10 ms IPI (intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI)); 4 - 8 sec between single or paired pulses) pulse stimulation (about 300 total stimuli) by calculation of Long-Range Temporal Correlations (LRTC, Linken-kaer-Hansen et al., 2001; Nikulin et al., 2012) in EEG . LRTC in the alpha frequency range were calculated with Detrend-ed Fluctuation Analysis applied to multichannel EEG recordings.
LRTC in the alpha frequency range showed moderate intra-class correlation between the two rest sessions thus indicating a relative stability of the temporal dynamics between the sessions. Topographically, intra-class correlation was least pronounced over the stimulated areas thus demonstrating a potential long-lasting offline effect of TMS on neuronal activity. This was further confirmed by showing that there was a positive correlation between the magnitude of ICF and the magnitude of LRTC in 8-13 Hz range. Importantly, such correlation was regionally specific demonstrating strongest values over sensorimotor areas where TMS was applied. Our data suggests single and paired pulses TMS can have a previously unobserved long lasting effect on the temporal dynamics of neuronal oscillations and can be considered as offline.
References
1. Terao Y, Ugawa Y(2006),' Studying higher cerebral functions by transcranial magnetic stimulation.' Suppl Clin Neuro-physiol., vol. 59, pp.9-17.
2. Linkenkaer-Hansen, K. (2001), 'Long-range temporal correlations and scaling behavior in human brain oscillations.' Journal of Neuroscience, vol. 21, no. 4, pp. 1370-1377
3. Nikulin, V. (2012), 'Attenuation of long-range temporal correlations in the amplitude dynamics of alpha and beta neuronal oscillations in patients with schizophrenia.' NeuroImage, vol. 61 no. 1, pp. 162-169
OM&P
Role of the Oligodendrocyte Lineage in Acute CNS Trauma
Frank Kirchhoff *
Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, Homburg, Germany. * Presenting e-mail: frank.kirchhoff@uks.eu
Acute brain injuries activate signaling cascades essential for scar formation. Here, we report that acute lesions associated with a disruption of the blood-brain barrier (BBB) trigger re-programming of the oligodendrocyte lineage. Differentiated oligodendrocytes and their precursor cells can generate another neuroglial cell type: astrocytes. By in vivo 2P-LSM analysis we followed oligodendrocytes after injury in PLP-DsRed/GFAP-EGFP transgenic mice. Adjacent to the lesion site, oligodendrocytes first turned into an intermediate cell stage with astro- and oligodendroglial gene expression properties (AO cells). Subsequently, portions of AO cells differentiated into astrocytes, while others stayed in the oligodendrocyte lineage. In split-Cre mice, AO cells showed a clear glia-restricted differentiation potential that also depended on local cues. At the lesion higher expression levels of glial differentiation factors were detected. And indeed, local injection of IL-6 promoted the formation of AO cells. In summary, our findings highlight the plastic potential of oligodendrocytes in acute brain trauma.
Molecular Changes in Penumbra After Focal Photothrombotic Stroke in the Rat Cerebral Cortex
A.B. Uzdensky* and S.V. Demyanenko
Southern Federal University, Rostov-on-Don, Russia. * Presenting e-mail: auzd@yandex.ru
Aims
Ischemic stroke is a leading cause of human disability and mortality. Vascular occlusion and energy deficit rapidly, for a few minutes induce cerebral infarct. The cell damage propagates from the infarct core to surrounding tissues (penumbra). Acute cell necrosis inside the infarct core cannot be prevented, but tissue damage in penumbra develops slower,
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