It is shown that cognitive defect in case of some neurodegenerative disease is correlated with synapse elimination but not with neuronal loss. Several factors suggests that synapses can be ‘’weak link’ in case of several environmental and metabolic stresses. There are big ratio surface/volume, ‘’second-hand’ mitochondria, calcium influx due neurotransmitter receptors activation. However few data is available on adaptation of synapses to environmental stresses.
We use in our investigation isolated neuronal presynaptic endings termed synaptosomes. Synaptosomes can be prepared from whole brain or different parts of brain from adult animals by homogenization with following differential centrifugation. Synaptosomes remain main properties of intact neuronal presynaptic endings. They able to neurotransmitter release and synaptic vesicle recycling. We use set of fluorescent dyes which permit us to image synaptic vesicle recycling, mitochondria and plasma membrane potential, intracellular sodium and chlorine concentration, free radical formation.
Brain ischemia leads to decrease of extracellular and intracellular pH down to 5.5. We compare influence of extracellular acidification and intracellular acidification induced by amiloride on main function of synaptosomes. It was shown that both decrease pHo and pHi leads to plasma membrane depolarization. Lowering of pHo but not pHi induces oxidative stress in synaptosomes. Further, it was shown that primary source for free radical in this case is intrasynaptosomal mitochondria. Oxidative stress in presynaptic terminals in vivo in case of extracellular acidification can be reason for irreversible synaptic failure in stroke.
Ketogenic diet is used for treatment of epilepsy and Alzheimer disease on early stages. Principle of this method consist in replacing of carbohydrates by fats in everyday food. It leads to increase of ketone bodies level (for instance, beta-hydroxybutirate) in blood. Despite clinical using molecular mechanisms of ketogenic diet are still not clear. We have shown that beta-hydroxybutirate able to fuel synaptic vesicle recycling. However replacing of glucose on beta-hydroxybutirate can inhibits endocytosis. We suggest that inhibiting of endocytosis can partially explain antiseizures properties of ketogenic diet.
Wednesday 4 November 2015, 17:00 - 18:00 h (please note that the time differs from usual)
Building Carré - room CR 3.718