' 0007-4888/00/0009-921$25.00 © 2000 Kluwer Academic/Plenum Publishers Effects of Ethanol and Acetaldehyde on Isolated Nerve Ending Membranes: Study by Atomic-Forced Microscopy O. V. Chumakova, A. V. Liopo, S. A. Chizhik,* V. V. Tayurskaya, L. L. Gerashchenko, and O. Yu. Komkov* Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 130, No. 9, pp. 356-359, September, 2000 Original article submitted April 12, 2000 A new method of fixation of native synaptosomes and synaptosomal membranes from rat striatum was applied for their visualization by atomic-force microscopy. A scheme for ex- amination of the surface of biological material was developed, which helps to distinguish intact synaptosomes from washed synaptic membranes and evaluate damage to synaptic mem- brane surface caused by ethanol (25 mM) and acetaldehyde (50 µM). The proposed method can be used for evaluation of the damaging effects of ethanol and acetaldehyde on neurons. Key Words: synaptosomes; synaptic membranes; atomic-force microscopy; ethanol; acetaldehyde Institute of Biochemistry, National Academy of Sciences of Belarus, Grodno; *V. A. Balyi Institute of Mechanics of Metal Polymeric Systems, National Academy of Sciences of Belarus, Gomel’. Address for corre- Address for corre- Address for corre- Address for corre- Address for corre- spondence: spondence: spondence: spondence: spondence: val@biochem.unibel.by. Chumakova O.V. Neuronal surface and synaptic contacts, are an impor- tant characteristics determining the function of ner- vous tissue. Isolated nerve endings (synaptosomes) are often used as the model system for investigation of neuronal membranes. As a substrate of signal processes, neuronal membrane is very sensitive to effectors and bio- active compounds [1]. Ethanol (ET) and acetaldehyde (AA) induce specific changes in synaptic structures of the brain, which probably underlie alcohol tolerance [13]. Identification of ET and AA effects on the membrane is a pressing problem [2], because the level of ET and its metabolites in tissues is important for evaluation of the severity of alcoholization and neuron damage. The aim of this study was to elaborate a method for visualization of synaptosomes and neuronal mem- branes by atomic-force microscopy (AFM) and detec- tion of possible damaging effects of AA and ET on neuronal membranes. MATERIALS AND METHODS Synaptosome-rich fraction isolated from rat striatum as described previously [6] was resuspended in normal KrebsRinger solution (pH 7.4) and left for 30 min for recovery of the synaptosome ultrastructure. The suspension (4 µl) containing 300-500 µg protein per 0.1 ml was transferred to slide and fixed by heating. For obtaining synaptic membranes, dense synap- tosome precipitate was frozen and after thawing washed twice with 20 mM sodium phosphate buffer (pH 7.4), the precipitate was resuspended in normal KrebsRinger solution (pH 7.4), 4 µl suspension was transferred to slide and fixed. Synaptic membranes were incubated with ET and AA in final concentrations of 25 mM and 50 µM, re- spectively, for 20 min. Similar concentrations were detected in rat blood 0.5 h after injection of ET in a dose of 1.5 g/kg [8]. The level of AA is usually 0.1- 0.2% of tissue ET concentration. The surface of synaptosomes and synaptic mem- branes was examined under a Nanotope-203 comput- er-assisted atomic-force microscope in a tapping-mode regimen, which represented a combination of contact and contact-free examination. The images obtained after a shock wave reflect topographic and elastic properties of the surface [11,12]. During scanning the phase of the probe oscillations changes yielding the so-called phase images. Phase image is a density map, the maximum alteration of oscillation phase characterizes the maximum changes in elastic properties of the material [3]. Bulletin of Experimental Biology and Medicine, No. 9, 2000 METHODS