caa a22 4500 606235825 CHVBK 20210128101244.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s11010-015-2561-5 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2561-5 Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington's disease [Elektronische Daten] [Arpit Mehrotra, Abhilasha Sood, Rajat Sandhir] 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-l-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondriaisolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animalshad impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA+ALCAR for 21days normalized mitochondrial lipid composition, improvedmitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD. Springer Science+Business Media New York, 2015 3-Nitropropionic acid nationallicence Huntington's disease nationallicence Alpha-lipoic acid nationallicence Acetyl- l -carnitine nationallicence Mitochondria nationallicence Lipid composition nationallicence ALA : Alpha-lipoic acid nationallicence ALCAR : Acetyl-l-carnitine nationallicence 3-NP : 3-Nitropropionic acid nationallicence HD : Huntington's disease nationallicence PC : Phosphatidylcholine nationallicence PE : Phosphatidylethanolamine nationallicence PS : Phosphatidylserine nationallicence CL : Cardiolipin nationallicence Mehrotra Arpit Department of Biochemistry, Panjab University, 160014, Chandigarh, India aut Sood Abhilasha Department of Biochemistry, Panjab University, 160014, Chandigarh, India aut Sandhir Rajat Department of Biochemistry, Panjab University, 160014, Chandigarh, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 281-292 0300-8177 410:1-2<281 2015 410 11010 https://doi.org/10.1007/s11010-015-2561-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2561-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mehrotra Arpit Department of Biochemistry, Panjab University, 160014, Chandigarh, India aut NATIONALLICENCE 700 1- Sood Abhilasha Department of Biochemistry, Panjab University, 160014, Chandigarh, India aut NATIONALLICENCE 700 1- Sandhir Rajat Department of Biochemistry, Panjab University, 160014, Chandigarh, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 281-292 0300-8177 410:1-2<281 2015 410 11010