Diabetes alters myelin lipid profile in rat cerebral cortex: Protective effects of dihydroprogesterone.
Due to the emerging association of diabetes with several psychiatric and neurodegenerative events, the evaluation of the effects of this pathology on the brain function has now a high priority in biomedical research. In particular, the effects of diabetes on myelin compartment have been poorly taken into consideration. To this purpose, we performed a deep lipidomic analysis of cortical myelin in the streptozotocin-induced diabetic rat model. In male rats three months of diabetes induced an extensive alterations in levels of phosphatidylcholines and phosphatidylethanolamines (the main species present in myelin membranes), plasmalogens as well as phosphatidylinositols and phosphatidylserines. In addition, the levels of cholesterol and myelin basic protein were also decreased. Because these lipids exert important functional and structural roles in the myelin compartment, our data indicate that cerebral cortex myelin is severely compromised in diabetic status. Treatment for one-month with a metabolite of progesterone, dihydroprogesterone, restored the lipid and protein myelin profiles to the levels observed in non-diabetic animals. These data suggest the potential of therapeutic efficacy of DHP to restore myelin in the diabetic brain.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
Gaia
G
Cermenati
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
Silvia
S
Giatti
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
Matteo
M
Audano
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
Marzia
M
Pesaresi
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
Roberto
R
Spezzano
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
Donatella
D
Caruso
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. Electronic address: nico.mitro@unimi.it.
Nico
N
Mitro
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. Electronic address: roberto.melcangi@unimi.it.
Roberto Cosimo
RC
Melcangi
D004092:20-alpha-Dihydroprogesterone / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry; D002853:Chromatography, Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling; D008055:Lipids / Q000737:chemistry*; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D008055:Lipids; D004676:Myelin Basic Protein; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D002784:Cholesterol
Cholesterol; Myelin basic protein; Neuroactive steroids; Phosphatidylcholines; Phosphatidylethanolamines; Plasmalogens