High ω3-polyunsaturated fatty acids in fat-1 mice prevent streptozotocin-induced Purkinje cell degeneration through BDNF-mediated autophagy.
Loss of Purkinje cells has been implicated in the development of diabetic neuropathy, and this degeneration is characterized by impairment of autophagic processes. We evaluated whether fat-1 transgenic mice, a well-established animal model that endogenously synthesizes ω3 polyunsaturated fatty acids (ω3-PUFA), are protected from Purkinje cell degeneration in streptozotocin (STZ)-treated model with fat-1 mice. STZ-treated fat-1 mice did not develop hyperglycemia, motor deficits, or Purkinje cell loss. The expression of LC3 I, II, Beclin-1 and p62 were increased in the cerebellum of STZ-treated wild-type mice, and these expressions were more increased in STZ-treated fat-1 mice, but not of p62. Moreover, cerebellar Rab7, Cathepsin D, and ATP6E were increased in STZ-treated fat-1 mice. There was also increased BDNF expression in Purkinje cells without any changes in TrkB, and phosphorylation of Akt and CREB in the cerebellums of fat-1 mice. Collectively, these findings indicate that STZ-treated fat-1 mice were protected from Purkinje cell loss and exhibited increased BDNF signaling, enhancing autophagic flux activity in cerebellar Purkinje neurons. These processes may underlie Purkinje cell survival and may be potential therapeutic targets for treatment of motor deficits related to diabetic neuropathy.
Department of Anatomy, College of Medicine, Konyang University of Korea, Daejeon, South Korea.
Dong Ho
DH
Bak
Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, South Korea.|Department of Anesthesiology, Yanbian University Hospital, Yanbian, 133000, China.
Enji
E
Zhang
Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, South Korea.
Min-Hee
MH
Yi
Department of Pharmacology, College of Medicine, Konyang University of Korea, Daejeon, South Korea.
Do-Kyung
DK
Kim
Department of Biochemistry, Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, South Korea.
Kyu
K
Lim
Department of Anatomy, College of Medicine, Konyang University of Korea, Daejeon, South Korea.
Jwa-Jin
JJ
Kim
Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, South Korea.
Dong Woon
DW
Kim
D000818:Animals; D001343:Autophagy; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D011689:Purkinje Cells / Q000187:drug effects* / Q000473:pathology; D013311:Streptozocin / Q000633:toxicity*
D019208:Brain-Derived Neurotrophic Factor; D015525:Fatty Acids, Omega-3; D013311:Streptozocin