Adiponectin protects rat hippocampal neurons against excitotoxicity.
Adiponectin exerts multiple regulatory functions in the body and in the hypothalamus primarily through activation of its two receptors, adiponectin receptor1 and adiponectin receptor 2. Recent studies have shown that adiponectin receptors are widely expressed in other areas of the brain including the hippocampus. However, the functions of adiponectin in brain regions other than the hypothalamus are not clear. Here, we report that adiponectin can protect cultured hippocampal neurons against kainic acid-induced (KA) cytotoxicity. Adiponectin reduced the level of reactive oxygen species, attenuated apoptotic cell death, and also suppressed activation of caspase-3 induced by KA. Pretreatment of hippocampal primary neurons with an AMPK inhibitor, compound C, abolished adiponectin-induced neuronal protection. The AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, attenuated KA-induced caspase-3 activity. These findings suggest that the AMPK pathway is critically involved in adiponectin-induced neuroprotection and may mediate the antioxidative and anti-apoptotic properties of adiponectin.
Qiu
Guang
G
Department of Neurology, Nanfang Hospital, Nanfang Medical University, Guangzhou, China.
Wan
Ruiqian
R
Hu
Jingping
J
Mattson
Mark P
MP
Spangler
Edward
E
Liu
Shan
S
Yau
Suk-Yu
SY
Lee
Tatia M C
TM
Gleichmann
Marc
M
Ingram
Donald K
DK
So
Kwok-Fai
KF
Zou
Sige
S
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D052242:Adiponectin / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D052242:Adiponectin; D018696:Neuroprotective Agents; D011720:Pyrazoles; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D054419:Receptors, Adiponectin; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; C516138:dorsomorphin; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3; D007608:Kainic Acid