Endoplasmic reticulum stress induces spatial memory deficits by activating GSK-3.
Li LinJie CaoShu-Sheng YangZheng-Qi FuPeng ZengJiang ChuLin-Na NingTeng ZhangYan ShiQing TianXin-Wen ZhouJian-Zhi WangPublished in: Journal of cellular and molecular medicine (2018)
Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague-Dawley (SD) rats to induce the unfolded protein response (UPR), demonstrated by the enhanced phosphorylation of pancreatic ER kinase (PERK), inositol-requiring enzyme-1 (IRE-1) and activating transcription factor-6 (ATF-6). We observed that UPR induced spatial memory deficits and impairments of synaptic plasticity in the rats. After TM treatment, GSK-3β was activated and phosphorylation of cAMP response element binding protein at Ser129 (pS129-CREB) was increased with an increased nuclear co-localization of pY126-GSK-3β and pS129-CREB. Simultaneous inhibition of GSK-3β by hippocampal infusion of SB216763 (SB) attenuated TM-induced UPR and spatial memory impairment with restoration of pS129-CREB and synaptic plasticity. We concluded that UPR induces AD-like spatial memory deficits with mechanisms involving GSK-3β/pS129-CREB pathway.
Keyphrases
- endoplasmic reticulum stress
- signaling pathway
- endoplasmic reticulum
- pi k akt
- induced apoptosis
- binding protein
- working memory
- transcription factor
- traumatic brain injury
- protein kinase
- high glucose
- diabetic rats
- low dose
- small molecule
- drug induced
- multiple sclerosis
- pulmonary hypertension
- resting state
- cell proliferation
- cerebral ischemia
- cognitive decline
- heart failure
- left ventricular
- subarachnoid hemorrhage
- tyrosine kinase
- temporal lobe epilepsy
- estrogen receptor
- stress induced
- combination therapy
- brain injury