Back to Search
Start Over
Tanshinone IIA ameliorates cognitive deficits by inhibiting endoplasmic reticulum stress-induced apoptosis in APP/PS1 transgenic mice
- Source :
- Neurochemistry international. 133
- Publication Year :
- 2019
-
Abstract
- Our previous data indicated that tanshinone IIA (tan IIA) improves learning and memory in a mouse model of Alzheimer's disease (AD) induced by streptozotocin via restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. This study aims to estimate whether tan IIA inhibits endoplasmic reticulum (ER) stress-induced apoptosis to prevent cognitive decline in APP/PS1 transgenic mice. Tan IIA (10 mg/kg and 30 mg/kg) was intraperitoneally administered to the six-month-old APP/PS1 mice for 30 consecutive days. β-amyloid (Aβ) plaques were measured by immunohistochemisty and Thioflavin S staining, apoptotic cells were observed by TUNEL, ER stress markers and apoptosis signaling proteins were investigated by western blotting and RT-PCR. Our results showed that tan IIA significantly ameliorates cognitive deficits and improves spatial learning ability of APP/PS1 mice in the nest-building test, novel object recognition test and Morris water maze test. Furthermore, tan IIA significantly reduced the deposition of Aβ plaques and neuronal apoptosis, and markedly prevented abnormal expression of glucose regulated protein 78 (GRP78), initiation factor 2α (eIF2α), inositol-requiring enzyme 1α (IRE1α), activating transcription factor 6 (ATF6), as well as suppressed the activation of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) pathways in the parietal cortex and hippocampus. Moreover, tan IIA induced an up-regulation of the Bcl-2/Bax ratio and down-regulation of caspase-3 protein activity. Taken together, the above findings indicated that tan IIA improves learning and memory through attenuating Aβ plaques deposition and inhibiting ER stress-induced apoptosis. These results suggested that tan IIA might become a promising therapeutic candidate drug against AD.
- Subjects :
- Male
medicine.medical_specialty
Glucose-regulated protein
p38 mitogen-activated protein kinases
Morris water navigation task
Apoptosis
Mice, Transgenic
Protein Serine-Threonine Kinases
Hippocampus
Cellular and Molecular Neuroscience
Amyloid beta-Protein Precursor
Cognition
Internal medicine
Endoribonucleases
medicine
Animals
Cognitive decline
Endoplasmic Reticulum Chaperone BiP
biology
Chemistry
ATF6
Endoplasmic reticulum
Cell Biology
Endoplasmic Reticulum Stress
Endocrinology
Abietanes
Unfolded protein response
biology.protein
Female
Cognition Disorders
Subjects
Details
- ISSN :
- 18729754
- Volume :
- 133
- Database :
- OpenAIRE
- Journal :
- Neurochemistry international
- Accession number :
- edsair.doi.dedup.....3baf2f7babc587089073273b307459d7