PMID- 29200900
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1226-4512 (Print)
IS  - 2093-3827 (Electronic)
IS  - 1226-4512 (Linking)
VI  - 21
IP  - 6
DP  - 2017 Nov
TI  - Genistein attenuates isoflurane-induced neurotoxicity and improves impaired 
      spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt 
      signaling.
PG  - 579-589
LID - 10.4196/kjpp.2017.21.6.579 [doi]
AB  - Anesthetics are used extensively in surgeries and related procedures to prevent 
      pain. However, there is some concern regarding neuronal degeneration and 
      cognitive deficits arising from regular anesthetic exposure. Recent studies have 
      indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response 
      element-binding protein (CREB) are involved in learning and memory processes. 
      Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective 
      effects. The present study was performed to examine the protective effect of 
      genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were 
      exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups 
      of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg 
      body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. 
      Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining 
      following isoflurane exposure. Genistein significantly reduced apoptosis in the 
      hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and 
      cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR 
      analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively 
      upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to 
      activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also 
      significantly activated. Genistein administration improved general behavior and 
      enhanced learning and memory in the rats. These observations suggest that 
      genistein exerts neuroprotective effects by suppressing isoflurane-induced 
      neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.
FAU - Jiang, Tao
AU  - Jiang T
AD  - Department of Anesthesiology, Shandong Cancer Hospital, Jinan 250117, Shandong 
      Province, China.
FAU - Wang, Xiu-Qin
AU  - Wang XQ
AD  - Department of Anesthesiology, Shandong Cancer Hospital, Jinan 250117, Shandong 
      Province, China.
FAU - Ding, Chuan
AU  - Ding C
AD  - Department of Anesthesiology, Shandong Cancer Hospital, Jinan 250117, Shandong 
      Province, China.
FAU - Du, Xue-Lian
AU  - Du XL
AD  - Department of Gynecology, Shandong Cancer Hospital, Jinan 250117, Shandong 
      Province, China.
LA  - eng
PT  - Journal Article
DEP - 20171030
PL  - Korea (South)
TA  - Korean J Physiol Pharmacol
JT  - The Korean journal of physiology & pharmacology : official journal of the Korean 
      Physiological Society and the Korean Society of Pharmacology
JID - 9709505
PMC - PMC5709474
OTO - NOTNLM
OT  - BDNF
OT  - CREB
OT  - Genistein
OT  - Isoflurane
OT  - Neurodegeneration
OT  - Phosphatidylinositol 3-kinase
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest.
EDAT- 2017/12/05 06:00
MHDA- 2017/12/05 06:01
PMCR- 2017/11/01
CRDT- 2017/12/05 06:00
PHST- 2016/06/06 00:00 [received]
PHST- 2016/08/02 00:00 [revised]
PHST- 2016/08/18 00:00 [accepted]
PHST- 2017/12/05 06:00 [entrez]
PHST- 2017/12/05 06:00 [pubmed]
PHST- 2017/12/05 06:01 [medline]
PHST- 2017/11/01 00:00 [pmc-release]
AID - 10.4196/kjpp.2017.21.6.579 [doi]
PST - ppublish
SO  - Korean J Physiol Pharmacol. 2017 Nov;21(6):579-589. doi: 
      10.4196/kjpp.2017.21.6.579. Epub 2017 Oct 30.