PMID- 28430606 OWN - NLM STAT- MEDLINE DCOM- 20180416 LR - 20181113 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 20 DP - 2017 May 16 TI - Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway. PG - 32433-32449 LID - 10.18632/oncotarget.15405 [doi] AB - Ketamine has been reported to impair the capacity for learning and memory. This study examined whether these capacities were also altered in the offspring and investigated the role of the CREB signaling pathway in pregnant rats, subjected to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris water maze task, contextual and cued fear conditioning, and olfactory tasks were executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats were sacrificed on B30. Nerve density and dendritic spine density were examined via Nissl's and Golgi staining. Simultaneously, the contents of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII), p-CaMKII, CaMKIV, p-CaMKIV, Extracellular Regulated Protein Kinases (ERK), p-ERK, Protein Kinase A (PKA), p-PKA, cAMP-Response Element Binding Protein (CREB), p-CREB, and Brain Derived Neurotrophic Factor (BDNF) were detected in the hippocampus. We pretreated PC12 cells with both PKA inhibitor (H89) and ERK inhibitor (SCH772984), thus detecting levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. The results revealed that ketamine impaired the learning ability and spatial as well as conditioned memory in the offspring, and significantly decreased the protein levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. We found that ERK and PKA (but not CaMKII or CaMKIV) have the ability to regulate the CREB-BDNF pathway during ketamine-induced anesthesia in pregnant rats. Furthermore, ERK and PKA are mutually compensatory for the regulation of the CREB-BDNF pathway. FAU - Li, Xinran AU - Li X AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Guo, Cen AU - Guo C AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Li, Yanan AU - Li Y AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Li, Lina AU - Li L AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Wang, Yuxin AU - Wang Y AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Zhang, Yiming AU - Zhang Y AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Li, Yue AU - Li Y AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Chen, Yu AU - Chen Y AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Liu, Wenhan AU - Liu W AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. FAU - Gao, Li AU - Gao L AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 690G0D6V8H (Ketamine) SB - IM MH - Animals MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Female MH - Humans MH - Ketamine/*adverse effects MH - Learning/*drug effects MH - Male MH - Memory/*drug effects MH - Pregnancy MH - Rats MH - Rats, Wistar MH - Signal Transduction PMC - PMC5464800 OTO - NOTNLM OT - CREB pathway OT - Neuroscience OT - ketamine OT - learning and memory OT - pregnant rats OT - rat offspring COIS- CONFLICTS OF INTEREST There is no conflict of interest. EDAT- 2017/04/22 06:00 MHDA- 2018/04/17 06:00 PMCR- 2017/05/16 CRDT- 2017/04/22 06:00 PHST- 2016/12/21 00:00 [received] PHST- 2017/01/27 00:00 [accepted] PHST- 2017/04/22 06:00 [pubmed] PHST- 2018/04/17 06:00 [medline] PHST- 2017/04/22 06:00 [entrez] PHST- 2017/05/16 00:00 [pmc-release] AID - 15405 [pii] AID - 10.18632/oncotarget.15405 [doi] PST - ppublish SO - Oncotarget. 2017 May 16;8(20):32433-32449. doi: 10.18632/oncotarget.15405.