title: Tremella fuciformis enhances the neurite outgrowth of PC12 cells and restores trimethyltin-induced impairment of memory in rats via activation of CREB transcription and cholinergic systems.
abstract: The present study examined the effects of Tremella fuciformis (TF) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered saline or TF (TF 25, 50, 100 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of TF on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing Choline acetyltransferase (ChAT) and cAMP responsive element binding protein (CREB) immunohistochemistry. In order to confirm the underlying mechanisms of the memory enhancing effects of TF, we assessed the neurite outgrowth of PC12 cells. We also administered 18F-fluorodeoxyglucose and performed a PET scan of the frontal lobe. The rats with TMT injection showed impaired learning and memory of the tasks and treatment with TF produced a significant improvement of the escape latency to find the platform in the Morris water maze compared to that of the control group. In the retention test, the TF50 group showed increased time spent around the platform compared to that of the control group. Consistent with the behavioral data, TF50 mg/kg significantly alleviated the loss of ChAT-ir neurons in the hippocampus compared to that of the control group. Treatment with TF significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the control group. In addition, TF treatment (50 mg/kg) increased the glucose uptake approximately sevenfold in the frontal lobe and it significantly promoted neurite outgrowth of the PC12 cells, as compared to that of the controls. These results suggest that TF may be useful for improving the cognitive function via regulation of the CREB signaling pathway and cholinergic system in the hippocampus.
authors.affiliation: Department of Integrative Medicine and the Research Center of Behavioral Medicine, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Shim
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Ahn
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Kum Ju
authors.initials: KJ
authors.lastname: Park
authors.forename: Woong Ki
authors.initials: WK
authors.lastname: Choi
authors.forename: Hyo-Cheol
authors.initials: HC
authors.lastname: Ha
authors.forename: Jung Il
authors.initials: JI
authors.lastname: Kang
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Kim
authors.forename: Ik Hyun
authors.initials: IH
authors.lastname: Yeo
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Insop
authors.initials: I
authors.lastname: Shim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019788:Fluorodeoxyglucose F18; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016501:Neurites / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016716:PC12 Cells / Q000166:cytology; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000633:toxicity
chemical_list: D018678:Cholinergic Agents; D018696:Neuroprotective Agents; D011134:Polysaccharides; D014298:Trimethyltin Compounds; C502294:tremellan; D019788:Fluorodeoxyglucose F18; C046488:trimethyltin; D050882:CREB-Binding Protein; D002795:Choline O-Acetyltransferase