Behavioral alterations associated with a down regulation of HCN1 mRNA in hippocampal cornus ammon 1 region and neocortex after chronic incomplete global cerebral ischemia in rats.
It has been suggested that hyperpolarization-activated cyclic-nucleotide-gated cation non-selective channel (HCN) 1 is primarily expressed in the hippocampus and can be regulated in many pathological settings. However, little is known about its change under ischemic conditions. In the present study, we performed neurophysiological recordings of sham-operated and chronic ischemic rats with hypoperfusion during the resolution of the neurological deficits respectively. In situ hybridization methods and reverse transcriptase-polymerase chain reaction (RT-PCR) assays were used to investigate whether and how HCN1 mRNA may be altered in global incomplete chronic cerebral ischemic rat model. Our results suggested that attenuated spatial learning and memory function of rats shown by longer escape latency, shorter time spent in the target quadrant and impaired long-term potentiation (LTP) after chronic cerebral ischemia. In the in situ hybridization cytochemistry experiment, HCN1 mRNA declined to 52.00% and 46.00% of the control values in the cornus ammon 1 (CA1) regions of hippocampus and neocortex separately after chronic cerebral ischemia. HCN1 mRNA in the hippocampal CA1 region and neocortex was markedly down regulated by ischemia, reaching 48.90% and 45.80% of the control values respectively in the semi-quantitative RT-PCR experiment. The phenomenon opened new insights for further investigation of the physiological and pathological significances of HCN1 in chronic incomplete global cerebral ischemia.
Li
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S
Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, PR China.
He
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Z
Guo
L
L
Huang
L
L
Wang
J
J
He
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W
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D056547:CA1 Region, Hippocampal / Q000503:physiopathology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007859:Learning Disabilities / Q000209:etiology / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D019579:Neocortex / Q000503:physiopathology*; D015221:Potassium Channels / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000502:physiology; D013997:Time Factors
D054815:Cyclic Nucleotide-Gated Cation Channels; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D012333:RNA, Messenger