title: Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology.
abstract: Amyloid beta (Aβ) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD) by changing the neuronal excitability. However, the cellular mechanisms by which accumulation of Aβ affects intrinsic neuronal properties are not well understood. The effect of bilateral intra-frontal cortex Aβ (1-42) peptide injection on the intrinsic excitability of hippocampal CA1 pyramidal neurons with particular focus on the contribution of hyperpolarization-activated (Ih) channel currents was examined using whole-cell patch-clamp recording. Passive avoidance memory impairment and morphological changes in rats receiving intra-frontal Aβ treatment were observed, which was associated with significant changes both in passive and active intrinsic electrical membrane properties of CA1 pyramidal neurons. Electrophysiological recording showed a significant decrease in neuronal excitability associated with an augmentation in the first spike after-hyperpolarization (AHP) amplitude. In addition, the depolarizing sag voltage was altered in neurons recorded from Aβ-treated group. In voltage-clamp condition, a hyperpolarizing activated inward current sensitive to ZD7288 and capsaicin was significantly increased in neurons from Aβ-treated rats. The Ih current density was increased and the activation curve was shifted toward less negative potential in the Aβ-treated group as compared to control group. The enhancing effect of Aβ treatment on Ih current was confirmed by showing upregulation of the mRNA of HCN1 channel in the CA1 pyramidal layer of hippocampi. These findings suggest the contribution of Ih and possibly TRPV1 channel currents to the changes induced by Aβ treatment in the intrinsic membrane properties, which, in turn, may provide therapeutic targets for treatment of AD.
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran; Neuroscience Research Center and Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran; Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: M J
authors.initials: MJ
authors.lastname: Eslamizade
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran; Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Saffarzadeh
authors.affiliation: Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
authors.forename: S M M
authors.initials: SM
authors.lastname: Mousavi
authors.affiliation: Neuroscience Research Center and Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran; Neuroscience Research Center, Baqiyatallah (a.s.) University of Medical Sciences, Tehran, Iran.
authors.forename: G H
authors.initials: GH
authors.lastname: Meftahi
authors.affiliation: Neuroscience Research Center and Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Hosseinmardi
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran; Cellular and Molecular Research Center, Faculty of Advanced Technology in Medicine, Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Mehdizadeh
authors.affiliation: Neuroscience Research Center and Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran. Electronic address: Janahmadi@sbmu.ac.ir.
authors.forename: M
authors.initials: M
authors.lastname: Janahmadi
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000150:complications / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000819:agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors
chemical_list: D016229:Amyloid beta-Peptides; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D011743:Pyrimidines; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C082246:ICI D2788; C071423:capsazepine; D002211:Capsaicin
keywords: CA1 pyramidal neurons; Ih channel current; amyloid β (Aβ); intrinsic excitability