title: Transient disturbances in contextual fear memory induced by Aβ(25-35) in rats are accompanied by cholinergic dysfunction.
abstract: Damage to the medial septum (MS) or disruption of the septo-hippocampal pathway is often considered as a basis for memory impairments, manifesting in the hippocampus-dependent behavioral paradigms. In the present study, we have examined the effects of intracerebroventricular administration of aggregated amyloid-β (25-35) (Aβ(25-35)) on contextual fear conditioning and the condition of cholinergic neurons in the MS using immunohistochemical detection of choline acetyltransferase (ChAT) and expression of the "cholinergic locus genes" (ChAT and vesicular acetylcholine transporter (VaChT) mRNA). A single injection of Aβ(25-35) induced transient moderate impairments in contextual fear conditioning accompaniedby a decrease in ChAT expression. However, the long-term decline in ChAT and VaChT expression was not associated with stable impairments in contextual fear memory. An Aβ(25-35)-induced progressive decrease in the number of ChAT expressing neurons in the MS was revealed, but no gross neuronal cell loss in the MS could be detected (as judged by the density of NeuN-immunoreactive cells). Thus, Aβ(25-35) induced a loss of the cholinergic phenotype of septal neurons without neuronal cell death in MS. The data give an additional support to the concept of early impairments in the synthesis of proteins related to the cholinergic system as an important mechanism in amyloid-induced neuronal damage.
authors.affiliation: Laboratory of Functional Biochemistry of Nervous System, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Stepanichev
authors.affiliation: Laboratory of Functional Biochemistry of Nervous System, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lazareva
authors.affiliation: Laboratory of Molecular Neurobiology Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Gulnur
authors.initials: G
authors.lastname: Tukhbatova
authors.affiliation: Laboratory of Molecular Neurobiology Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Salozhin
authors.affiliation: Laboratory of Functional Biochemistry of Nervous System, Russian Academy of Sciences, Moscow, Russia. Electronic address: nata_gul@pisem.net.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gulyaeva
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D059329:Cholinergic Neurons / Q000473:pathology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D010446:Peptide Fragments / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000473:pathology*; D013997:Time Factors; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D050494:Vesicular Acetylcholine Transport Proteins; C074636:amyloid beta-protein (25-35); D002795:Choline O-Acetyltransferase
keywords: Amyloid-β (25–35); Choline acetyltransferase; Cholinergic neurons; Cholinergic phenotype; Contextual fear conditioning; Medial septum; Vesicular acetylcholine transporter