Transient disturbances in contextual fear memory induced by Aβ(25–35) in rats are accompanied by cholinergic dysfunction

• Published in: Behavioural brain research Vol. 259; pp. 152 - 157
• Main Authors: Stepanichev, Mikhail, Lazareva, Natalia, Tukhbatova, Gulnur, Salozhin, Sergey, Gulyaeva, Natalia
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.02.2014; Elsevier
• Subjects: Amyloid beta-Peptides - toxicity; Amyloid-β (25–35); Analysis of Variance; Animals; Choline acetyltransferase; Choline O-Acetyltransferase - genetics; Choline O-Acetyltransferase - metabolism; Cholinergic neurons; Cholinergic Neurons - pathology; Cholinergic phenotype; Conditioning (Psychology) - drug effects; Contextual fear conditioning; Fear - drug effects; Gene Expression Regulation - drug effects; Male; Medial septum; Memory Disorders - chemically induced; Peptide Fragments - toxicity; Rats; Rats, Wistar; RNA, Messenger - metabolism; Septal Nuclei - pathology; Time Factors; Vesicular Acetylcholine Transport Proteins - genetics; Vesicular Acetylcholine Transport Proteins - metabolism; Vesicular acetylcholine transporter; Contextual fear conditioning; Cholinergic phenotype; Choline acetyltransferase; Medial septum; Cholinergic neurons; Amyloid-β (25–35); Vesicular acetylcholine transporter
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2013.11.013

•Aβ(25–35) induces transient impairment in contextual fear conditioning.•Aβ(25–35) induces progressive decrease of ChAT expressing neurons in MS.•Aβ(25–35) induces long-term decline in ChAT and VaChT mRNA in MS.•Aβ(25–35) induces loss of septal neurons cholinergic phenotype without cell death. 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.