Transient disturbances in contextual fear memory induced by Aβ(25-35) in rats are accompanied by cholinergic dysfunction.
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.
['Stepanichev|Mikhail|M|', 'Lazareva|Natalia|N|', 'Tukhbatova|Gulnur|G|', 'Salozhin|Sergey|S|', 'Gulyaeva|Natalia|N|']
D016229:Amyloid beta-Peptides D000704:Analysis of Variance D000818:Animals D002795:Choline O-Acetyltransferase D059329:Cholinergic Neurons D003213:Conditioning, Psychological D005239:Fear D005786:Gene Expression Regulation D008297:Male D008569:Memory Disorders D010446:Peptide Fragments D012333:RNA, Messenger D051381:Rats D017208:Rats, Wistar D012686:Septal Nuclei D013997:Time Factors D050494:Vesicular Acetylcholine Transport Proteins
Medial septum Contextual fear conditioning Cholinergic neurons Choline acetyltransferase Vesicular acetylcholine transporter Cholinergic phenotype Amyloid-β (25–35)