Neurodegeneration-related genes are differentially expressed in middle-aged rats compared to young-adult rats having equal performance on long-term memory and synaptic plasticity

• Published in: Brain research bulletin 2022-05, Vol.182, p.90-101
• Main Authors: Babur, Ercan, Tufan, Esra, Barutçu, Özlem, Aslan-Gülpınar, Ezgi, Tan, Burak, Süer, Cem, Dursun, Nurcan
• Format: Article
• Language: English
• Subjects: Aging; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Glycogen Synthase Kinase 3 beta; Hippocampus; Male; Memory, Long-Term; Neurodegeneration-related genes; Neurodegenerative Diseases - genetics; Neuronal Plasticity; Protein tau; Rats; Rats, Wistar; Synaptic plasticity
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2022.02.007

The present study is concerned with assessing differences in plasticity-induced neurodegeneration-related gene expressions and tau phosphorylation between young-aged and middle-aged rats. The experiments were carried out in vivo under urethane anesthesia on adult male Wistar rats between the ages of 2-3 months and 11-12 months. Field potentials, composed of a field of excitatory-postsynaptic potential (fEPSP) and a population-spike (PS), were recorded from granule cells of the dentate gyrus. Plasticity was induced by high-frequency (HFS) or low frequency stimulation (LFS). mRNA of neurodegeneration-related genes and total-and phosphorylated-tau were measured in HFS-and LFS-induced hippocampus by using quantitative rt-PCR and Western blotting. In addition, naive rats (unstimulated) were tested for spatial learning and memory with a 5-day Morris water maze (MWM). HFS-induced LTP of PS had attenuated in middle-aged rats, but there were no gross differences in baseline synaptic function, HFS-induced fEPSP and LFS-induced fEPSP, and PS plasticity between young-aged and middle-aged rats. Relative to young-aged rats, in middle-aged rats, HFS-induced MAPT, CDK5, and AKT1 genes were more up regulated, while LFS-induced Bace1, PSEN2, CAPN1, ANXA, CDK5, and GSK-3β genes were more down-regulated. Tau and p-tauThr231 were increased by HFS/LFS in the hippocampus of middle-aged rats compared to those of young-aged rats. In MWM, despite the difference in searching strategy of both age groups of rats, memory was not affected by age. Impaired long-term potentiation (LTP) and accompanying changes in intracellular biological markers may underlie in neurodegenerative disease characterized by dementia that occurs gradually later ages. However, these changes were not reflected in behavioral spatial memory. •Hippocampal memory and synaptic plasticity are not affected by aging to middle-age.•Somatic plasticity of the dentate gyrus can be attenuated in middle-aged rats.•Changes in plasticity-induced gene expression are different in middle-aged rats.•Aging to middle-age increases tau phosphorylation accompanying synaptic plasticity.•Plasticity-related molecular changes may trigger dementia observing in older ages.