title: Age-related synaptic dysfunction in Tg2576 mice starts as a failure in early long-term potentiation which develops into a full abolishment of late long-term potentiation.
abstract: Tg2576 mice are widely used to study amyloid-dependent synaptic dysfunction related to Alzheimer's disease. However, conflicting data have been reported for these mice with regard to basal transmission as well as the in vitro correlate of memory, long-term potentiation (LTP). Some studies show clear impairments, whereas others report no deficiency. The present study uses hippocampal slices from 3-, 10-, and 15-month-old wild-type (WT) and Tg2576 mice to evaluate synaptic function in each group, including experiments to investigate basal synaptic transmission, short- and long-term plasticity by inducing paired-pulse facilitation, and both early and late LTP. We show that synaptic function remains intact in hippocampal slices from Tg2576 mice at 3 months of age. However, both early and late LTP decline progressively during aging in these mice. This deterioration of synaptic plasticity starts affecting early LTP, ultimately leading to the abolishment of both forms of LTP in 15-month-old animals. In comparison, WT littermates display normal synaptic parameters during aging. Additional pharmacological investigation into the involvement of NMDA receptors and L-type voltage-gated calcium channels in LTP suggests a distinct mechanism of induction among age groups, demonstrating that both early and late LTP are differentially affected by these channels in Tg2576 mice during aging.
authors.affiliation: Deparment of CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach (Riss), Germany.
authors.forename: Diego
authors.initials: D
authors.lastname: Fernández-Fernández
authors.affiliation: Deparment of CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach (Riss), Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dorner-Ciossek
authors.affiliation: Deptartment of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach (Riss), Germany.
authors.forename: Katja S
authors.initials: KS
authors.lastname: Kroker
authors.affiliation: Deparment of CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach (Riss), Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Rosenbrock
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001703:Biophysics; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D018691:Excitatory Amino Acid Antagonists; D053764:Presenilin-1; D016291:Dizocilpine Maleate
keywords: Alzheimer's disease; fEPSP; hippocampus; paired-pulse facilitation; synaptic plasticity