Amyloid fibrils induce dysfunction of hippocampal glutamatergic silent synapses
Copyright policy )Amyloid fibrils induce dysfunction of hippocampal glutamatergic silent synapses
AbstractSilent glutamatergic synapses lacking functional AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionate) receptors exist in several brain regions including the hippocampus. Their involvement in the dysfunction of hippocampal glutamatergic transmission in the setting of Alzheimer's disease (AD) is unknown. This study demonstrated a decrease in the percentage of silent synapses in rats microinjected with amyloid fibrils (Aβ1–40) into the hippocampal CA1. Also, pairing low‐frequency electric stimuli failed to induce activation of the hippocampal silent synapses in the modeled rats. Immunoblotting studies revealed a decreased expression of GluR1 subunits in the hippocampal CA1 synaptosomal preparation, indicating a potential reduction in the GluR1 subunits anchoring in postsynaptic density in the modeled rats. We also noted a decreased expression of phosphorylated cofilin, which regulates the function of actin cytoskeleton and receptor trafficking, and reduced expression of the scaffolding protein PSD95 in the hippocampal CA1 synaptosome in rats injected with Aβ1–40. Taken together, this study illustrates dysfunction of hippocampal silent synapse in the rodent model of AD, which might result from the impairments of actin cytoskeleton and postsynaptic scaffolding proteins induced by amyloid fibrils.
- Case Western Reserve University United States
- Cleveland Clinic Lerner College of Medicine United States
Cofilin 1, Male, Amyloid, Memory Disorders, Amyloid beta-Peptides, Patch-Clamp Techniques, Long-Term Potentiation, Glutamic Acid, In Vitro Techniques, Electric Stimulation, Peptide Fragments, Rats, Rats, Sprague-Dawley, Disease Models, Animal, Gene Expression Regulation, Animals, Receptors, AMPA, Maze Learning, CA1 Region, Hippocampal, Disks Large Homolog 4 Protein
Cofilin 1, Male, Amyloid, Memory Disorders, Amyloid beta-Peptides, Patch-Clamp Techniques, Long-Term Potentiation, Glutamic Acid, In Vitro Techniques, Electric Stimulation, Peptide Fragments, Rats, Rats, Sprague-Dawley, Disease Models, Animal, Gene Expression Regulation, Animals, Receptors, AMPA, Maze Learning, CA1 Region, Hippocampal, Disks Large Homolog 4 Protein
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