Electrophysiological characterization of P300 event-related potentials in a rat model of Alzheimer's disease
Translated title
Electrophysiological characterization of P300 event-related potentials in a rat model og Alzheimer's disease
Author
Ahlbeck, Joachim
Term
4. term
Publication year
2012
Submitted on
2012-06-01
Pages
87
Abstract
Baggrund: Alzheimers sygdom er en uhelbredelig, fremadskridende hjernelidelse, der medfører tab af hukommelse, tænkning og kropslige funktioner. Den er forbundet med ophobning af giftige proteinfragmenter og svækkelse af det kolinerge signalsystem i hjernen. Forskere måler ofte hjernens elektriske svar på ydre hændelser (begivenhedsrelaterede potentialer, ERP’er) med elektroencefalografi (EEG). Et særligt svar, P300, hænger sammen med opmærksomhed og arbejdshukommelse og er ofte svækket eller forsinket hos personer med Alzheimers sygdom. En pålidelig P300-model i rotter kan derfor understøtte udviklingen af lægemidler, der retter sig mod kognition. Metoder: Vi registrerede ERP’er med EEG i hippocampus, auditiv cortex, parietal cortex og frontal/prelimbisk cortex hos rotter, mens de deltog i lydopgaver. På tværs af tre forsøg (to forsøgsopsætninger) analyserede vi tre typer sessioner: (1) en passiv sensorisk tilstand uden krav om at skelne mellem toner, (2) en diskriminationsopgave, hvor rotterne lærte at skelne mellem to toner, og (3) den samme diskriminationsopgave efter behandling med scopolamin (0,1 mg/kg) eller saltvand. Resultater: Der kunne ikke identificeres en P300 i den første tilstand. Under diskriminationstræning opstod der en tydelig P300 i hippocampus i forsøg 2 og 3 og i prelimbisk cortex i forsøg 3, med en latenstid på 170–180 ms. Scopolamin forøgede P300-latenstiden i hippocampus i forsøg 2, på linje med, hvad man ser hos mennesker. Dette tyder på, at den observerede rotte-P300 er overførbar til den menneskelige P300. Konklusion: Vi etablerede en metode til at fremkalde en P300 i rotter. Den hippocampale P300 ligner menneskers P300 og kan bruges til at undersøge nye stoffer, der påvirker kognitive funktioner ved Alzheimers sygdom. Prelimbisk cortex viste også en tendens til at efterligne menneskelig P300, men dette kræver yderligere validering.
Background: Alzheimer’s disease is an incurable, progressive brain disorder that leads to loss of memory, thinking, and bodily functions. It is linked to the buildup of toxic protein fragments and degeneration of the cholinergic signaling system. Researchers often use electroencephalography (EEG) to record event-related potentials (ERPs), brief electrical responses to stimuli that provide an objective window into brain processing. The P300 response, associated with attention and working memory, is frequently reduced or delayed in people with Alzheimer’s disease. A reliable rat model of P300 could therefore help in developing medicines that target cognition. Methods: We recorded ERPs with EEG from the hippocampus, auditory cortex, parietal cortex, and frontal/prelimbic cortex in rats while they performed sound tasks. Across three experiments (two setups), we analyzed three types of sessions: (1) a passive sensory condition with no tone discrimination, (2) a discrimination task in which rats learned to tell two tones apart, and (3) the same discrimination task after treatment with scopolamine (0.1 mg/kg) or saline. Results: No P300 was identified in the first condition. During discrimination training, a clear P300 emerged in the hippocampus in experiments 2 and 3 and in the prelimbic cortex in experiment 3, with a latency of 170–180 ms. Scopolamine increased P300 latency in the hippocampus in experiment 2, similar to patterns seen in humans. This supports the idea that the rat P300 observed here is translatable to the human P300. Conclusion: We established a method to evoke a P300 in rats. The hippocampal P300 shares key features with the human P300 and can be used to study new compounds that affect cognitive function in Alzheimer’s disease. The prelimbic cortex also showed a human-like pattern, but further studies are needed to validate this.
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