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Identifier 000451424
Title Investigation of hippocampal function in a model of schizophrenia in neonatal ,juvenile, adolescent and adult period
Alternative Title Μελέτη της λειτουργίας του ιππόκαμπου σε ένα μοντέλο σχιζοφρένιας τη νεογνική νεανική εφηβική και ενήλικη περίοδο
Author Λυράκη, Όλγα
Thesis advisor Σιδηροπούλου, Κυριακή
Reviewer Καραγωγέως, Δόμνα
Χαραλαμπόπουλος, Ιωάννης
Abstract Schizophrenia is a major, severe and multifactorial neuropsychiatric disorder, for which current medications mainly focus on treating the positive symptoms of the disease. In our study we aim to identify early-life neurophysiological changes in the methylazoxymethanol acetate (MAM) mouse model of schizophrenia compared to control mice, in order to use them as biomarkers and help us develop effective treatments against all symptoms of the disease. Our experiments include neonatal (p8-12), juvenile (p18-25), adolescent (p38-45), adult (>p90) female and male C57BL/6J mice. MAM or control mice of all groups were decapitated and hippocampal (HPC) brain slices were acquired for extracellular local field recordings, followed by analysis for neuronal firing activity and neuronal oscillations. Moreover, adolescent MAM and control mice performed the novel object recognition task (NORT) and the object-to-place (OTP) task. Finally, juvenile, adolescent and adult MAM and control mice were additionally investigated for hippocampal pruning. In our results we observed a significant reduction regarding the baseline neuronal oscillations of delta, theta, alpha, beta and gamma rhythms in neonatal MAM mice, but not in juvenile or adolescent MAM mice, while only neonatal MAM mice exhibited decreased frequency of firing activity, compared to controls. Application of cannabidiol in HPC brain slices did not change the frequency of neuronal firing activity in MAM mice; however, in control neonatal mice, cannabidiol application in HPC brain slices increased the delta, theta, alpha, beta and gamma frequencies, whereas in MAM neonatal mice cannabidiol reduced the contribution of these frequencies. Adolescent and adult MAM mice exhibited increased pruning in mature dendritic spines in the hippocampus, while juvenile MAM mice exhibited a tendency toward increased pruning of immature spines. Finally, adolescent MAM mice exhibited a significantly reduced discrimination index compared to control mice in OTP task. Thus, early-life alterations of neuronal oscillations and firing activity could affect hippocampal development and lead to cognitive deficits (OTP deficits), which are further boosted by increased dendritic pruning, observed in adolescent MAM mice.
Language English
Subject Electrophysiological
Ηλεκτροφυσιολογική μελέτη
Issue date 2022-12-07
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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