Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function.

Autor: Ntoulas G; Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina, Ioannina, Greece., Brakatselos C; Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina, Ioannina, Greece., Nakas G; Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina, Ioannina, Greece., Asprogerakas MZ; Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina, Ioannina, Greece., Delis F; Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina, Ioannina, Greece., Leontiadis LJ; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Trompoukis G; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Papatheodoropoulos C; Laboratory of Neurophysiology, Department of Medicine, University of Patras, Rion, Greece., Gkikas D; Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Valakos D; Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Vatsellas G; Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Politis PK; Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Polissidis A; Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina, Ioannina, Greece.; Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Antoniou K; Department of Pharmacology, Faculty of Medicine, School of Health Sciences University of Ioannina, Ioannina, Greece. kantoniou@uoi.gr.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Feb 20; Vol. 14 (1), pp. 104. Date of Electronic Publication: 2024 Feb 20.
DOI: 10.1038/s41398-024-02815-0
Abstrakt: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard. Therefore, we employed a multi-level approach to study the behavioral profile and the glutamatergic and GABAergic neurotransmission status in pathophysiology-associated brain structures of Fmr1 KO rats, including the recordings of evoked and spontaneous field potentials from hippocampal slices, paralleled with next-generation RNA sequencing (RNA-seq). We found that these rats exhibit hyperactivity and cognitive deficits, along with characteristic bidirectional glutamatergic and GABAergic alterations in the prefrontal cortex and the hippocampus. These results are coupled to affected excitability and local inhibitory processes in the hippocampus, along with a specific transcriptional profile, highlighting dysregulated hippocampal network activity in KO rats. Overall, our data provide novel insights concerning the biobehavioral profile of FmR1 KO rats and translationally upscales our understanding on pathophysiology and symptomatology of FXS syndrome.
(© 2024. The Author(s).)
Databáze: MEDLINE
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