Hippocampal chloride transporter KCC2 contributes to excitatory GABA dysregulation in the developmental rat model of schizophrenia
| Autor: | Soraya Mehrabi, Nida Jamali-Raeufy, Mehrnoosh Arabi, Alireza Susanabadi, Pezhman Atefimanash, Reza Rahmanzadeh, Ramin Rahmanzadeh, Mahsa Pourhamzeh |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Prefrontal Cortex Hippocampus Hippocampal formation Biology Rats Sprague-Dawley Cellular and Molecular Neuroscience Internal medicine medicine Animals Diuretics Prefrontal cortex Bumetanide gamma-Aminobutyric Acid Prepulse inhibition Symporters Prepulse Inhibition Transporter medicine.disease Rats Endocrinology Social Isolation Schizophrenia Excitatory postsynaptic potential medicine.drug |
| Zdroj: | Journal of Chemical Neuroanatomy. 118:102040 |
| ISSN: | 0891-0618 |
| DOI: | 10.1016/j.jchemneu.2021.102040 |
| Popis: | Recent studies have revealed an altered expression of NKCC1 and KCC2 in prefrontal cortex (PFC) and hippocampus of schizophrenic patients. Despite extensive considerations, the alteration of NKCC1 and KCC2 co-transporters at different stages of development has not been fully studied. Therefore, we evaluated the expression of these transporters in PFC and hippocampus at time points of four, eight, and twelve weeks in post-weaning social isolation rearing rat model. For this purpose, 23-25 days-old rats were classified into social- or isolation-reared groups. The levels of NKCC1 and KCC2 mRNA expression were evaluated at hippocampus or PFC regions at the time-points of four, eight, and twelve weeks following housing. Post-weaning isolation rearing decreased the hippocampal KCC2 mRNA expression level, but does not affect the NKCC1 mRNA expression. However, no significant difference was observed in the PFC mRNA levels of NKCC1 and KCC2 in the isolation-reared group compared to the socially-reared group during the course of modeling. Further, we assessed the therapeutic effect of selective NKCC1 inhibitor bumetanide (10 mg/kg), on improvement of prepulse inhibition (PPI) test on twelve weeks isolation-reared rats. Intraperitoneal administration of bumetanide (10 mg/kg) did not exert beneficial effects on PPI deficit. Our findings show that isolation rearing reduces hippocampal KCC2 expression level and may underlie hippocampal GABA excitatory. In addition, 10 mg/kg bumetanide is not effective in improving the reduced PPI of twelve weeks isolation-reared rats. Collectively, our findings show that hippocampal chloride transporter KCC2 contributes to excitatory GABA dysregulation in the developmental rat model of schizophrenia. |
| Databáze: | OpenAIRE |
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