The effects of magnesium ions on theglutamatergic system in the animal models ofdepression


Pochwat, Bartłomiej


AMPA ; magnesium ; NMDA ; depression ; BDNF


The determination of antidepressant-like activity of magnesium in the chronic mild stress and olfactory bulbectomythe animal models of depression was the main objective of these studies. Studies were conducted on Wistar male rats (chronic mild stress) and Sprague-Dawley male rats (olfactory bulbectomy). The antidepressant-like activity of magnesium in the chronic mild stress model was measured in the sucrose solution intake test. For evaluation of antidepressant-like activity of magnesium in the olfactory bulbectomy model the passive avoidance and open field tests were used. The expression of chosen proteins and mRNA of molecules' engaged in the functioning of glutamate system were determinated respectively by western blotting and RT-PCR methods. Magnesium at a dose of 15mgMg/kg reversed reduction in the sucrose solution intake evoke by chronic mild stress after 3 weeks of treatment. Administration of magnesium at doses of 15 and 20 mgMg/kg significantly improved ability to acquisition of passive avoidance reflex in OB rats. In the open field test all used doses (10, 15 i 20 mgMg/kg) of magnesium reduced hyperactivity induced by bulbectomy. After chronic mild stress increased levels of GluN 1 subunit of NMDA receptors and GluA 1 subunit of AMPA receptors in amygdala were observed. These changes were accompanied by elevated level of BDNF. All of these alterations were reversed b ; y chronic magnesium treatment. Furthermore, magnesium administration in stressed rats led to the increase level of GluN28 subunit of NMDA receptor and PSD-95, compare to control stress animals. Removal of olfactory bulbs induced a decreased level of GAD-67 in PFC and reduced level of P-S845 of GluA 1 subunit of AMPA receptors in the hippocampus. Chronic administration of magnesium at a dose of 15mgMg/kg reversed these changes. Two weeks of magnesium treatment in OB rats led to enhanced P-S831 and P-S845 of GluA 1 subunit of AMPA receptors in PFC, compare to 08 rats treated by NaCI. Concomitantly the BDNF level in PFC after magnesium treatment was also increased compare to 0B Nacl rats. The enhanced expression of BDNF after magnesium treatment in OB rats was also noticed in amygdala and hippocampus. In amygdala of 0B rats chronically treated with magnesium also elevated level of GluN2B subunit of NMDA receptors was found. In PFC of 0B animals decreased levels of mRNA of MT 1, 2 and 3 were observed. Chronic magnesium treatment normalized level of mRNA of MT 1 and MT 2. The results obtained in this PhD thesis provide further, preclinical evidence for the antidepressant-like activity of magnesium. Antidepressant-like activity of magnesium showed in two animal model of depression is very important argument for potential utility of magnesium in treatment of clinical depression. Addit ; ionally, biochemical assays let agree that the antidepressant-like activity of magnesium may involve NMDA/AMPA/BDNF pathways.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

farmakologia ; psychiatria

Degree grantor:

Wydział Farmaceutyczny


Nowak, Gabriel ; Szewczyk, Bernadeta



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Praca doktorska

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