Increased cell proliferation in the adult mouse hippocampus following chronic administration of group II metabotropic glutamate receptor antagonist, MGS0039
Section snippets
Materials and methods
Experimental animals. Male ICR mice, 8–10 weeks old (Charles River, Japan), were used for this study. All mice were housed in groups of 10 per cage, under standard conditions; room temperature (23 ± 3 °C); light–dark cycle (light phase 7:00–19:00). The mice were given free access to food and water except during the experiment. This study was conducted with the approval of Taisho Pharmaceutical Co., Ltd. Animal Care Committee.
Chemicals and drug administration. For chronic dosing, MGS0039 (5 or 10
Results and discussion
BrdU-labeled nuclei of proliferating cells were frequently observed in clusters, localized in the subgranular zone of the hippocampus in all treated mice (Fig. 1). In chronic fluvoxamine-treated animals, the total number of BrdU-positive cells in the dentate gyrus and hilus was 2019 ± 59 (mean ± SEM) compared with 1499 ± 75 in the vehicle group, which corresponds to a significant increase (35%) (p<0.001). Interestingly, chronic administration of MGS0039 at 5 and 10 mg/kg promoted progenitor cell
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Clinical investigations of compounds targeting metabotropic glutamate receptors
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2019, European Journal of PharmacologymGlu2/3 receptor antagonists
2019, Advances in PharmacologyCitation Excerpt :Consistent with these findings of vitro studies, chronic treatment with an mGlu2/3 receptor antagonist, MGS0210, for 3 months reversed transgene-related amnestic behavior, anxiety, as well as the brain Aβ monomer and oligomer levels in Dutch Aβ-oligomer-forming APP transgenic mice (APP E693Q) (Kim et al., 2014). Interestingly, 2-weeks treatment with MGS0039 significantly increased hippocampal neurogenesis in naïve mice (Yoshimizu & Chaki, 2004), and MGS0210 increased hippocampal neurogenesis more potently in Dutch APP mice than in wild-type (Kim et al., 2014). These findings are of particular interest, given the increased expression of the mGlu2 receptor in the regions and the cellular subtype of neural vulnerability to degeneration and neurofibrillary alterations in AD as compared to age-matched controls (Lee et al., 2004).
mGlu2/3 Receptor Antagonists as Novel Antidepressants
2017, Trends in Pharmacological SciencesCitation Excerpt :Given that mGlu2/3 receptor antagonists may also stimulate postsynaptic serotonin-1A receptor activity, likely by induction of serotonin release via AMPA receptor stimulation [60,61], AMPA receptor-mediated increases in serotonergic neural transmission (thereby stimulating postsynaptic serotonin-1A receptor activity) would be an important mechanism underlying not only the antidepressant effects, but also the pro-cognitive effects of mGlu2/3 receptor antagonists. Moreover, it was shown that repeated-dose administration of MGS0039 increased progenitor cell proliferation in the dentate gyrus of the hippocampus [82], indicative of increased hippocampal neurogenesis, which has also been proposed to be involved in the antidepressant effects of the drugs [83]. Increased hippocampal neurogenesis may have a positive impact on cognitive function, and this mechanism may also be involved in the pro-cognitive actions of mGlu2/3 receptor antagonists.