2014
DOI: 10.1038/mp.2014.87
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Proneurogenic Group II mGluR antagonist improves learning and reduces anxiety in Alzheimer Aβ oligomer mouse

Abstract: Proneurogenic compounds have recently shown promise in some mouse models of Alzheimer's pathology. Antagonists at Group II metabotropic glutamate receptors (Group II mGluR: mGlu2, mGlu3) are reported to stimulate neurogenesis. Agonists at those receptors trigger γ-secretase-inhibitor-sensitive biogenesis of Aβ42 peptides from isolated synaptic terminals, which is selectively suppressed by antagonist pretreatment. We have assessed the therapeutic potential of chronic pharmacological inhibition of Group II mGluR… Show more

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Cited by 56 publications
(50 citation statements)
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“…Both cholinergic and GABAergic cell loss in the brain of these transgenic mice, in the absence of parenchymal and vascular β amyloid deposition, implies a role for intracellular accumulation of APP-CTFs/oAβ in neuronal degeneration and subsequent impaired spatial learning and memory, novel object recognition, and increased anxiety in APP E693Q transgenic mice 17, 3941 .…”
Section: Discussionmentioning
confidence: 97%
“…Both cholinergic and GABAergic cell loss in the brain of these transgenic mice, in the absence of parenchymal and vascular β amyloid deposition, implies a role for intracellular accumulation of APP-CTFs/oAβ in neuronal degeneration and subsequent impaired spatial learning and memory, novel object recognition, and increased anxiety in APP E693Q transgenic mice 17, 3941 .…”
Section: Discussionmentioning
confidence: 97%
“…; Kim et al . ; Pitsikas ). Fyn‐deficient mice showed heightened anxiety‐like behaviors (Miyakawa et al .…”
Section: Discussionmentioning
confidence: 99%
“…The rationale for studying group II mGluR function is that they have been drug targets for anxiety disorders and depression as well as for cognitive deficits in neurodegenerative and neuropsychiatric disorders [12;22;28;36;37]. Pain is associated with affective and cognitive dysfunctions as well [3;30;34], and group II mGluR agonists have antinociceptive effects at different levels of the pain neuraxis, including nociceptors [7;32], spinal dorsal horn neurons [33;45] and amygdala [1;25].…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, group II mGluR antagonists and negative allosteric modulators also showed antidepressant effects and in particular on outcome measures of cognitive dysfunction [2;6;12;37], possibly involving the prefrontal cortex [2]. Group II mGluR antagonists had beneficial effects in an Alzheimer's Disease mouse model, improving cognitive functions and anxiety [22]. However, mGluR3 negative allosteric modulators impaired extinction of conditioned fear [43].…”
Section: Introductionmentioning
confidence: 99%