Adrenergic β receptor activation reduces amyloid β1-42-mediated intracellular Zn2+ toxicity in dentate granule cells followed by rescuing impairment of dentate gyrus LTP
| Autor: | Haruna Tamano, Atsushi Takeda, Ashley I. Bush, Ryusei Itoh, Mako Egawa, Yudai Ishikawa, Paul A. Adlard, Ryota Shimaya, Aoi Shioya, Naoya Oneta |
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| Rok vydání: | 2020 |
| Předmět: |
Agonist
0303 health sciences medicine.medical_specialty Chemistry medicine.drug_class General Neuroscience Dentate gyrus Adrenergic Long-term potentiation Toxicology Granule cell Adrenergic beta-Antagonists 03 medical and health sciences 0302 clinical medicine Endocrinology medicine.anatomical_structure Internal medicine medicine Receptor 030217 neurology & neurosurgery Intracellular 030304 developmental biology |
| Zdroj: | NeuroToxicology. 79:177-183 |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2020.06.001 |
| Popis: | Adrenergic β receptor activation prevents human soluble amyloid β (Aβ)-induced impairment of long-term potentiation (LTP) in slices. On the basis of the evidence that human Aβ1-42-induced impairment of LTP is due to Aβ1-42-mediated Zn2+ toxicity, we postulated that adrenergic β receptor activation reduces Aβ1-42-mediated intracellular Zn2+ toxicity followed by rescuing Aβ1-42 toxicity. To test the effect of adrenergic β receptor activation, LTP was recorded at perforant pathway-dentate granule cell synapses of anesthetized rats 60 min after Aβ1-42 injection into the dentate granule cell layer. Human Aβ1-42-induced impairment of LTP was rescued by co-injection of isoproterenol, an adrenergic β receptor agonist, but not by co-injection of phenylephrine, an adrenergic α1 receptor agonist. Isoproterenol did not reduce Aβ1-42 uptake into dentate granule cells, but reduced increase in intracellular Zn2+ in dentate granule cells induced by Aβ1-42. In contrast, phenylephrine did not reduce both Aβ1-42 uptake and increase in intracellular Zn2+ by Aβ1-42. In the case of human Aβ1-40 and rat Aβ1-42, which do not increase intracellular Zn2+, human Aβ1-40- and rat Aβ1-42-induced impairments of LTP were not rescued by co-injection of isoproterenol. The present study indicates that adrenergic β receptor activation reduces Aβ1-42-mediated increase in intracellular Zn2+ in dentate granule cells, resulting in rescuing Aβ1-42-induced impairment of LTP. It is likely that noradrenergic neuron activation by stimulating the locus coeruleus is effective for rescuing Aβ1-42-induced cognitive decline that is caused by intracellular Zn2+ dysregulation in the hippocampus. |
| Databáze: | OpenAIRE |
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