Isoproterenol injected into the basolateral amygdala rescues amyloid β1-42-induced conditioned fear memory deficit via reducing intracellular Zn2+ toxicity. (1st January 2022)

• Record Type: Journal Article
• Authors: Ishikawa, Yudai; Itoh, Ryusei; Tsujimoto, Rin; Tamano, Haruna; Takeda, Atsushi
• Is Part Of: Neuroscience letters. Volume 766(2022)
• Publication Date: 2022-01-01
• Subjects: Amyloid β1-42 -- Fear memory -- Zn2+ dysregulation -- Adrenergic β receptor -- Isoproterenol -- Basolateral amygdala; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2021.136353
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Injection of Aβ1-42 into the basolateral amygdala causes fear memory deficit. The memory deficit is linked with Aβ1-42 -induced intracellular Zn 2+ toxicity. Co-injection of isoproterenol rescues the memory deficit. Co-injection of isoproterenol reduces Aβ1-42 -induced intracellular Zn 2+ toxicity. Adrenergic β receptor activation is of benefit to the limbic system exposed to Aβ1-42 . Abstract: On the basis of amyloid β (Aβ) peptides as triggers in atrophy of structures in the limbic system, here we postulated that Aβ1-42 -induced intracellular Zn 2+ toxicity in the basolateral amygdala contributes to conditioned fear memory. Aβ1-42 increased intracellular Zn 2+ level in the amygdala after local injection of Aβ1-42 into the basolateral amygdala, resulting in conditioned fear memory deficit via attenuated LTP at perforant pathway-basolateral amygdala synapses. Co-injection of isoproterenol, a beta-adrenergic receptor agonist, reduced Aβ1-42 -mediated increase in intracellular Zn 2+, resulting in rescue of the memory deficit and attenuated LTP. The present study suggests that beta-adrenergic activity induced by isoproterenol in the basolateral amygdala rescues the impairment of conditioned fear memory by Aβ1-42 . The rescuing effect may be linked with reducing Aβ1-42 -induced intracellular Zn 2+ toxicity. Furthermore, Aβ1-42 injection into the basolateral amygdala also attenuated LTP at perforant pathway-dentate granule cell synapses, while co-injection of isoproterenol rescued it, suggesting that Aβ1-42 toxicity in the basolateral amygdala also affects hippocampus-dependent memory. It is likely that beta-adrenergic receptor activation in the basolateral amygdala rescues the limbic system exposed to Aβ1-42 toxicity.