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Calvano, M.

Publications and source records attributed to Calvano, M..

2 recordsLinked to original sources

Noise-induced hearing loss delays auditory learning and reduces the influence of acoustic evidence on choice

Noise-induced hearing loss (NIHL) degrades auditory sensitivity, but how it affects the learning of sound-guided decisions remains unclear. We trained adult Mongolian gerbils with normal-hearing (NH) or permanent NIHL, induced by a 2-hour exposure to 120 dB SPL broadband noise, to discriminate 4- versus 12-Hz amplitude-modulated (AM) broadband noise presented in a two-alternative forced-choice task. Stimuli were presented at comparable sensation levels across groups. Relative to NH animals, NIHL animals required approximately 2.5 times more sessions and 2.9 times more trials to reach task acquisition criterion. This learning delay was not explained by reduced task engagement, response latency, or auditory brainstem response threshold shift. Video tracking showed that spatial occupancy refined with training in both groups, whereas trial-by-trial movement path trajectories became less variable in NH animals. Per-session and dynamic trial-by-trial logistic regression models revealed that the influence of the task-relevant acoustic stimulus increased with training in both groups but remained consistently lower in NIHL animals, whereas sound-independent choice tendencies were largely unchanged. Together, these results suggest that NIHL delays auditory learning by reducing the influence of acoustic evidence on choice, indicating that hearing loss can alter how sensory experience is used to acquire new behaviors.

animal behavior and cognition↗

Lecanemab Blocks the Effects of the Aβ/Fibrinogen Complex on Blood Clots and Synapse Toxicity in Organotypic Culture

Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimers disease (AD). Vascular deficits include a compromised blood-brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogens interaction with the amyloid-beta (A{beta}) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, shows promising results in facilitating reduction of A{beta} from the brain and slowing cognitive decline. Here we show that lecanemab blocks fibrinogens binding to A{beta} protofibrils, normalizing A{beta}/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the A{beta}/fibrinogen complex and prevents fibrinogen from exacerbating A{beta}-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.

biochemistry↗