IMPAIRMENTS OF HIPPOCAMPAL LTP BY INTRACEREBRAL INOCULATION WITH OLIGOMERIC ABETA(1-42) ARE EXACERBATED BY AGE-RELATED HEARING LOSS IN MICE

Age-related hearing loss (ARHL) is considered a risk factor for Alzheimer's disease (AD)(10.3389/fnins.2018.00394) and mice that have congenital ARHL exhibit both deficits in hippocampal synaptic plasticity and spatial learning (10.1093/cercor/bhaa061; 10.1098/rstb.2023.0229). Hippocampal function is debilitated by intracerebral inoculation with oligomeric amyloid-beta (Abeta1-42) (10.3389/fnbeh.2015.00103) that is regarded as one of the main instigators of AD (10.12659/MSM.933084; 10.1111/febs.1693; 10.1016/j.immuni.2024.09.014).
Here, we explored the extent to which hippocampal synaptic plasticity is affected by ARHL and Abeta. Two mouse strains were compared: the C57BL/6 strain that exhibits progressive ARHL from early life (10.3342/ceo.2010.3.3.126), and the CBA/CaOlaHsd that does not exhibit sensory deficits.
Male mice underwent intracerebral inoculation with oligomeric Abeta(1-42) at 2 months of age. One, three, and six months later, hippocampal long-term potentiation (LTP) was assessed in freely behaving mice. We observed that C57BL/6 mice expressed weaker LTP compared to age-matched CBA/CaOlaHsd mice. Moreover, the ARHL strain exhibited impaired LTP, compared to controls, beginning one month after treatment. By contrast, CBA/CaOla mice first exhibited impaired LTP 6 months after treatment with Abeta. These results indicate that ARHL may be associated with poorer hippocampal synaptic plasticity in mice. In addition, LTP impairments, caused by intracerebral inoculation with oligomeric Abeta, emerge in earlier in time in ARHL mice than in the sensorily intact murine strain. These findings prompt further considerations that a functional link between Abeta(1-42) propagation and ARHL may contribute to the increased AD vulnerability of individuals suffering from ARHL.
Supported by a Deutsche Forschungsgemeinschafts grant to DMV (GRK 2862/P04, project no.: 492434978).