Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice

Dustin H. Brewton, Jamiela Kokash, Oliva Jimenez, Eloy R. Pena, Khaleel A. Razak

Age-related changes in inhibitory neurotransmission in sensory cortex may underlie deficits in sensory function. Perineuronal nets (PNNs) are extracellular matrix components that ensheath some inhibitory neurons, particularly parvalbumin positive (PV+) interneurons. PNNs may protect PV+ cells from oxidative stress and help establish their rapid spiking properties. Although PNN expression has been well characterized during development, possible changes in aging sensory cortex have not been investigated. Here we tested the hypothesis that PNN+, PV+ and PV/PNN co-localized cell densities decline with age in the primary auditory cortex (A1). This hypothesis was tested using immunohistochemistry in two strains of mice (C57BL/6 and CBA/CaJ) with different susceptibility to age-related hearing loss and at three different age ranges (1-3, 6-8 and 14-24 months old). We report that PNN+ and PV/PNN co-localized cell densities decline significantly with age in A1 in both mouse strains. In the PNN+ cells that remain in the old group, the intensity of PNN staining is reduced in the C57 strain, but not the CBA strain. PV+ cell density also declines only in the C57, but not the CBA, mouse suggesting a potential exacerbation of age-effects by hearing loss in the PV/PNN system. Taken together, these data suggest that PNN deterioration may be a key component of altered inhibition in the aging sensory cortex, that may lead to altered synaptic function, susceptibility to oxidative stress and processing deficits.