The Density of Perineuronal Nets Increases With Age in the Inferior Colliculus in the Fischer Brown Norway Rat

Abstract

Age-related hearing loss, one of the most frequently diagnosed disabilities in industrialized countries, may result from declining levels of GABA in the aging inferior colliculus (IC). However, the mechanisms of aging and subsequent disruptions of temporal processing in elderly hearing abilities are still being investigated. Perineuronal nets (PNs) are a specialized form of the extracellular matrix and have been linked to GABAergic neurotransmission and to the regulation of structural and synaptic plasticity. We sought to determine whether the density of PNs in the IC changes with age. We combined Wisteria floribunda agglutinin (WFA) staining with immunohistochemistry to glutamic acid decarboxylase in three age groups of Fischer Brown Norway (FBN) rats. The density of PNs on GABAergic and non-GABAergic cells in the three major subdivisions of the IC was quantified. Results first demonstrate that the density of PNs in the FBN IC increase with age. The greatest increases of PN density from young to old age occurred in the central IC (67% increase) and dorsal IC (117% increase). Second, in the young IC, PNs surround non-GABAergic and GABAergic cells with the majority of PNs surrounding the former. The increase of PNs with age in the IC occurred on both non-GABAergic and GABAergic populations. The average density of PN-surrounded non-GABAergic cells increased from 84.9 PNs/mm 2 in the young to 134.2 PNs/mm 2 in the old. While the density of PN-surrounded GABAergic cells increased from 26 PNs/mm 2 in the young to 40.6 PNs/mm 2 in the old. The causality is unclear, but increases in PN density in old age may play a role in altered auditory processing in the elderly, or may lead to further changes in IC plasticity.

Microglia as hackers of the matrix: sculpting synapses and the extracellular space

“…It should be noted that several studies failed to detect differences in PNN abundance in clinical AD [202][203][204][205], and this may be partly attributable to the brain region under investigation or the method of PNN labeling used. While changes with non-diseased aging are less clear [90,[206][207][208], we and others have found age-related reductions in PNN density in older animals [90,193,208,209], and discrepancies across studies may depend on the inclusion of both sexes and the brain region(s), mouse strain, and/or model organism being studied.…”

Impact of Perineuronal Nets on Electrophysiology of Parvalbumin Interneurons, Principal Neurons, and Brain Oscillations: A Review

“…Two studies have shown circadian/diurnal changes, with higher numbers or intensity of PNNs in the dark phase in rodents (Pantazopoulos et al, 2020 ; Harkness et al, 2021 ). Given that PNNs are altered in many ways throughout central nervous system development, and their maturation is brain region-specific and generally coincides with the end of critical periods of plasticity (for a recent review see Carulli and Verhaagen, 2021 ), it is not surprising that numerous studies have also demonstrated changes in PNNs or their composition during aging (Tanaka and Mizoguchi, 2009 ; Karetko-Sysa et al, 2014 ; Brewton et al, 2016 ; Foscarin et al, 2017 ; Richard et al, 2018 ; Ueno et al, 2019 ; Mafi et al, 2020 ). Overall, changes in PNNs and PV neurons after physiological stimuli appear to be specific to the physiological stimulus, brain region, and the circuits in which PNN-surrounded neurons are embedded.…”

Corticothalamic projections deliver enhanced responses to medial geniculate body as a function of the temporal reliability of the stimulus

“…FBN rats have a long life span and lower tumour load than other commonly used rat ageing models. They have been characterized as a rat model of ageing (Cai et al 2018), and age-related changes in their central auditory structures have been extensively studied (Caspary et al 2008;Caspary & Llano, 2019;Mafi et al 2020).…”