Abstract

Aging affects the overall physiology, including the image-forming and non-image forming visual systems. Among the components of the latter, the thalamic retinorecipient inter-geniculate leaflet (IGL) and ventral lateral geniculate (vLGN) nucleus conveys light information to subcortical regions, adjusting visuomotor, and circadian functions. It is noteworthy that several visual related cells, such as neuronal subpopulations in the IGL and vLGN are neurochemically characterized by the presence of calcium binding proteins. Calretinin (CR), a representative of such proteins, denotes region-specificity in a temporal manner by variable day–night expression. In parallel, age-related brain dysfunction and neurodegeneration are associated with abnormal intracellular concentrations of calcium. Here, we investigated whether daily changes in the number of CR neurons are a feature of the aged IGL and vLGN in rats. To this end, we perfused rats, ranging from 3 to 24 months of age, within distinct phases of the day, namely zeitgeber times (ZTs). Then, we evaluated CR immunolabeling through design-based stereological cell estimation. We observed distinct daily rhythms of CR expression in the IGL and in both the retinorecipient (vLGNe) and non-retinorecipient (vLGNi) portions of the vLGN. In the ZT 6, the middle of the light phase, the CR cells are reduced with aging in the IGL and vLGNe. In the ZT 12, the transition between light to dark, an age-related CR loss was found in all nuclei. While CR expression predominates in specific spatial domains of vLGN, age-related changes appear not to be restricted at particular portions. No alterations were found in the dark/light transition or in the middle of the dark phase, ZTs 0, and 18, respectively. These results are relevant in the understanding of how aging shifts the phenotype of visual related cells at topographically organized channels of visuomotor and circadian processing.

Highlights

  • Aging is characterized, for most living organisms, as a timedependent physiological decline associated with increases in mortality and decreases in fertility rates (Flatt and Partridge, 2018)

  • After employing the two-way ANOVA with light condition as an isolated factor, we observed a significant effect upon CR neuronal changes in the inter-geniculate leaflet (IGL) [F(3,36) = 4.07; p = 0.01], vLGN in an external retinorecipient (vLGNe) [F(3,36) = 4.82; p = 0.006], and Ventral lateral geniculate nucleus internal portion (vLGNi) [F(3,36) = 5.99; p = 0.002]

  • We describe how changes in the daily expression of the calcium binding protein, CR, marks region-specific patterns of cellular aging in the rat non-image forming visual thalamus

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Summary

Introduction

For most living organisms, as a timedependent physiological decline associated with increases in mortality and decreases in fertility rates (Flatt and Partridge, 2018). For instance, despite there being few changes in the global neuronal numbers throughout life (Long et al, 1999; von Bartheld et al, 2016), neurochemical-specific subpopulations of cells are lost during aging (Bañuelos et al, 2013; Pal et al, 2019; Lamerand et al, 2020). Given the diverse nature of brain neurochemistry, the characterization of age-related changes in a cellular level still poses a challenging endeavor for neuroscience. Protein-mediated mechanisms of cytosolic Ca2+ buffering, such as the action of the EF-hand family of calcium binding proteins (CaBPs), may act as neuroprotective factors influencing age-related alterations (Alzheimer’s Association Calcium Hypothesis Workgroup, 2017). The CR immunopositive (CR+) neurons are lost during aging in the cortical and subcortical regions of rodent and human brains (Villa et al, 1994; Bu et al, 2003; Bae et al, 2015; Ahn et al, 2017)

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