Co-expression analysis identifies neuro-inflammation as a driver of sensory neuron aging in Aplysia californica

Abstract

Aging of the nervous system is typified by depressed metabolism, compromised proteostasis, and increased inflammation that results in cognitive impairment. Differential expression analysis is a popular technique for exploring the molecular underpinnings of neural aging, but technical drawbacks of the methodology often obscure larger expression patterns. Co-expression analysis offers a robust alternative that allows for identification of networks of genes and their putative central regulators. In an effort to expand upon previous work exploring neural aging in the marine model Aplysia californica, we used weighted gene correlation network analysis to identify co-expression networks in a targeted set of aging sensory neurons in these animals. We identified twelve modules, six of which were strongly positively or negatively associated with aging. Kyoto Encyclopedia of Genes analysis and investigation of central module transcripts identified signatures of metabolic impairment, increased reactive oxygen species, compromised proteostasis, disrupted signaling, and increased inflammation. Although modules with immune character were identified, there was no correlation between genes in Aplysia that increased in expression with aging and the orthologous genes in oyster displaying long-term increases in expression after a virus-like challenge. This suggests anti-viral response is not a driver of Aplysia sensory neuron aging.

Improvements in operant memory of Aplysia are correlated with age and specific gene expression

“…Animal age in this study was determined by the chronological age as well as the significant decline in performance of reflex behaviors beginning at the age of 12 months ( Figure 2 ). Our laboratory demonstrated that performance in these behaviors declines in a predictable manner with age ( Kempsell and Fieber, 2014 ) and that declining performance is accompanied by a decline in excitability of PVC sensory neurons that control tail withdrawal, decreased short-term facilitation (STF) between tail sensory and motor neurons ( Kempsell and Fieber, 2015 ), decreased expression of ionotropic glutamate receptor subunits ( Greer et al, 2019 ), and other changes in gene expression that alter proteostasis and increase neuro-inflammation ( Kron et al, 2020 ; Kron and Fieber, 2021 ).…”

In search of the Aplysia immunome: an in silico study

“…However, the dearth of functional annotation and lack of even a putative immune gene set makes future inference into the immune response to this novel virus difficult. While some putative immune associated genes have been identified in Aplysia previously in the context of the neuronal transcriptome [14] or aging associated neuro-inflammation [21], these studies did not perform a comprehensive survey of the Aplysia immunome. To address this gap in the Aplysia literature, an in silico survey of Aplysia reference genome was conducted to identify and describe a putative immunome to aid in future immunological studies in this well-established model.…”