Linking the why and how of aging; evidence for somatotropic control of long-term memory function in the pond snail Lymnaea stagnalis

Abstract

Organisms live on a budget; hence, they cannot maximize all their activities at the same time. Instead, they must prioritize how they spend limiting resources on the many processes they rely on in their lives. Among others, they are thought to economize on the maintenance and repair processes required for survival in favour of maximizing reproduction, with ageing as a consequence. We investigate the biological mechanisms of neuronal ageing. Using Lymnaea stagnalis, we have previously described various aspects of age-associated neuronal decline and appetitive long-term memory failure. In view of postulated trade-offs between somatic maintenance and reproduction, we tested for interactions between resource allocation mechanisms and brain function. We show that removal of the lateral lobes, which are key regulators of energy balance in L. stagnalis, increases body mass and enhances appetitive learning, raising the possibility that the lateral lobes are one of the sites where the 'why' and 'how' of (neuronal) ageing meet.

The Great Pond Snail (Lymnaea stagnalis) as a Model of Aging and Age-Related Memory Impairment: An Overview

“…Furthermore, since the removal of LLs resulted in an increased rate of body growth at a cost of reduced female reproductive output, this finding suggests the existence of trade-offs between reproduction and nervous system function (98). Interestingly, ageing was also shown to affect mating strategy and sex role decision in L. stagnalis (16,99).…”

“…Finally, there is a growing literature that links the somatotropic systems to cognition and other brain functions in both vertebrates and invertebrates (94)(95)(96)(97). A recent study on L. stagnalis supports this notion as the surgical removal of lateral lobes (LLs; small accessory ganglia controlling the animals somatotropic/gonadotropic balance) enhanced appetitive LTM formation suggesting the existence of a connection between learning and memory performance, somatotropic control, and neuroendocrinology in L. stagnalis (98).…”

Transcriptome analysis provides genome annotation and expression profiles in the central nervous system ofLymnaea stagnalisat different ages

“…Studies have also focused on high cognitive behaviours, including learning and memory (Dodd, Rothwell, & Lukowiak, 2018;Sunada et al, 2017;Swinton et al, 2019;Tan & Lukowiak, 2018), as well as deciphering cellular mechanisms of synapse formation and synaptic plasticity during development (Getz, Wijdenes, Riaz, & Syed, 2018;Mersman, Jolly, Lin, & Xu, 2020;Onizuka et al, 2012). L. stagnalis has also recently gained increasing popularity for the investigation of brain aging and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease (Arundell et al, 2006;de Weerd, Hermann, & Wildering, 2017;Ford, Crossley, Vadukul, Kemenes, & Serpell, 2017;Hermann, Perry, Hamad, & Wildering, 2020;Maasz et al, 2017). It is important to note that comparative studies have highlighted several human homologs involved in aging and neurodegenerative disease in both A. californica and L. stagnalis (Fodor, Urban, Kemenes, Koene, & Pirger, 2020;Moroz et al, 2006;Moroz & Kohn, 2010), showing the great potential for future molecular insights into brain aging and pathology using these unique mollusc models.…”

Aging and disease-relevant gene products in the neuronal transcriptome of the great pond snail (Lymnaea stagnalis): a potential model of aging, age-related memory loss, and neurodegenerative diseases

“…This can be attributed to the presented benefits of their CNS and the slower rate of gene evolution in molluscan lineage resulting the presence of more gene homologs associated with human aging and (neurodegenerative) diseases in these species (Moroz 2009;Moroz et al 2006;Moroz and Kohn 2010;Walters and Moroz 2009). Although L. stagnalis has already been used successfully for modelling aging, Parkinson's and Alzheimer's diseases (Arundell et al 2006;de Weerd et al 2017;Ford et al 2017;Hermann et al 2007Hermann et al , 2020Maasz et al 2017;Patel et al 2006;Pirger et al 2014b;Scutt et al 2015;Vehovszky et al 2007;Yeoman and Faragher 2001;Yeoman et al 2008), due to the enormous set of publicly available transcriptome and genome data A. californica was the prevalent model of this field (Choi et al 2014;Moroz 2011;Moroz et al 2006;Moroz and Kohn 2010;Shemesh and Spira 2010a, b). For example, an earlier comparative analysis in A. californica yielded several homologs to human genes linked to aging and neurodegenerative/other diseases, opening the way for further and deeper investigations (Moroz et al 2006).…”