This paper describes the advantages of
adopting a molluscan model for studying the
biological basis of some central nervous system
pathologies affecting humans. In particular, I will
focus on the freshwater snail Lymnaea stagnalis,
which is already the subject of electrophysiological
studies related to learning and memory, as well as
ecotoxicological studie

F. Tascedda

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

477 ISJ 14: 477-479, 2017                                                       ISSN 1824-307X   LETTER TO EDITOR  Lymnaea stagnalis as model of neuropsychiatric disorders  F Tascedda  Department of Life Sciences and Center for Neuroscience and Neurotechnology University of Modena and Reggio Emilia, Modena, Italy      Accepted November 14, 2017  To the Editor This paper describes the advantages of adopting a molluscan model for studying the biological basis of some central nervous system pathologies affecting humans. In particular, I will focus on the freshwater snail Lymnaea stagnalis, which is already the subject of electrophysiological studies related to learning and memory, as well as ecotoxicological studies (Il-Han et al., 2010; Bavan et al., 2012; Ivashkin et al., 2015; Benatti et al., 2017; Ito et al., 2017). Understanding psychiatric and neurological disorders is a major medical and scientific challenge. These pathologies are extremely widespread and contribute in an important way to the high cost of public health (Nestler et al., 2010; Tascedda et al., 2015; Kaiser et al., 2015). Unfortunately, the developing or mature human brain are not open to direct molecular observation, and experimental manipulations are clearly not ethical. This makes it necessary and urgent to develop new and reliable animal models for the study of brain disorders. While the research community has accepted the value of rodent models for the study of human pathology and treatment, there is less awareness of the utility of other small vertebrate and invertebrate animal models. However, in recent years, the neuroscientists are increasingly turning to smaller, non-rodent models to understand molecular physiopathological mechanisms related to neurological or psychiatric disorders. Although they can never replace clinical research, these species offer flexible genetic tools that can be useful to validate the function of specific genes, or their role in more complex functions. Although, animal models, of any origin, size or complexity, can never summarize the full phenotype of a human clinical disorder, in particular neuropsychiatric ones, different small animals, such as, worms, flies, bees and fish offer new important and innovative tools for the neuroscientist. (Burne et al., 2011; Curran et al., 2012; Tascedda et al., 2015). ___________________________________________________________________________  Corresponding author: Fabio Tascedda Department of Life Sciences University of Modena and Reggio Emilia Via Campi 287, 41125 Modena, Italy E-mail: fabio.tascedda@unimore.it  Indeed, by using a range of models of different complexity, together with a number of different experimental approaches, researchers can divide complex phenotypes into simpler neurobiological correlates of clinical syndromes (Nestler et al., 2010). As mentioned above, normally, for these studies, rats and mice have been used (Vinet et al., 2003; Vinet et al., 2004; Blom et al., 2006; Alboni et al., 2011; Benatti et al., 2011), but this approach may not be always effective and is accompanied by many ethical and economical problems (Tascedda et al., 2015). Many researchers have attempted to solve the problem by using in vitro cell systems (Alboni et al.; 2013, 2014; Caraci et al., 2016) that have many important advantages (Tascedda et al., 2015). Unfortunately, the results are often inconclusive and fail to elucidate the basis of disease (Alberts, 2010). Given of these considerations, the need to identify alternative and reliable models that have fewer ethical restrictions is both important and urgent. Invertebrates, thanks to their relatively simple nervous system structure are fast becoming a useful tool for the study of neuronal physiology and for better disease process characterization (Kaang et al., 1993; Ottaviani et al., 2013; Tascedda et al., 2015).  Above all, molluscan gastropods, such as Aplysia, Hermissenda, Limax, and so forth, have been widely recognized as useful animals with which to study the molecular and cellular mechanisms underlying complex human pathologies such as neurological and psychiatric disorders (Kandel et al., 1965; Gelperin 1975; Nestler et al., 2010; Burne et al., 2011).  Furthermore, numerous studies suggest that the pond snail L. stagnalis could be an innovative useful model in genetic and translational research for the study of the molecular basis of human brain diseases and for the development of new therapeutic strategies (Tascedda et al., 2015, Ito et al., 2017, Benatti et al., 2017). L. stagnalis, an aquatic pulmonate gastropod with a central nervous system (CNS) consisting of ≈20,000 neurons organized in a ring of interconnected ganglia, has proven to be an extremely interesting and accessible model to study 478 fundamental aspects of CNS function such as synaptic plasticity and associative memory (Sadamoto et al., 2004, 2010; Ito et al., 2017). Compared to D. melanogaster and C. elegans, Lymnaea has many benefits due to the large size of its neurons, results from electrophysiological studies, and its already characterized neuronal circuit (Andrianov et al., 2015). Lymnaea also offers the possibility of performing behavioral tests [Ito et al., 2017]. More importantly, while D. melanogaster and C. elegans have a life cycle of 2 - 3 weeks, Lymnaea has an average life span of 9 - 12 months. This last factor becomes particularly interesting and useful in studies on chronic human pathologies, especially neurodegenerative diseases such as Alzheimer's, Parkinson's or chronic psychiatric diseases such as major depression, schizophrenia or bipolar disorder. In this context, L. stagnalis offers, to the neuroscientist involved in translational medicine, a powerful new tool to study neuropsychiatric diseases and allow the identification of new molecular targets for the development of innovative therapeutic strategies. Using an interdisciplinary approach, studying the appropriate animal model, passing from the more simple ones to the most complex, while combining different methods and expertise that include fields as evolution, ecology, and life history theory with physiology, pathology, neuroscience, genetics, molecular biology, and ultimately behaviour it will be possible to open new frontiers to understand and cure brain illnesses.  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Lymnaea stagnalis as model of neuropsychiatric disorders

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