biology Review Neurotoxicity in Marine Invertebrates: An Update Irene Deidda , Roberta Russo , Rosa Bonaventura , Caterina Costa , Francesca Zito † and Nadia Lampiasi *,† Istituto per la Ricerca e l’Innovazione Biomedica IRIB, Consiglio Nazionale delle Ricerche, Via Ugo La Malfa 153, 90146 Palermo, Italy; [email protected] (I.D.); [email protected] (R.R.); [email protected] (R.B.); [email protected] (C.C.); [email protected] (F.Z.) * Correspondence: [email protected]; Tel.: +39-0916809513 † These authors contributed equally. Simple Summary: The pollution of air, soil, and sea has grown in recent decades at the same pace as human development. Climate changes add further damage to the ecosystems. Nowadays, pollutants that derive from the anthropization of the environment are indicated as “emerging pollutants”. Marine organisms, especially invertebrates, are used as model systems for ecotoxicological studies also regarding the nervous system, even if studies on pollutants’ neurotoxic effects are still few. A great leap forward in knowledge can come from integrated omics studies that bring together genomics, transcriptomics, proteomics, and metabolomics data. These studies have revealed that pollutants are dangerous for the life of marine organisms, and not only because they can be mod- ified in the environment, but also because they can combine giving rise to new mixtures. These new combinations can be even more harmful than individual pollutants. We must not forget that many marine organisms, both invertebrates and vertebrates, become part of the human food chain. Therefore, ultimately, the pollutants that contaminate the air, soil, and sea are potentially harmful to human health. The purpose of this review is to focus on some of the pollutants that are most frequently present in marine environments and analyze their neurotoxic potential effects on some marine model organisms. Citation: Deidda, I.; Russo, R.; Bonaventura, R.; Costa, C.; Zito, F.; Lampiasi, N. Neurotoxicity in Marine Abstract: Invertebrates represent about 95% of existing species, and most of them belong to aquatic Invertebrates: An Update. Biology ecosystems. Marine invertebrates are found at intermediate levels of the food chain and, therefore, 2021, 10, 161. https://doi.org/ they play a central role in the biodiversity of ecosystems. Furthermore, these organisms have a short 10.3390/biology10020161 life cycle, easy laboratory manipulation, and high sensitivity to marine pollution and, therefore, they are considered to be optimal bioindicators for assessing detrimental chemical agents that are re- Academic Editor: John R Turner lated to the marine environment and with potential toxicity to human health, including neurotoxicity. Received: 28 November 2020 In general, albeit simple, the nervous system of marine invertebrates is composed of neuronal and Accepted: 11 February 2021 glial cells, and it exhibits biochemical and functional similarities with the vertebrate nervous system, Published: 18 February 2021 including humans. In recent decades, new genetic and transcriptomic technologies have made the identification of many neural genes and transcription factors homologous to those in humans Publisher’s Note: MDPI stays neutral possible. Neuroinflammation, oxidative stress, and altered levels of neurotransmitters are some of with regard to jurisdictional claims in the aspects of neurotoxic effects that can also occur in marine invertebrate organisms. The purpose of published maps and institutional affil- this review is to provide an overview of major marine pollutants, such as heavy metals, pesticides, iations. and micro and nano-plastics, with a focus on their neurotoxic effects in marine invertebrate organisms. This review could be a stimulus to bio-research towards the use of invertebrate model systems other than traditional, ethically questionable, time-consuming, and highly expensive mammalian models. Copyright: © 2021 by the authors. Keywords: nervous system; echinoderms; molluscs; crustaceans; emerging contaminants; heavy Licensee MDPI, Basel, Switzerland. metals; pesticides; microplastics; omics This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Biology 2021, 10, 161. https://doi.org/10.3390/biology10020161 https://www.mdpi.com/journal/biology Biology 2021, 10, x FOR PEER REVIEW 2 of 28 Biology 2021, 10, 161 2 of 27 In the frame of the global environmental changes, rising and worrying data on both the environmental1. Introduction contamination and the related toxicology have been recorded since the mid-twentiethIn the century, frame of thewhen global the environmentalhuman activities changes, that are rising oriented and worrying towards dataindustrial on bothi- the zationenvironmental and globalization contamination began to and intensify. the related In particular, toxicology marine have been ecosystems recorded sinceexhibit the a mid- widetwentieth variety of century, hazardous when anthropogenic the human activitiespollutants that that are pervade oriented the towards entire water industrialization column, includingand globalization sediments, especially began to intensify. along the In coasts particular, that exhibit marine the ecosystems differentexhibit levels of a wide human variety activitiesof hazardous releasing anthropogenicindustrial, agricultural, pollutants hospitals, that pervade clinics the, and entire domestic water wastes column, into including the sea [1sediments,–3]. Without especially considering along the the biodegradable coasts that exhibit contaminants the different that levels arise of from human organic activities waste,releasing the main industrial, global concerns agricultural, are related hospitals, to the clinics, release and of emerging domestic contaminants wastes into the (ECs) sea [,1 –3]. also Withoutcalled micropollutants, considering the including, biodegradable among contaminants others, heavy that metals, arise microplastics, from organic waste,nano- the particles,main pharmaceuticals global concerns are, and related personal to the care release products of emerging (PPCPs) contaminants (drugs chemicals, (ECs), also etc.), called xenobioticsmicropollutants,, such as pesticides including, (insecticides, among others, herbicides heavy,metals, and fungicides) microplastics,, and endocrine nanoparticles, disruptingpharmaceuticals, compounds and (EDC) personal, etc. Due care to products their persistence (PPCPs) (drugs in the chemicals,environment, etc.), accumu- xenobiotics, lationsuch in the as pesticidesliving tissues (insecticides, via the food herbicides, chains, and and toxicity, fungicides), they endanger and endocrine the health disrupting of the marinecompounds biota (EDC),as well etc.as th Duee human to their health persistence [4–7]. The in the ECs environment, impact can accumulationdetermine sub in- the lethal,living acute tissues, or chronic via the effects food to chains, the single and organism toxicity, theylevel, endanger or can be extended the health to of the the pop- marine ulationbiota level, as well influencing as the human, in this health case, population [4–7]. TheECs dynamics, impact genetic can determine, and diversity sub-lethal, of the acute, ecosystemor chronic [2]. Through effects to the the impairment single organism of cellular level, orhomeostasis can be extended and gene to theexpression population reg- level, influencing, in this case, population dynamics, genetic, and diversity of the ecosystem [2]. ulation, the ECs can cause human disorders, as well as determine epigenetic phenomena Through the impairment of cellular homeostasis and gene expression regulation, the ECs altering gene functions with inherited effects [8]. Therefore, many ECs, even if in trace, can cause human disorders, as well as determine epigenetic phenomena altering gene can represent a high environmental risk factor, reached by trophic transfer animal species, functions with inherited effects [8]. Therefore, many ECs, even if in trace, can represent and cause several adverse effects in the human health, including alterations in the struc- a high environmental risk factor, reached by trophic transfer animal species, and cause ture and function of the nervous system (NS) and, thus, contribute to neurodevelopmental several adverse effects in the human health, including alterations in the structure and disorders (DNT) and neurological diseases. Most neurotoxic contaminants are highly lip- function of the nervous system (NS) and, thus, contribute to neurodevelopmental disorders ophilic and they easily cross the blood brain barrier (BBB) and the placenta [4] (Figure 1). (DNT) and neurological diseases. Most neurotoxic contaminants are highly lipophilic and they easily cross the blood brain barrier (BBB) and the placenta [4] (Figure1). Figure 1. Diagram describing a wide variety of hazardous anthropogenic pollutants that pervade the entire water column, including sediments, originating from different levels of human activities Figure 1. Diagram describing a wide variety of hazardous anthropogenic pollutants that pervade the entirereleasing water industrial, column, including agricultural, sediments, hospitals, originating clinics and from domestic different wasted levels into of thehuman sea, activities with potential releasingand adverseindustrial, effects agricultural, on human hospitals, health. clinics and domestic wasted into