Physiological Roles of Serotonin in Bivalves: Possible Interference by Environmental Chemicals Resulting in Neuroendocrine Disruption

Abstract

Contaminants of Emerging Concerns (CECs) are defined as chemicals not commonly monitored in aquatic ecosystems, but with the potential to cause adverse effects on biota. CECs include Endocrine Disrupting Chemicals (EDCs) and Neuro-Endocrine disruptors (NEDs) of vertebrates. However, most invertebrates only rely on neuroendocrine systems to maintain homeostatic processes. Although conserved neuroendocrine components have been characterized in ecologically relevant groups, limited knowledge on invertebrate neuroendocrinology makes it difficult to define EDCs and NEDs in most species. The monoamine serotonin (5-hydroxytryptamine, 5-HT) acts both as a neurotransmitter and as a peripheral hormone in mammals. In molluscs, 5-HT is involved in multiple physiological roles and molecular components of the serotonergic system have been identified. This review is focused on the effects of CECs on the serotonergic system of bivalve molluscs. Bivalves are widespread in all aquatic environments, estuarine and coastal areas in particular, where they are exposed to a variety of chemicals. In bivalves, 5-HT is involved in gametogenesis and spawning, oocyte maturation and sperm motility, regulates heart function, gill ciliary beating, mantle/siphon function, the ‘‘catch’’ state of smooth muscle and immune responses. Components of 5-HT transduction (receptors and signaling pathways) are being identified in several bivalve species. Different CECs have been shown to affect bivalve serotonergic system. This particularly applies to antidepressants, among the most commonly detected human pharmaceuticals in the aquatic environment. In particular, selective serotonin reuptake inhibitors (SSRIs) are frequently detected in seawater and in bivalve tissues. Information available on the effects and mechanisms of action of SSRIs on the serotonergic system of adult bivalves is summarized. Data are also reported on the effects of CECs on development of neuroendocrine pathways of early larval stages, in particular on the effects of model EDCs in the marine mussel Mytilus galloprovincialis. Overall, available data point at the serotonergic system as a sensitive target for neuroendocrine disruption in bivalves. The results contribute drawing Adverse Outcome Pathways (AOPs) for model EDCs and SSRIs in larvae and adults. However, basic research on neuroendocrine signaling is still needed to evaluate the potential impact of neuroendocrine disruptors in key invertebrate groups of aquatic ecosystems.

Role of the Neuroendocrine System of Marine Bivalves in Their Response to Hypoxia

“…5-HT regulates the contraction and relaxation of the adductor and the anterior byssus retractor muscle (ABRM), and is involved in the regulation of complex changes in the protective behavioral reactions of mollusks during hypoxia. In bivalves such as the blue mussel M. edulis , smooth muscles such as the ABRM can be locked in the contracted state (i.e., “catch”), a crucial function that keeps the shell valves firmly closed during periods of air exposure [ 122 , 123 ]. This occurs following the initial activation of the muscle.…”

“…Protein kinase A (PKA) is then responsible for the rapid muscle relaxation through the phosphorylation of twitchin, a myosin-binding protein [ 119 , 125 ]. The ABRM fibers in the catch state can be relaxed by serotonergic nerve stimulation or by the external application of 5-HT [ 123 , 125 , 127 , 128 , 129 ]. 5-HT induces an increase in the intracellular cyclic AMP (cAMP) concentration [ 130 ], which activates cAMP-dependent PKA to result in the phosphorylation of twitchin, a high-molecular-weight protein terminating the catch state [ 131 ].…”

Serotonin Receptors and Their Involvement in Melanization of Sensory Cells in Ciona intestinalis

“…In animals, 5-HT mediates several functions in the central and peripheral nervous systems too. Moreover, its involvement in chemotaxis and chemosignaling has been reported in unicellular organisms, and its diverse roles as an intracellular regulator of cell activity have been described in both vertebrates and invertebrates [ 2 , 3 , 4 ].…”

“…They are all expressed in the central nervous system (CNS) and various body districts, such as the gastrointestinal tract or cardiovascular system [ 10 , 11 ]. Homologs of 5HTRs are widely present in invertebrates from planarians [ 12 ] to mollusks [ 3 , 9 ] and insects [ 13 , 14 ]. Based on evolutionary studies, 5HTRs are among the oldest receptors of the rhodopsin-like family, as they appeared 700–750 million years ago, predating the invertebrate–vertebrate divergence estimated to have occurred about 600 million years ago [ 15 , 16 , 17 ].…”

Spatial Variation of Soft Shell Clam Biochemical Health Status-Impacts on Age Pigments, Glucose and Melatonin Status

“…Melatonin is synthetized from serotonin, which in turn, is produced from tryptophan, an essential amino acid usually produced from microbial and plant sources hence, acquired from feeding in clams. Melatonin is involved in gonad growth from the stimulation of gonadotropin-releasing hormone and serotonin is involved for gamete maturation and promotes spawning (Ding et al, 2021;Canesi et al, 2022). Hence, the balance between serotonin and melatonin changes during the day, follows a circadian cycle, where melatonin is associated with resting phase and gonad growth.…”