Abstract Freshwater snails of the genusBiomphalariaserve as intermediate hosts for the digenetic trematodeSchistosoma mansoni, the etiological agent for the most widespread form of intestinal schistosomiasis. As neuropeptide signaling in host snails can be altered by trematode infection, a neural transcriptomics approach was undertaken to identify peptide precursors inBiomphalaria glabrata, the major intermediate host forS.mansoniin the Western Hemisphere. Three transcripts that encode peptides belonging to the FMRF‐NH2‐related peptide (FaRP) family were identified inB.glabrata. One transcript encoded a precursor polypeptide (Bgl‐FaRP1; 292 amino acids) that included eight copies of the tetrapeptide FMRF‐NH2and single copies of FIRF‐NH2, FLRF‐NH2, and pQFYRI‐NH2. The second transcript encoded a precursor (Bgl‐FaRP2;347amino acids) that comprised 14 copies of the heptapeptide GDPFLRF‐NH2and 1 copy of SKPYMRF‐NH2. The precursor encoded by the third transcript (Bgl‐FaRP3; 287 amino acids) recapitulatedBgl‐FaRP2but lacked the full SKPYMRF‐NH2peptide. The three precursors shared a common signal peptide, suggesting a genomic organization described previously in gastropods. Immunohistochemical studies were performed on the nervous systems ofB.glabrataandB.alexandrina, a major intermediate host forS.mansoniin Egypt. FMRF‐NH2‐like immunoreactive (FMRF‐NH2‐li) neurons were located in regions of the central nervous system associated with reproduction, feeding, and cardiorespiration. Antisera raised against non‐FMRF‐NH2peptides present in the tetrapeptide and heptapeptide precursors labeled independent subsets of the FMRF‐NH2‐li neurons. This study supports the participation of FMRF‐NH2‐related neuropeptides in the regulation of vital physiological and behavioral systems that are altered by parasitism inBiomphalaria.
more »
« less
This content will become publicly available on January 18, 2026
Localization of Cholecystokinin/Sulfakinin Neuropeptides in Biomphalaria glabrata , an Intermediate Host for Schistosomiasis
ABSTRACT Snails belonging to the genusBiomphalariaserve as obligatory intermediate hosts for the trematodeSchistosoma mansoni, the causative agent for the most widespread form of schistosomiasis. The simpler nervous systems of gastropod molluscs, such asBiomphalaria, provide advantageous models for investigating neural responses to infection at the cellular and network levels. The present study examined neuropeptides related to cholecystokinin (CCK), a major multifunctional regulator of central nervous system (CNS) function in mammals. A neural transcriptome generated from the CNS ofBiomphalaria alexandrinaincluded a transcript encoding two CCK‐related peptides, designatedBalex‐CCK1 (pEGEWSYDY(SO3H)GLGGGRF‐NH2) andBalex‐CCK2 (NYGDY(SO3H)GIGGGRF‐NH2). Peptide expression was examined inBiomphalaria glabrataat the mRNA level using the hybridization chain reaction (HCR) protocol and at the protein level using an antibody againstBalex‐CCK1. Expression was detected in 60–70 neurons distributed throughout the CNS, as well as in profuse fiber systems connecting the ganglia and projecting to the periphery. CCK‐like immunoreactive (CCKli) fibers were also observed on organs associated with the cardiorespiratory (nephridium, mantle, gill) and male reproductive systems. A comparison of mRNA and peptide localization suggested that CCK expression could be regulated at the level of translation. A potential role of these peptides in mediating responses to infection by larval schistosomes is discussed.
more »
« less
- Award ID(s):
- 2217657
- PAR ID:
- 10568806
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Comparative Neurology
- Volume:
- 533
- Issue:
- 1
- ISSN:
- 0021-9967
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Cwiklinski, Krystyna (Ed.)The neglected tropical disease schistosomiasis impacts over 700 million people globally. Schistosoma mansoni , the trematode parasite that causes the most common type of schistosomiasis, requires planorbid pond snails of the genus Biomphalaria to support its larval development and transformation to the cercarial form that can infect humans. A greater understanding of neural signaling systems that are specific to the Biomphalaria intermediate host could lead to novel strategies for parasite or snail control. This study examined a Biomphalaria glabrata neural channel that is gated by the neuropeptide FMRF-NH 2 . The Biomphalaria glabrata FMRF-NH 2 gated sodium channel ( Bgl- FaNaC) amino acid sequence was highly conserved with FaNaCs found in related gastropods, especially the planorbid Planorbella trivolvis (91% sequence identity). In common with the P . trivolvis FaNaC, the B . glabrata channel exhibited a low affinity (EC 50 : 3 x 10 −4 M) and high specificity for the FMRF-NH 2 agonist. Its expression in the central nervous system, detected with immunohistochemistry and in situ hybridization, was widespread, with the protein localized mainly to neuronal fibers and the mRNA confined to cell bodies. Colocalization of the Bgl- FaNaC message with its FMRF-NH 2 agonist precursor occurred in some neurons associated with male mating behavior. At the mRNA level, Bgl- FaNaC expression was decreased at 20 and 35 days post infection (dpi) by S . mansoni . Increased expression of the transcript encoding the FMRF-NH 2 agonist at 35 dpi was proposed to reflect a compensatory response to decreased receptor levels. Altered FMRF-NH 2 signaling could be vital for parasite proliferation in its intermediate host and may therefore present innovative opportunities for snail control.more » « less
-
Abstract Neuropeptide Y (NPY) is an evolutionarily conserved neurosecretory molecule implicated in a diverse complement of functions across taxa and in regulating feeding behavior and reproductive maturation inOctopus. However, little is known about the precise molecular circuitry of NPY‐mediated behaviors and physiological processes, which likely involve a complex interaction of multiple signal molecules in specific brain regions. Here, we examined the expression of NPY throughout theOctopuscentral nervous system. The sequence analysis ofOctopusNPY precursor confirmed the presence of both, signal peptide and putative active peptides, which are highly conserved across bilaterians.In situhybridization revealed distinct expression of NPY in specialized compartments, including potential “integration centers,” where visual, tactile, and other behavioral circuitries converge. These centers integrating separate circuits may maintain and modulate learning and memory or other behaviors not yet attributed to NPY‐dependent modulation inOctopus. Extrasomatic localization of NPY mRNA in the neurites of specific neuron populations in the brain suggests a potential demand for immediate translation at synapses and a crucial temporal role for NPY in these cell populations. We also documented the presence of NPY mRNA in a small cell population in the olfactory lobe, which is a component of theOctopusfeeding and reproductive control centers. However, the molecular mapping of NPY expression only partially overlapped with that produced by immunohistochemistry in previous studies. Our study provides a precise molecular map of NPY mRNA expression that can be used to design and test future hypotheses about molecular signaling in variousOctopusbehaviors.more » « less
-
Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self‐assemble intoβ‐sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self‐assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac‐(XKXE)2‐NH2peptides (X = hydrophobic residue). A series of Ac‐(XKXE)2‐NH2peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1‐naphthylalanine [1‐Nal], 2‐naphthylalanine [2‐Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self‐assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac‐X1KFEFKFE‐NH2and Ac‐(X1,5KFE)‐NH2peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT‐IR) spectroscopy indicatedβ‐sheet formation for all variants. Self‐assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self‐assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac‐(XKXE)2‐NH2peptides correlates to self‐assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self‐assembled amphipathic peptides as functional biomaterials.more » « less
-
Abstract Recent years have led to increased effort to describe and understand the peripheral nervous system and its influence on central mechanisms and behavior in gastropod molluscs. This study revealed that an antibody raised against keyhole limpet hemocyanin (KLH) cross‐reacts with an antigen(s) found extensively in both the central and the peripheral nervous systems ofBiomphalaria alexandrina. The results revealed KLH‐like immunoreactive (LIR) neurons in the cerebral, pedal, buccal, left pleural, right parietal, and visceral ganglion within the CNS with fibers projecting throughout all the peripheral nerves. Numerous KLH‐LIR peripheral sensory neurons located in the foot, lips, tentacles, mantle, esophagus, and penis exhibited a bipolar morphology with long tortuous dendrites. KLH‐LIR cells were also present in the eye and statocyst, thus suggesting the labeling of multiple sensory modalities/cell types. KLH‐LIR cells did not co‐localize with tyrosine hydroxylase (TH)‐LIR cells, which have previously been described in this and other gastropods. The results thus provide descriptions of thousands of peripheral sensory neurons, not previously described in detail. Future research should seek to pair sensory modalities with peripheral cell type and attempt to further elucidate the nature of KLH‐like reactivity. These findings also emphasize the need for caution when analyzing results obtained through use of antibodies raised against haptens conjugated to carrier proteins, suggesting the need for stringent controls to help limit potential confounds caused by cross‐reactivity. In addition, this study is the first to describe neuronal cross‐reactivity with KLH inBiomphalaria, which could provide a substrate for host‐parasite interactions with a parasitic trematode,Schistosoma.more » « less
An official website of the United States government
