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Heatmap showing differences in relative expression changes of proinflammatory cytokines in brains of LPS-stimulated budgerigars and zebra finches. MeUnX = budgerigar, X = number of individual; TaGuY = zebra finch, Y = number of individual. The heatmap colour ranges from blue (lowest upregulation in expression) to red (highest upregulation in expression).
Source publication
In vertebrates, cannabinoids modulate neuroimmune interactions through two cannabinoid receptors (CNRs) conservatively expressed in the brain (CNR1, syn. CB1) and in the periphery (CNR2, syn. CB2). Our comparative genomic analysis indicates several evolutionary losses in the CNR2 gene that is involved in immune regulation. Notably, we show that the...
Contexts in source publication
Context 1
... IL6, IL17B and IL22 there was insufficient read representation to perform the statistical test and for IL15 we found no significant difference in gene expression between the two species ( p = 0.717). The results are shown in figure 3. To verify these transcriptomic patterns indicating functional effects of CNR2 loss on neuroimmune functioning in parrots, we followed the CNR1/2, IL1B and IL6 expression on messenger RNA (mRNA) level across the two taxa using RTqPCR. ...
Context 2
... IL6, IL17B and IL22 there was insufficient read representation to perform the statistical test and for IL15 we found no significant difference in gene expression between the two species ( p = 0.717). The results are shown in figure 3. To verify these transcriptomic patterns indicating functional effects of CNR2 loss on neuroimmune functioning in parrots, we followed the CNR1/2, IL1B and IL6 expression on messenger RNA (mRNA) level across the two taxa using RTqPCR. ...
Citations
... The immune system is remarkably flexible in terms of gene gain and loss (Chattopadhyay et al., 2020;Colgan et al., 2021;Divín et al., 2022;Krchlíková et al., 2023;Parham & Moffett, 2013;Solbakken et al., 2016;Velová et al., 2018). For example, gadiform fish have lost the MHC class II genes, a loss which seems to have been subsequently compensated for by an expansion of MHC class I gene copy number (Malmstrøm et al., 2016). ...
Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the diverse molecular mechanisms that shape immunity within and among species is still needed to gain insight into—and generate evolutionary hypotheses on—the ultimate drivers of immunological differences. Here, we discuss current advances in our understanding of molecular evolution underpinning jawed vertebrate immunity. First, we introduce the immunome concept, a framework for characterizing genes involved in immune defence from a comparative perspective, then we outline how immune genes of interest can be identified. Second, we focus on how different selection modes are observed acting across groups of immune genes and propose hypotheses to explain these differences. We then provide an overview of the approaches used so far to study the evolutionary heterogeneity of immune genes on macro and microevolutionary scales. Finally, we discuss some of the current evidence as to how specific pathogens affect the evolution of different groups of immune genes. This review results from the collective discussion on the current key challenges in evolutionary immunology conducted at the ESEB 2021 Online Satellite Symposium: Molecular evolution of the vertebrate immune system, from the lab to natural populations.
Abstract
Reviewing current advances in our understanding of molecular evolution underpinning vertebrate immunity, we propose hypotheses to explain differences in selection modes across immune genes and discuss supporting evidence.
... Whilst rarely studied, parrots represent an important group of widespread domestic animals with the potential to transmit microbial infections to humans (Jones et al. 2014;Balsamo et al. 2017;Nga et al. 2019). Compared to other birds, parrots may suffer from impaired regulation of inflammation (Divín et al. 2022), which could facilitate transmission of certain diseases. For example, pet parrots may be responsible for transmitting psittacosis, a bacterial infection caused by Chlamidia pssitaci (Balsamo et al. 2017;Ravichandran et al. 2021). ...
Digestive and respiratory tracts are inhabited by rich bacterial communities that can vary between their different segments. In comparison with other bird taxa with developed caeca, parrots that lack caeca have relatively lower variability in intestinal morphology. Here, based on 16S rRNA metabarcoding, we describe variation in microbiota across different parts of parrot digestive and respiratory tracts both at interspecies and intraspecies levels. In domesticated budgerigar (Melopsittacus undulatus), we describe the bacterial variation across eight selected sections of respiratory and digestive tracts, and three non-destructively collected sample types (faeces, and cloacal and oral swabs). Our results show important microbiota divergence between the upper and lower digestive tract, but similarities between respiratory tract and crop, and also between different intestinal segments. Faecal samples appear to provide a better proxy for intestinal microbiota composition than the cloacal swabs. Oral swabs had a similar bacterial composition as the crop and trachea. For a subset of tissues, we confirmed the same pattern also in six different parrot species. Finally, using the faeces and oral swabs in budgerigars, we revealed high oral, but low faecal microbiota stability during a 3-week period mimicking pre-experiment acclimation. Our findings provide a basis essential for microbiota-related experimental planning and result generalisation in non-poultry birds.
The endocannabinoid system (eCB) is a complex signaling network discovered in mammals during the
1980se1990s. It conventionally revolves around two arachidonic acid-derived mediators, N-arachidonoylethanolamine (anandamide) and 2-arachidonoyl-glycerol; their main receptors, the cannabinoid receptors of
type 1 (CB1) and type 2 (CB2), and the transient receptor potential vanilloid-1 channels; and the enzymes
responsible for their biosynthesis and degradation. However, drawing on these discoveries, numerous eCBlike signaling lipids beyond the classical eCBs, have been unveiled, together with their receptors and metabolic enzymes, thus forming a more complex signaling network known as the endocannabinoidome
(eCBome). This review explores the physiology, pharmacological complexity, and molecular targets of the
mammalian eCBome, highlighting its versatility and redundancy in the context of global health. Emerging
mediators, metabolic pathways and mechanisms, receptors, and their implications in human physiology and
pathology are described, particularly concerning metabolic disorders, pain, inflammation, neurodegenerative
diseases, and cancer. The importance of other “eCBomes” in nonmammalian forms of life that constitute the
external and internal environments of mammals is also discussed for the first time in this context. The
overarching objective of this article is to gain insights into the potential of eCBome-based therapeutic strategies aimed at enhancing both human and environmental well-being.
Since the discovery of the endocannabinoid system and due to the empirical evidence of the therapeutic effects on several illnesses both in humans and animals that follow the administration of exogenous cannabinoids (i.e., phytocannabinoids), numerous studies have been conducted. These investigations aimed to identify the expression and distribution of cannabinoid receptors in healthy and pathologic organs and tissues of different animal species and to define the interactions of phytocannabinoids with these receptors. In the last decade, pharmacokinetics, efficacy and tolerability of many Cannabis derivatives formulations, mainly containing cannabidiol, in the main species of veterinary interest, have been also investigated. This manuscript summarizes the findings reported by the scientific studies published so far on the molecular mode of action of the main phytocannabinoids, the localization of cannabinoid receptors in organs and tissues, as well as the pharmacokinetics, efficacy and tolerability of Cannabis derivatives in dogs, cats, horses and other species of veterinary interest. A deep knowledge of these issues is crucial for the use of phytocannabinoids for therapeutic purposes in animal species.
Objective:
To determine the pharmacokinetics of 8 cannabinoids and 5 metabolites after oral administration of single and multiple doses of a cannabidiol (CBD)-cannabidiolic acid (CBDA)-rich hemp extract to orange-winged Amazon parrots (Amazona amazonica) as well as to evaluate the extract's adverse effects.
Animals:
12 birds.
Procedures:
Based on pilot studies, a single-dose study based on 30/32.5 mg/kg of cannabidiol/cannabidiolic acid of a hemp extract was administered orally to 8 fasted parrots, and 10 blood samples were collected over 24 hours after administration. After a 4-week washout period, the hemp extract was administered orally to 7 birds at the previous dose every 12 hours for 7 days, and blood samples were collected at the previous time points. Cannabidiol, Δ9-tetrahydrocannabinol, cannabinol, cannabichromene, cannabigerol, cannabidiolic acid, cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, and 5 specific metabolites were measured by liquid chromatography-tandem/mass-spectrometry, and pharmacokinetic parameters were calculated. Adverse effects and changes in the plasma biochemistry and lipid panels were evaluated.
Results:
Pharmacokinetic parameters for cannabidiol, cannabidiolic acid, Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabinolic acid, and the metabolite 11-hydroxy-9-tetrahydrocannabinol were established. For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively. No adverse effects were detected during the multidose study. The predominant metabolite was 11-hydroxy-9-tetrahydrocannabinol.
Clinical relevance:
Twice daily oral administration of the hemp extract based on 30 mg/kg/32.5 mg/kg of cannabidiol/cannabidiolic acid was well tolerated and maintained plasma concentrations considered to be therapeutic in dogs with osteoarthritis. Findings suggest different cannabinoid metabolism from mammals.
