Animal Inflammation-Based Models of Neuropsychiatric Disorders.

Mounting evidence links psychiatric disorders to central and systemic inflammation. Experimental (animal) models of psychiatric disorders are important tools for translational biopsychiatry research and CNS drug discovery. Current experimental models, most typically involving rodents, continue to reveal shared fundamental pathological pathways and biomarkers underlying the pathogenetic link between brain illnesses and neuroinflammation. Recent data also show that various proinflammatory factors can alter brain neurochemistry, modulating the levels of neurohormones and neurotrophins in neurons and microglia. The role of "active" glia in releasing a wide range of proinflammatory cytokines also implicates glial cells in various psychiatric disorders. Here, we discuss recent animal inflammation-related models of psychiatric disorders, focusing on their translational perspectives and the use of some novel promising model organisms (zebrafish), to better understand the evolutionally conservative role of inflammation in neuropsychiatric conditions.

Current State of Modeling Human Psychiatric Disorders Using Zebrafish.

Psychiatric disorders are highly prevalent brain pathologies that represent an urgent, unmet biomedical problem. Since reliable clinical diagnoses are essential for the treatment of psychiatric disorders, their animal models with robust, relevant behavioral and physiological endpoints become necessary. Zebrafish (Danio rerio) display well-defined, complex behaviors in major neurobehavioral domains which are evolutionarily conserved and strikingly parallel to those seen in rodents and humans. Although zebrafish are increasingly often used to model psychiatric disorders, there are also multiple challenges with such models as well. The field may therefore benefit from a balanced, disease-oriented discussion that considers the clinical prevalence, the pathological complexity, and societal importance of the disorders in question, and the extent of its detalization in zebrafish central nervous system (CNS) studies. Here, we critically discuss the use of zebrafish for modeling human psychiatric disorders in general, and highlight the topics for further in-depth consideration, in order to foster and (re)focus translational biological neuroscience research utilizing zebrafish. Recent developments in molecular biology research utilizing this model species have also been summarized here, collectively calling for a wider use of zebrafish in translational CNS disease modeling.

New approaches concerning the testis of Astyanax lacustris (Characidae): immunohistochemical studies.

Astyanax lacustris, locally known as lambari-do-rabo-amarelo, is a study model for Neotropical fish. Testis of A. lacustris shows deep morphophysiological changes throughout the annual reproductive cycle. This work analyzed the distribution of claudin-1, actin, and cytokeratin as elements of the cytoskeleton in germinal epithelium and interstitium; the distribution of type I collagen, fibronectin, and laminin as extracellular matrix compounds; and the localization of androgen receptor in the testis of this species. Claudin-1, cytokeratin, and actin were present in the Sertoli cells and modified Sertoli cells, and actin was also detected in peritubular myoid cells. Type I collagen were in the interstitial tissue, laminin in the basement membrane of germinal epithelium and endothelium, but fibronectin was additionally detected in the germinal epithelium compartment. The labeling of androgen receptor was higher in peritubular myoid cells and undifferentiated spermatogonia, and weaker labeling was detected in type B spermatogonia. Therefore, the present work highlights new aspects of the biology of the testis of A. lacustris, and contribute to amplify the understanding of this organ.

Towards Modeling Anhedonia and Its Treatment in Zebrafish.

Mood disorders, especially depression, are a major cause of human disability. The loss of pleasure (anhedonia) is a common, severely debilitating symptom of clinical depression. Experimental animal models are widely used to better understand depression pathogenesis and to develop novel antidepressant therapies. In rodents, various experimental models of anhedonia have already been developed and extensively validated. Complementing rodent studies, the zebrafish (Danio rerio) is emerging as a powerful model organism to assess pathobiological mechanisms of affective disorders, including depression. Here, we critically discuss the potential of zebrafish for modeling anhedonia and studying its molecular mechanisms and translational implications.

Induction of aggression and anxiety-like responses by perfluorooctanoic acid is accompanied by modulation of cholinergic- and purinergic signaling-related parameters in adult zebrafish.

Perfluorooctanoic acid (PFOA) is a contaminant of global concern owing to its prevalent occurrence in aquatic and terrestrial environments with potential hazardous impact on living organisms. Here, we investigated the influence of realistic environmental concentrations of PFOA (0, 0.25, 0.5, or 1.0 mg/L) on relevant behaviors of adult zebrafish (Danio rerio) (e.g., exploration to novelty, social preference, and aggression) and the possible role of PFOA in modulating cholinergic and purinergic signaling in the brain after exposure for 7 consecutive days. PFOA significantly increased geotaxis as well as reduced vertical exploration (a behavioral endpoint for anxiety), and increased the frequency and duration of aggressive episodes without affecting their social preference. Exposure to PFOA did not affect ADP hydrolysis, whereas ATP and AMP hydrolysis were significantly increased at the highest concentration tested. However, AChE activity was markedly decreased in all PFOA-exposed groups when compared with control. In conclusion, PFOA induces aggression and anxiety-like behavior in adult zebrafish and modulates both cholinergic and purinergic signaling biomarkers. These novel data can provide valuable insights into possible health threats related to human activities, demonstrating the utility of adult zebrafish to elucidate how PFOA affects neurobehavioral responses in aquatic organisms.

Chemical characterisation by UPLC-Q-ToF-MS/MS and antibacterial potential of Coffea arabica L. leaves: A coffee by-product.

INTRODUCTION: Coffea arabica L. leaves are considered a by-product of the coffee industry however they are sources of several bioactive compounds. OBJECTIVES: This study aimed to evaluate the chemical composition and the in vitro antibacterial activity of the lyophilised ethanol extract of arabica coffee leaves (EE-CaL). MATERIAL AND METHODS: The chemical characterisation of EE-CaL was performed using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-ToF-MS/MS). The in vitro antibacterial effect of EE-CaL was evaluated using the broth microdilution method and the adapted drop plate agar method to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), respectively. RESULTS: The chemical analysis of EE-CaL revealed the presence of compounds from the alkaloid class, such as trigonelline and caffeine, in addition to the phenolic compounds such as quinic acid, 5-caffeoylquinic acid, caffeic acid-O-hexoside, mangiferin, (epi)catechin, (epi)catechin monoglucoside and procyanidin trimer. Regarding the antibacterial potential, EE-CaL was active against Gram-positive and Gram-negative bacteria, being more effective against Escherichia coli (ATCC 25922) (MIC = 2500 µg/mL and bactericidal effect). CONCLUSION: The results of this research suggest that coffee leaves, a by-product, possess compounds with antibacterial properties. Thus, further studies with coffee leaf extracts must be carried out to relate the compounds present in the extract with the antibacterial activity and find the mechanisms of action of this extract against bacteria.

Towards Zebrafish Models of CNS Channelopathies.

Channelopathies are a large group of systemic disorders whose pathogenesis is associated with dysfunctional ion channels. Aberrant transmembrane transport of K+, Na+, Ca2+ and Cl- by these channels in the brain induces central nervous system (CNS) channelopathies, most commonly including epilepsy, but also migraine, as well as various movement and psychiatric disorders. Animal models are a useful tool for studying pathogenesis of a wide range of brain disorders, including channelopathies. Complementing multiple well-established rodent models, the zebrafish (Danio rerio) has become a popular translational model organism for neurobiology, psychopharmacology and toxicology research, and for probing mechanisms underlying CNS pathogenesis. Here, we discuss current prospects and challenges of developing genetic, pharmacological and other experimental models of major CNS channelopathies based on zebrafish.

Molecular characterization of different preproGnRHs in Astyanax altiparanae (Characiformes): Effects of GnRH on female reproduction.

Gonadotropin-releasing hormone (GnRH) is a key molecule in the initiation of the hypothalamic-pituitary-gonadal axis. Thus, knowledge about GnRH may contribute to the effectiveness of species reproduction. Using a Neotropical tetra Astyanax altiparanae as a fish model species, the GnRH forms were characterized at the molecular level and the role of injected GnRHs in vivo was evaluated. The full-length complementary DNA (cDNA) sequences of preproGnRH2 (612 bp) and preproGnRH3 (407 bp) of A. altiparanae were obtained, and the GnRH1 form was not detected. The cDNA sequences of preproGnRH2 and preproGnRH3 were found to be conserved, but a change in the amino acid at position 8 of the GnRH3 decapeptide of A. altiparanae was observed. All the injected GnRHs stimulated lhß messenger RNA (mRNA) expression but not fshß mRNA expression, and only GnRH2 was able to increase maturation-inducing steroid (MIS) levels and possibly stimulate oocyte release. Furthermore, only GnRH2 was able to start the entire reproductive hormonal cascade and induce spawning.

TOMOGRAPHIC ATTENUATION OF THE HEPATIC PARENCHYMA OF ADULT FREE-RANGING AND CAPTIVE BOAS (BOA CONSTRICTOR).

Improperly managed care conditions for reptiles can lead to clinical problems, including those of nutritional origin. A diagnostic tool to aid in the assessment of hepatic lipidosis is warranted. Evaluation of attenuation using quantitative computed tomography has a variety of indications in animals and permits the standardization of hepatic computed tomography (CT) reference values, aiding in the diagnosis of lipidosis. The objective of this paper was to estimate hepatic quantitative CT reference values for boas because of the lack of data in the literature for this species. CT scans were performed in 13 boas (Boa constrictor constrictor): 5 under managed care and 8 that were free ranging. Results show that the mean hepatic attenuation in the captive boa group was well below the mean for the free-ranging animals (P < 0.05) with respective values of 48.78 ± 6.57 and 61.76 ± 7.11 HU. These results suggest an influence of managed care on liver attenuation. These results were observed despite the lack of clinical or laboratory changes. This imaging technique is useful to detect early hepatic changes; however, clinical relevance is unknown at this point. Further studies and standardization of species-specific values for hepatic quantitative CT would contribute to better understanding of the physiologic, physiopathologic, environmental, and nutritional processes.

Determination of baseline values for routine ophthalmic tests in bearded capuchin (Sapajus libidinosus).

BACKGROUND: Establish baseline values for ophthalmic diagnostic tests in Sapajus libidinosus. METHODS: Ophthalmic diagnostic tests, namely Schirmer tear test 1 (STT-1), intraocular pressure (IOP), B-mode ultrasound, culture of the bacterial conjunctival microbiota, and conjunctival exfoliative cytology, were performed in 15 S. libidinosus. RESULTS: Mean values found were as follows: 2.50 ± 2.94 mm/min for the STT-1; 13.3 ± 3.32 mm Hg for the IOP; 2.47 ± 0.41 mm for the depth of the anterior chamber; 2.86 ± 0.96 mm for the axial length of the lens; 10.97 ± 0.48 mm for the depth of the vitreous chamber; and 16.32 ± 1.24 mm for the axial length of the eyeball. The bacterial genus most frequently found was Staphylococcus spp. Conjunctival cytology showed intermediate epithelial, squamous superficial epithelial, and keratinized cells. CONCLUSIONS: Determination of baseline values for eye measurements and ophthalmic tests will assist in the diagnosis of eye diseases in S. libidinosus monkeys.

OSTEODENSITOMETRY AND TOMOGRAPHIC FINDINGS IN FOUR CAPTIVE GIANT SOUTH AMERICAN TURTLES (PODOCNEMIS EXPANSA) WITH METABOLIC BONE DISEASE.

Giant South American turtles (Podocnemis expansa) are at a risk of extinction because of the rapid decline in their population over the last few decades. Metabolic bone disease (MBD) is common in captive testudines, but is often not diagnosed until a later stage. The authors present the cases of four captive giant South American turtles with carapace deformity secondary to MBD that underwent computed tomography (CT) scans of the carapace bones and vertebral column. Findings indicative of changes in geometry were found in both. The cancellous bone pattern was characterized by varying degrees of increased trabecular spacing and cortical thinning of the pleural bones. Bone densitometry analysis of the pleural and neural bones and at the level of the body of the third, fourth, and fifth dorsal vertebrae showed mean density values much lower than those found in two adult specimens of the same species that were considered healthy. In conclusion, CT contributed important information on the degree of demineralization and possible structural changes due to MBD and should be considered a relevant tool for diagnosis of this condition.

QUANTITATIVE COMPUTED TOMOGRAPHY OF HEALTHY ADULT BOAS ( BOA CONSTRICTOR).

The evaluation of radiodensity using quantitative computed tomography (QCT) has several indications in animals. It allows for standardization of reference values for bone densitometry and helps in the clinical diagnosis of diseases. Currently, there is a lack of such data in the literature for Boa constrictor constrictor. Therefore, the objective of this study was to estimate reference values for bone density in boas ( Boa constrictor constrictor). Computed tomography scans were performed on 10 adult, healthy, free-ranging boas. Results showed mean values of vertebral trabecular bone for free-ranging boas were 1,237.91 ± 54.61 mg/cm3. Because of the difficulty in obtaining clinical and radiographic diagnoses of metabolic bone diseases, especially in a timely manner, densitometry may become a helpful tool in preventive veterinary medicine.

USE OF COMPUTED TOMOGRAPHY FOR INVESTIGATION OF HEPATIC LIPIDOSIS IN CAPTIVE CHELONOIDIS CARBONARIA (SPIX, 1824).

Computed tomography is a sensitive and highly applicable technique for determining the degree of radiographic attenuation of the hepatic parenchyma. Radiodensity measurements of the liver can help in the diagnosis of hepatic lipidosis in humans and animals. The objective was to investigate the presence of hepatic lipidosis in captive red-footed tortoises (Chelonoidis carbonaria) using computed tomography. Computed tomography was performed in 10 male red-footed tortoises. Mean radiographic attenuation values for the hepatic parenchyma were 11.2±3.0 Hounsfield units (HU). Seven red-footed tortoises had values lower than 20 HU, which is compatible with C. carbonaria hepatic lipidosis. These results allowed an early diagnosis of the hepatic changes and suggested corrective measures regarding feeding and management protocols.

Morphologic study of the liver of lambari (Astyanax altiparanae) with emphasis on the distribution of cytokeratin.

Studies on the morphology of the liver of teleosts reflect some controversy in the interpretation of the data, but also provide confirmation of variations in the structure of the organ in several species. Thus, we intend to understand the specific structural organization of the liver of Astyanax altiparanae. Specimens were collected in the city of Andirá, Paraná, Brazil. The livers were processed according to histological routine for inclusion in Paraplast, and the sections were stained with HE and Mallory's trichrome or followed the protocol for fluorescence immunohistochemistry, anti-cytokeratin. The liver of A. altiparanae was covered by a capsule of connective tissue, without delimiting lobes. The hepatocytes had an arrangement in cords around sinusoids. Melanomacrophage centers were observed. The vascular components and intrahepatic pancreatic acini were distributed between hepatocytes. Presence of cytokeratin was detected in tissues that lined the liver and endothelial cells of sinusoids. The comparison of the liver of A. altiparanae to other characids corroborates with the fact that there is variation in the morphology of the liver even between closely related species. Moreover, it appears that in this species, endothelial cells of sinusoids can synthesize the cytokeratin filaments required for the regulation of blood flow in capillaries in adults.

Pituitary gland morphogenesis and ontogeny of adenohypophyseal cells of Salminus brasiliensis (Teleostei, Characiformes).

In this study, we describe for the first time the details of the pituitary gland morphogenesis and the ontogeny of adenohypophyseal cells of a South American Characiform species with great importance for Brazilian Aquaculture, Salminus brasiliensis (Characiformes, Characidae), from hatching to 25 days after hatching (dah), by histochemical and immunocytochemical methods. The pituitary placode was first detected at hatching (0 dah), and the pituitary anlage became more defined at 0.5 dah. The neurohypophysis (NH) development started at 3 dah, and the early formation of its stalk at 12.5 dah. An increase in adenohypophyseal and NH tissues was also observed, and in juveniles at 25 dah, the pituitary displayed similar morphology to that found in adults of this species, displaying the main features of the teleost pituitary. PRL cells were detected at 0.5 dah, together with ACTH and α-MSH cells, followed by GH and SL cells at 1.5 dah. ß-FSH cells were detected at 25 dah, while ß-LH cells at 5 dah. The pituitary development in this species comprises a dynamic process similar to other teleosts. Our findings in S. brasiliensis corroborate the heterogeneity in the ontogeny of adenohypophyseal cells in teleosts and suggest a role for adenohypophyseal hormones in the early development of this species.

Zebrafish models for studying cognitive enhancers.

Cognitive decline is commonly seen both in normal aging and in neurodegenerative and neuropsychiatric diseases. Various experimental animal models represent a valuable tool to study brain cognitive processes and their deficits. Equally important is the search for novel drugs to treat cognitive deficits and improve cognitions. Complementing rodent and clinical findings, studies utilizing zebrafish (Danio rerio) are rapidly gaining popularity in translational cognitive research and neuroactive drug screening. Here, we discuss the value of zebrafish models and assays for screening nootropic (cognitive enhancer) drugs and the discovery of novel nootropics. We also discuss the existing challenges, and outline future directions of research in this field.

Can we gain translational insights into the functional roles of cerebral cortex from acortical rodent and naturally acortical zebrafish models?

Cerebral cortex is found only in mammals and is particularly prominent and developed in humans. Various rodent models with fully or partially ablated cortex are commonly used to probe the role of cortex in brain functions and its multiple subcortical projections, including pallium, thalamus and the limbic system. Various rodent models are traditionally used to study the role of cortex in brain functions. A small teleost fish, the zebrafish (Danio rerio), has gained popularity in neuroscience research, and albeit (like other fishes) lacking cortex, its brain performs well some key functions (e.g., memory, consciousness and motivation) with complex, context-specific and well-defined behaviors. Can rodent and zebrafish models help generate insights into the role of cortex in brain functions, and dissect its cortex-specific (vs. non-cortical) functions? To address this conceptual question, here we evaluate brain functionality in intact vs. decorticated rodents and further compare it in the zebrafish, a naturally occurring acortical species. Overall, comparing cortical and acortical rodent models with naturally acortical zebrafish reveals both distinct and overlapping contributions of neocortex and 'precortical' zebrafish telencephalic regions to higher brain functions. Albeit morphologically different, mammalian neocortex and fish pallium may possess more functional similarities than it is presently recognized, calling for further integrative research utilizing both cortical and decorticated/acortical vertebrate model organisms.

Correction: Medeiros-Ventura et al. The Impact of Phytase and Different Levels of Supplemental Amino Acid Complexed Minerals in Diets of Older Laying Hens. Animals 2023, 13, 3709.

To allow the original publication to be better understood [...].

Complexed amino acid minerals vs. bis-glycinate chelated minerals: Impact on the performance of old laying hens.

The present study was to evaluate the effect of trace minerals (Zn, Mn, and Cu) from complexed amino acid minerals (ZMCAA) and bis-glycinate chelated minerals (ZMCGly) in laying hen diets on performance, internal and external egg quality, yolk mineral deposition, intestinal morphometry, and bone characteristics. From 78 to 98 weeks of age, 400 White LSL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per treatment. Treatments were distributed in a 2 × 2 factorial arrangement using either Zn, Mn, and Cu of ZMCAA or ZMCGly source at 2 levels: low (20, 20, and 3.5 mg/kg of Zn, Mn, and Cu, respectively) or high (40, 40, and 7 mg/kg of Zn, Mn, and Cu, respectively). The analysis of variance was performed, and in cases where differences were observed, the means were compared using Tukey's test (P < 0.05). The source and level of trace mineral supplementation had a significant impact on the performance of laying hens. Hens fed ZMCAA had higher egg production (P = 0.01), egg weight (P = 0.02), egg mass (P = 0.01), and lower feed conversion ratio (P = 0.05) compared to those fed ZMCGly. The ZMCAA supplementation showed higher albumen height (P = 0.01), albumen weight (P = 0.01), and eggshell thickness (P < 0.01). The deposition of Zn (P < 0.01), Mn (P < 0.01), and Cu (P < 0.01) in the egg yolk was greater for hens received ZMCAA. Tibia weight (P = 0.04) and bone densitometry (P < 0.01) in the tibia were higher with ZMCAA supplementation. In the small intestine, ZMCAA resulted in longer villi (P = 0.02) and shorter crypt depth (P = 0.01) in the duodenum. Jejunum and ileum measurements were influenced by the level and source of trace minerals (P < 0.05). Laying hens fed ZMCAA exhibited superior performance, egg quality, deposition of trace minerals in the egg yolk, and bone density compared to hens fed ZMCGly. In this study, older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.

Quantitative computed tomography of the liver in juvenile green sea turtles (Chelonia mydas).

Quantitative computed tomography (QCT) is a highly sensitive, applicable technique for determining the x-ray attenuation of organs. This technique reveals great precision in the detection of alterations in the x-ray attenuation of hepatic parenchyma, although the lack of studies establishing normal values limits its application in wild animals. The objective of this study was to establish mean hepatic attenuation values in four healthy juvenile sea turtles (Chelonia mydas) using QCT. Helical computed tomography scans were performed and regions of interest selected in the liver after multi-planar reconstruction images were obtained. The mean attenuation value for the hepatic parenchyma in these four turtles was 60.09 +/- 5.3 standard deviation Hounsfield units. Determining normal x-ray attenuation values of the liver increases knowledge of the computed tomographic anatomy of this species and may be useful in the investigation of hepatic diseases.