Fish Brain Research Articles

4′-(8-imidazole-octyloxy)-arctigenin efficiently inhibits spring viraemia of carp virus infection in vitro and in vivo

Spring viraemia of carp virus (SVCV), an important aquatic rhabdoviruses, causing devastating mortality in various carp species and other cultivated fish. In our previous studies, 4′-(8-Imidazole-octyloxy)-arctigenin (6A) with an eight carbon atoms of linker showed the higher activity against SVCV in EPC cells, based on the structure-activity relationship of 35 arctigenin derivatives. In this study, the antiviral activity and mechanism of 6A was further investigated both in vivo and in vitro. An analysis of survival curve of zebrafish indicated that 6A-treated group increased the survival rate by 23.4% and 20.0% following with 100 and 103 TCID50 doses of SVCV, respectively. Besides, 6A inhibited the gene expression of SVCV nucleoprotein and glycoprotein in brain, spleen, and liver at 4 and 7 d post-infection (dpi) by over 90% and 60%, respectively. Consistent with above results, there were no apparent signs of infection and inflammation in the brain, spleen and liver of the 6A-treated fish. However, we unexpectedly found an inability on 6A-treated zebrafish and EPC cells to mount a strong IFNф1 response to SVCV, which indicated that 6A inhibited SVCV replication not via the activation of IFNф1-related genes. Moreover, pre-treatment, co-treatment, and post-treatment of 6A with SVCV, 6A was observed to possess an intense antiviral response in the early stage of viral infection. Altogether, 6A was expected to be a therapeutic agent for the treatment of SVCV in aquaculture.

Dietary Euterpe oleracea Mart. attenuates seizures and damage to lipids in the brain of Colossoma macropomum.

The Amazonian açai fruit (Euterpe oleracea) has shown promising anticonvulsant properties, comparable to those of diazepam (BDZ) in in vivo models submitted to pentylenetetrazole (PTZ). PTZ is a classic convulsant agent used in studies for the purpose of screening anticonvulsants and investigating the mechanisms of epilepsy. Herein, we aimed to determine, for the first time, the effect of dietary administration of lyophilized E. oleracea (LEO) on PTZ-induced seizures, using juvenile Colossoma macropomum fish (9.1 ± 1.5g) as a model. A control diet (0.00% LEO) and two levels of LEO inclusion were established: 5.00% and 10.0% LEO (w/w). Fish were divided into five groups (n = 5): control (0.9% physiological solution; i.p.), PTZ (PTZ 150mgkg-1; i.p.), PTZ LEO 5.00%, PTZ LEO 10.0%, and BDZ-PTZ (BDZ: diazepam 10mgkg-1; i.p.). In addition to the electroencephalography (EEG), the lipid peroxidation (TBARS) was quantified in the brain, along with the characterization of behavioral responses. Fish receiving PTZ showed intense action potential bursts (APB), which overlapped with a hyperactive behavior. In PTZ LEO 5.00% and 10.0% groups, convulsive behavior was significantly reduced compared to the PTZ group. Fish fed 5.00% or 10.0% LEO and exposed to PTZ showed less excitability and lower mean amplitude in tracings. The inclusion of 10.0% LEO in the diet prevented the increase in mean amplitude of the EEG waves by 80%, without significant differences to the quantified mean amplitude of the BDZ-PTZ group. TBARS concentration was reduced by 60% in the brain of fish fed 10.0% LEO-enriched diets relative to the PTZ-administered group. The results of this study demonstrated the anticonvulsant and protective roles of LEO to the brain, and the dietary inclusion of LEO seems to be promising for the formulation of functional diets. Results of this study may boost the interest on the anti-seizurogenic properties of Euterpe oleracea, including the development of new approaches for the prevention of seizures in humans and animals with low epileptic threshold.

Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.

LRRK2 gain-of-function is considered a major cause of Parkinson’s disease (PD) in humans. However, pathogenicity of LRRK2 loss-of-function in animal models is controversial. Here we show that deletion of the entire zebrafish lrrk2 locus elicits a pleomorphic transient brain phenotype in maternal-zygotic mutant embryos (mzLrrk2). In contrast to lrrk2, the paralog gene lrrk1 is virtually not expressed in the brain of both wild-type and mzLrrk2 fish at different developmental stages. Notably, we found reduced catecholaminergic neurons, the main target of PD, in specific cell populations in the brains of mzLrrk2 larvae, but not adult fish. Strikingly, age-dependent accumulation of monoamine oxidase (MAO)-dependent catabolic signatures within mzLrrk2 brains revealed a previously undescribed interaction between LRRK2 and MAO biological activities. Our results highlight mzLrrk2 zebrafish as a tractable tool to study LRRK2 loss-of-function in vivo, and suggest a link between LRRK2 and MAO, potentially of relevance in the prodromic stages of PD.

Dietary Selenium reduces the toxic effect of Mercury on different organs (Brain, Gills, Kidney and Liver) of Rohu fish (Labeo rohita)

Because of improbably high partiality with antioxidant selenium to mercury, selenium isolates mercury and reduces its biological handiness to organisms. The present study investigates the effect of mercury (Hg) and selenium (Se) on the fingerling of Labeo rohita. The various sub-lethal concentrations of Hg i.e. 0.125µg/g, 0.250µg/g, and 0.500µg/g was used and incorporated in diet with a commercial diet (fish meal 40%, soya bean 33%, 3 % of vitamins premix, mineral premix and oil each and rice polish 18%). To understand how selenium reduces the toxic effect of mercury, fingerlings were exposed with 6ug/g Se singly and combined with doses of Hg. The effect of these heavy metals was observed after 24, 48, 72, and 96 hours in different organs of (Brain, Gills, Kidney and Liver) of Labeo rohita. The organs of exposed rohu showed significant changes in their microscopic anatomy in comparison to control. Prominent changes were observed in Hg treatments and found embody shrinkage of capillary, and dilation of the hollow lumen. In addition to the aforementioned changes vacuolation, peeling, hydropic swelling, and hyaline degeneration of hollow epithelium were also observed. Cysts and hamorrhage developed additionally seem in the organs of fish. Length of exposure seems to own a profound impact on organs because the increase in length of exposure enhanced the severity of histopathological damages. However, combined doses of metals cause reduction in the toxicity of mercury results in decrease damage in the shrinkage of capillary and dilation of the hollow lumen. During histological study vacuolation, hydropic swelling, and hyaline degeneration of hollow epithelium were also reduced. In Hg, the lethal concentration (LC50) was 0.374ug/g while when Hg and Se were combined, LC50 drops to 0.491ug/g. Results of this study suggest that exposure to Se helps to scale back the impact of mercury on mortality and different organs of Labeo rohita fingerling.

Immunohistochemical description of isotocin neurons and the anatomo-functional comparative analysis between isotocin and vasotocin systems in the weakly electric fish, Gymnotus omaroum

The vasopressin-vasotocin (AVP-AVT) and oxytocin-mesotocin-isotocin (OT-MT-IT) families of nonapeptides are of great importance in shaping context-dependent modulations of a conserved and yet highly plastic network of brain areas involved in social behavior: the social behavior network. The nonapeptide systems of teleost fish are highly conserved and share a common general organization. In this study, we first describe the presence of IT cells and projections in the brain of an electric fish, Gymnotus omarorum. Second, we confirm that IT neuron types and distribution in the preoptic area (POA) follow the same general pattern previously described in other teleost species. Third, we show that although IT and AVT neurons occur intermingled within the POA of G. omarorum and can be classified into the same subgroups, they present subtle but remarkable differences in size, number, and location. Finally, we show that unlike AVT, IT has no effect on basal electric signaling, reinforcing the specificity in the actions that each one of these nonapeptides has on social behavior and communication.

Dietary Seleno-l-Methionine Causes Alterations in Neurotransmitters, Ultrastructure of the Brain, and Behaviors in Zebrafish (Danio rerio)

Elevated concentrations of dietary selenium (Se) cause abnormalities and extirpation of fish inhabiting in Se-contaminated environments. However, its effect on fish behavior and the underlying mechanisms remain largely unknown. In this study, two-month-old zebrafish (Danio rerio) was fed seleno-l-methionine (Se-Met) at environmentally relevant concentrations (i.e., control (2.61), low (5.43), medium (12.16), and high (34.61) μg Se/g dry weight (dw), respectively, corresponding to the C, L, M, and H treatments) for 60 days. Targeted metabolomics, histopathological, and targeted transcriptional endpoints were compared to behavioral metrics to evaluate the effects of dietary exposure to Se-Met . The results showed that the levels of total Se and malondialdehyde in fish brains were increased in a dose-dependent pattern. Meanwhile, mitochondrial damages and decreased activities of the mitochondria respiratory chain complexes were observed in the neurons at the M and H treatments. In addition, dietary Se-Met affected neurotransmitters, metabolites, and transcripts of the genes associated with the dopamine, serotonin, gamma-aminobutyric acid, acetylcholine, and histamine signaling pathways in zebrafish brains at the H treatments. The total swimming distance and duration in the Novel Arm were lowered in fish from the H treatment. This study has demonstrated that dietary Se-Met affects the ultrastructure of the zebrafish brain, neurotransmitters, and associated fish behaviors and may help enhance adverse outcome pathways for neurotransmitter-behavior key events in zebrafish.

Seasonal expression and distribution of kisspeptin1 (kiss1) in the ovary and testis of freshwater catfish, Clarias batrachus: A putative role in steroidogenesis

The central role of kisspeptin (kiss) in mammalian reproduction is well established; however, its intra-gonadal role is poorly addressed. Moreover, studies investigating intra-gonadal role of kiss in fish reproduction are scanty, contradictory and inconclusive. The expression of kiss1 mRNA has been detected in the fish brain, and functionally attributed to the regulation of reproduction, feeding and behavior. The kiss1 mRNA has also been demonstrated in tissues other than the brain in some studies, but its cellular distribution and role at the tissue level have not been adequately addressed in fish. Therefore, an attempt was made in the present study to localize kiss1 in gonadal cells of the freshwater catfish, Clarias batrachus. This study reports the presence of kiss1 in the theca cells and granulosa cells of the ovarian oocytes and interstitial cells in the testis of the catfish. The role of kiss1 in the ovary and testis of the catfish was also investigated using kiss1 receptor (kiss1r) antagonist (p234). The p234 treatment decreased the production of 17β-estradiol in ovary and testosterone in the testis by lowering the activities of 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase under both, in vivo as well as in vitro conditions. The p234 treatment also arrested the progression of oogenesis, as evident from the low number of advancing/advanced oocytes in the treated ovary in comparison to the control ovary. It also reduced the area and perimeter of the seminiferous tubules in the treated catfish testis. Thus, our findings suggest that kiss is involved in the regulation of gonadal steroidogenesis, independent of known endocrine/ autocrine/ paracine regulators, and thereby it accelerates gametogenic processes in the freshwater catfish.

Amino Acid Carriers of the Solute Carrier Families 7 (SLC7) and 38 (SLC38) Are Involved in Leucine Sensing in the Brain of Atlantic Salmon (Salmo salar)

Sensing of amino acids in fish brain, especially branched-chain amino acids (BCAA) like leucine, is involved in regulation of feed intake through different mechanisms. However, there is limited information regarding the possible involvement of mechanisms dependent on amino acid carriers of the solute carrier families (SLC) known to be key regulators of intracellular leucine concentration, namely L-type amino acid transporter 1 (LAT1), and sodium-dependent neutral amino acid transporter 2 (SNAT2) and 9,(SNAT9), for which evidence of their participation is available in mammals. Comparative analysis amongst sequences revealed a complex pattern of paralogues in Atlantic salmon, for LAT1 (slc7a5aa, slc7a5ab, slc7a5ba, slc7a5bb, slc7a5ca, and slc7a5cb), SNAT2 (slc38a2a and slc38a2b) and SNAT9 (slc38a9). After establishing phylogenetic relationships of the different paralogues evaluated, samples of the selected brain areas were taken from Atlantic salmon to assess tissue distribution of transcripts. In an additional experiment, fish were fed two diets with different levels of leucine (high leucine: 35 g/kg vs. control leucine: 27.3 g/kg). The high leucine diet resulted in lower feed intake and increased mRNA abundance of specific paralogues of LAT1 (slc7a5aa, slc7a5ab, and slc7a5bb) and SNAT2 (slc38a2a and slc38a2b) though apparently not for SNAT9 in brain areas like hypothalamus and telencephalon involved in food intake regulation. The results obtained suggest a role for members of the SLC family in the anorectic effect of leucine and thus their involvement as additional amino acid sensing mechanism not characterised so far in fish regulation of feed intake.

Extremely dilution of Strychnos Nux vomica mitigates alcohol-induced reduction in enthalpies associated with free water molecules in fish brain

Background: Alcoholism is a global health problem. Extract of the seeds of Strychnos Nux vomica and its high dilution have long been used in homeopathy for alcohol induced diseases of patients. Alcoholism leads to reduced brain volume. Glial cells like astroglia contain large number of water channel proteins or aquaporin (AQP4) which mediate glial oedema resulting from ethanol intoxication. Nux vomica, a homeopathic drug of plant origin, is known to counteract alcohol effect. 
 Aim: The objective of this present study is to find out the level of free water molecules in the brain of a teleost fish under ethanol intoxication. The other purpose is to determine whether Nux vomica could restore the level of free water in the alcohol treated fish.
 Methodology: One group of fish was exposed to 456 mM ethanol for 30 min, another exposed first to a solution of Nux vomica 200c for 20 min and then to 456 mM ethanol for 30 min. The third group served as an untreated control. The mid brain of each fish was kept in an aluminium sample pan and its free water level was assessed by differential scanning calorimetry (DSC). Data were analyzed by ANOVA.
 Results and discussion: The results show that there was no significant variation in melting and freezing temperature of brain samples but the enthalpies, both freezing and melting varied significantly (P

Extremely Dilution of Strychnos Nux vomica Mitigates Alcohol-Induced Reduction in Enthalpies Associated With Free Water Molecules in a Fish Brain

Introduction
 Alcohol intoxication affects aquaporins in the glial cells of brain resulting in oedema. Nux vomica, a homeopathic drug of plant origin, is known to counteract alcohol effect. The objective of this present study is to find out the level of free water molecules in the brain of a teleost fish under ethanol intoxication. The second objective is to determine whether Nux vomica could restore the level of free water in the alcohol treated fish.
 Materials and methods
 One group of fish was exposed to 456 mM ethanol for 30 min, another exposed first to a solution of Nux vomica 200c for 20 min and then to 456 mM ethanol for 30 min. The third group served as an untreated control. The mid brain of each fish was kept in an aluminium sample pan and its free water level was assessed by differential scanning calorimetry (DSC). 
 Results
 All alcohol treated fish showed significant reduction in the level of free water molecules as compared to the untreated control. Treatment with Nux vomica increased the level of free water in the brain significantly as compared to the untreated alcoholic group.
 Conclusion
 Alcohol intoxication reduces free water molecules in the fish brain. Nux vom might have acted on aquaporins in the glial cells thereby increasing the level of free water in the brain.

Freshwater methamphetamine pollution turns brown trout into addicts

Human pollution is often evident from oil slicks and plastic drifting on shore, but many of the drugs that we consume also end up washing out into our water and current effluent treatment isn't equipped to deal with them. Drugs such as fluoxetine – also known as Prozac – creeping into our waterways can embolden fish and alter their behaviour, but pharmaceutical pollution doesn't end with prescribed medication. Illegal drugs, such as methamphetamine, can also accumulate in our waterways. ‘Whether illicit drugs alter fish behaviour at levels increasingly observed in surface water bodies was unclear’, says Pavel Horký from the Czech University of Life Sciences Prague, Czech Republic, so he and his colleagues, from the same university and the University of Southern Bohemia in České Budĕjovice, Czech Republic, decided to discover whether brown trout (Salmo trutta) are at risk of addiction from illegal methamphetamine in their waterways.After isolating brown trout in a tank of water laced with 1 μg l–1 methamphetamine (a level that has been found in freshwater rivers) for 8 weeks, Horký and colleagues transferred the fish to a freshwater tank and checked whether the animals were experiencing withdrawal – offering them a choice between freshwater or water containing methamphetamine – every alternate day for 10 days. If the fish had become addicted to the low levels of methamphetamine in their water, they would be feeling the effects of withdrawal and would seek the drug when it was available.Tracking the fish's choices, it was clear to the team that the trout that had spent 2 months in methamphetamine-contaminated water had become addicted, selecting water containing the drug as they suffered withdrawal during the first 4 days after moving to freshwater. In addition, the addicted fish were less active than trout that had never experienced the drug, and the researchers found evidence of the drug in the fish's brains up to 10 days after the methamphetamine was withdrawn. It seems that even low levels of illicit drugs in our waterways can affect the animals that reside there.Horký is also concerned that drug addiction could drive fish to congregate near unhealthy water treatment discharges in search of a fix, as well as disturbing their natural tempo of life. ‘The elicitation of drug addiction in wild fish could represent another example of unexpected pressure on species living in urban environments’, he suggests.

Methamphetamine pollution elicits addiction in wild fish.

Illicit drug abuse presents pervasive adverse consequences for human societies around the world. Illicit drug consumption also plays an unexpected role in contamination of aquatic ecosystems that receive wastewater discharges. Here, we show that methamphetamine, considered as one of the most important global health threats, causes addiction and behavior alteration of brown trout Salmo trutta at environmentally relevant concentrations (1 µgl-1). Altered movement behavior and preference for methamphetamine during withdrawal were linked to drug residues in fish brain tissues and accompanied by brain metabolome changes. Our results suggest that emission of illicit drugs into freshwater ecosystems causes addiction in fish and modifies habitat preferences with unexpected adverse consequences of relevance at the individual and population levels. As such, our study identifies transmission of human societal problems to aquatic ecosystems.

Role of the G protein-coupled receptors GPR84 and GPR119 in the central regulation of food intake in rainbow trout.

We evaluated the role of the G protein-coupled receptors GPR84 and GPR119 in food intake regulation in fish using rainbow trout (Oncorhynchus mykiss) as a model. In the first experiment, we assessed the effects on food intake of intracerebroventricular treatment with agonists of these receptors. In the second experiment, we assessed the impact of the same treatments on mRNA abundance in the hypothalamus and hindbrain of neuropeptides involved in the metabolic control of food intake (npy, agrp1, pomca1 and cartpt) as well as in changes in parameters related to signalling pathways and transcription factors involved in the integrative response leading to neuropeptide production. Treatment with both agonists elicited an anorectic response in rainbow trout attributable to changes observed in the mRNA abundance of the four neuropeptides. Changes in neuropeptides relate to changes observed in mRNA abundance and phosphorylation status of the transcription factor FOXO1. These changes occurred in parallel with changes in the phosphorylation status of AMPKα and Akt, the mRNA abundance of mTOR as well as signalling pathways related to PLCβ and IP3. These results allow us to suggest that (1) at least part of the capacity of fish brain to sense medium-chain fatty acids such as octanoate depends on the function of GPR84, and (2) the capacity of fish brain to sense N-acylethanolamides or triglyceride-derived molecules occurs through the binding of these ligands to GPR119.

Three-Dimensional Imaging of Whole-Body Zebrafish Revealed Lipid Disorders Associated with Niemann-Pick Disease Type C1.

Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann-Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. The constructed 3D fish model provided comprehensive information on the 3D distribution of lipids of interest and allowed direct correlations between these lipids and organs of the fish. Obtained results revealed that several sphingolipids and phospholipids showed significant alterations and exhibited different localization patterns in various organs such as the brain, spinal cord, intestines, and liver-spleen region in the npc1 gene mutant fish compared to those of the wild type. The whole-body 3D MALDI-MSI approach revealed unique lipid signatures for different NPC1-affected organs, which might offer insights into the link between the impaired lipid storage and subsequent clinical symptoms, such as neurodegeneration and hepatosplenomegaly.

Induction of oxidative stress and apoptosis in the injured brain: potential relevance to brain regeneration in zebrafish.

Recent findings suggest a significant role of the brain-derived neurotrophic factor (BDNF) as a mediator of brain regeneration following a stab injury in zebrafish. Since BDNF has been implicated in many physiological processes, we hypothesized that these processes are affected by brain injury in zebrafish. Hence, we examined the impact of stab injury on oxidative stress and apoptosis in the adult zebrafish brain. Stab wound injury (SWI) was induced in the right telencephalic hemisphere of the adult zebrafish brain and examined at different time points. The biochemical variables of oxidative stress insult and transcript levels of antioxidant genes were assessed to reflect upon the oxidative stress levels in the brain. Immunohistochemistry was performed to detect the levels of early apoptotic marker protein cleaved caspase-3, and the transcript levels of pro-apoptotic and anti-apoptotic genes were examined to determine the effect of SWI on apoptosis. The activity of antioxidant enzymes, the level of lipid peroxidation (LPO) and reduced glutathione (GSH) were significantly increased in the injured fish brain. SWI also enhanced the expression of cleaved caspase-3 protein and apoptosis-related gene transcripts. Our results indicate induction of oxidative stress and apoptosis in the telencephalon of adult zebrafish brain by SWI. These findings contribute to the overall understanding of the pathophysiology of traumatic brain injury and adult neurogenesis in the zebrafish model and raise new questions about the compensatory physiological mechanisms in response to traumatic brain injury in the adult zebrafish brain.

Assessment of DNA Damage and Apoptosis in the Brain of Freshwater Fish <i>Oreochromis mossambicus</i> Exposed to Tannery Effluent Wastewater

The present study was designed to evaluate the effect of tannery effluent on the fingerlings of freshwater fish Oreochromis mossambicus. The fishes were maintained at 10% concentration of tannery effluent for a period of 30 days. Apoptosis was studied by activity of caspases. Caspase 3 and 9 activity showed significant alteration. DNA seperation by agarose gel electrophoresis shows difference in intensity of genomic DNA between 750-1000 bp in fishes exposed to tannery effluent. DNA damage was also confirmed by Comet assay which showed an increase in DNA damage and tail migration was indicated by increase in percentage of mean DNA comet tail length formation.

A Confocal Microscopic Study of Gene Transfer into the Mesencephalic Tegmentum of Juvenile Chum Salmon, Oncorhynchus keta, Using Mouse Adeno-Associated Viral Vectors.

To date, data on the presence of adenoviral receptors in fish are very limited. In the present work, we used mouse recombinant adeno-associated viral vectors (rAAV) with a calcium indicator of the latest generation GCaMP6m that are usually applied for the dorsal hippocampus of mice but were not previously used for gene delivery into fish brain. The aim of our work was to study the feasibility of transduction of rAAV in the mouse hippocampus into brain cells of juvenile chum salmon and subsequent determination of the phenotype of rAAV-labeled cells by confocal laser scanning microscopy (CLSM). Delivery of the gene in vivo was carried out by intracranial injection of a GCaMP6m-GFP-containing vector directly into the mesencephalic tegmentum region of juvenile (one-year-old) chum salmon, Oncorhynchus keta. AAV incorporation into brain cells of the juvenile chum salmon was assessed at 1 week after a single injection of the vector. AAV expression in various areas of the thalamus, pretectum, posterior-tuberal region, postcommissural region, medial and lateral regions of the tegmentum, and mesencephalic reticular formation of juvenile O. keta was evaluated using CLSM followed by immunohistochemical analysis of the localization of the neuron-specific calcium binding protein HuCD in combination with nuclear staining with DAPI. The results of the analysis showed partial colocalization of cells expressing GCaMP6m-GFP with red fluorescent HuCD protein. Thus, cells of the thalamus, posterior tuberal region, mesencephalic tegmentum, cells of the accessory visual system, mesencephalic reticular formation, hypothalamus, and postcommissural region of the mesencephalon of juvenile chum salmon expressing GCaMP6m-GFP were attributed to the neuron-specific line of chum salmon brain cells, which indicates the ability of hippocampal mammal rAAV to integrate into neurons of the central nervous system of fish with subsequent expression of viral proteins, which obviously indicates the neuronal expression of a mammalian adenoviral receptor homolog by juvenile chum salmon neurons.

Indices of the DNA repair system in the brain of fish as a biomarker of inorganic mercury burden

Mercury is a widespread heavy metal that causes a stable and prolonged environmental pollution. Low concentrations of inorganic and organic mercury compounds are found in almost all water bodies. The high level of mercury bioaccumulation is a cause of tissue-specific toxicity, including neurotoxicity. Absorbed in nervous tissue mercury can cause brain disorders both in neural and glial cells. The brain of fish is considered one of the most susceptible targets for cytotoxicity of mercury in aquatic ecosystems. Taking into account that different forms of mercury have widespread distribution and exhibit a strong neurotoxic effect, the assessment of mercury cytotoxicity in the brain of fish is relevant and extremely important. Rainbow trout Oncorhynchus mykiss was exposed to mercury chloride in the dose range of 5-20 μg/L for 60 days to study the chronic exposure of low doses. In this paper, we studied the influence of inorganic mercury on oxidative stress, DNA repair proteins – ERCC1 and PARP1 in the trout’s brain. The results obtained have shown that the chronic effect of inorganic mercury causes dose-dependent oxidative stress in the fish brain. In addition, low concentrations of mercury (10 and 20 μg/L) caused a decrease in the content of ERCC1 in the brain of fish. On the contrary, the same doses have caused an increase in PARP1 expression. That is the chronic influence of low concentrations of inorganic mercury has a negative effect in the fish brain. Observed results showed that inorganic mercury has a potential for suppressing DNA repair and, therefore, increases the instability of genome. Thus, ERCC1 and PARP1 can be considered as the sensitive biomarkers of mercury cytotoxicity in the fish brain. A further study of mercury neurotoxicity is needed to find out the hazard of mercury environmental pollution as well as a validation of biomarkers of their impact.

Regenerative field effect transistor biosensor for in vivo monitoring of dopamine in fish brains

The detection of dopamine, one of the neurotransmitters in cerebral physiology, is critical in studying brain activities and understanding brain functions. However, regenerative biosensor for monitoring dopamine in the progress of physiological and pathological events is still challenging, due to lack of the platform for repetitive on-line detection-regeneration cycle. Herein, we have developed a regenerated field effect transistor (FET) combined with in vivo monitoring system. In this biosensor, gold-coated magnetic nanoparticles (Fe3O4@AuNPs) acts as a regenerated recognition unit for dopamine. Just by simple removal of a permanent magnet, dopamine on the biosensor interface are catalyzed by tyrosinase, thus achieving the regeneration of the biosensor. As a result, this FET biosensor not only reveals high sensitivity and selectivity, but also exhibits excellent stability after 15 regeneration processing. This biosensor is capable of monitor dopamine with a linear range between 1 μmol L−1 and 120 μmol L−1 and low detection limit (DL) of 3.3 nmol L−1. Then, the platform has been successfully applied in dopamine analysis in fish brain under global cerebral cortical neurons. This FET biosensor is the first to on-line and remote control the sensitivity and DL by permanent magnet. It opens the door to reusable, inexpensive and large-scale productions.

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder.

Opioid use disorder (OUD) has become a leading cause of death in the United States, yet current therapeutic strategies remain highly inadequate. To identify potential treatments for OUD, we screened a targeted selection of over 100 drugs using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride reduced the physical signs associated with opioid withdrawal. In rat models of neuropathic pain, finasteride did not alter the antinociceptive effect of opioids and reduced withdrawal-induced hyperalgesia. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish in a fashion akin to the effects of finasteride. These results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new treatment option for this disorder.