The impact of adult neurogenesis on affective functions: of mice and men.

In most mammals, new neurons are not only produced during embryogenesis but also after birth. Soon after adult neurogenesis was discovered, the influence of recruiting new neurons on cognitive functions, especially on memory, was documented. Likewise, the late process of neuronal production also contributes to affective functions, but this outcome was recognized with more difficulty. This review covers hypes and hopes of discovering the influence of newly-generated neurons on brain circuits devoted to affective functions. If the possibility of integrating new neurons into the adult brain is a commonly accepted faculty in the realm of mammals, the reluctance is strong when it comes to translating this concept to humans. Compiling data suggest now that new neurons are derived not only from stem cells, but also from a population of neuroblasts displaying a protracted maturation and ready to be engaged in adult brain circuits, under specific signals. Here, we discuss the significance of recruiting new neurons in the adult brain circuits, specifically in the context of affective outcomes. We also discuss the fact that adult neurogenesis could be the ultimate cellular process that integrates elements from both the internal and external environment to adjust brain functions. While we must be critical and beware of the unreal promises that Science could generate sometimes, it is important to continue exploring the potential of neural recruitment in adult primates. Reporting adult neurogenesis in humankind contributes to a new vision of humans as mammals whose brain continues to develop throughout life. This peculiar faculty could one day become the target of treatment for mental health, cognitive disorders, and elderly-associated diseases. The vision of an adult brain which never stops integrating new neurons is a real game changer for designing new therapeutic interventions to treat mental disorders associated with substantial morbidity, mortality, and social costs.

Functional connectivity of the amygdala subnuclei in various mood states of bipolar disorder.

Amygdala functional dysconnectivity lies at the heart of the pathophysiology of bipolar disorder (BD). Recent preclinical studies suggest that the amygdala is a heterogeneous group of nuclei, whose specific connectivity could drive positive or negative emotional valence. We investigated functional connectivity (FC) changes within these circuits emerging from each amygdala's subdivision in 127 patients with BD in different mood states and 131 healthy controls (HC), who underwent resting-state functional MRI. FC was evaluated between lateral and medial nuclei of amygdalae, and key subcortical regions of the emotion processing network: anterior and posterior parts of the hippocampus, and core and shell parts of the nucleus accumbens. FC was compared across groups, and subgroups of patients depending on their mood states, using linear mixed models. We also tested correlations between FC and depression (MADRS) and mania (YMRS) scores. We found no difference between the whole sample of BD patients vs. HC but a significant correlation between MADRS and right lateral amygdala /right anterior hippocampus, right lateral amygdala/right posterior hippocampus and right lateral amygdala/left anterior hippocampus FC (r = -0.44, r = -0.32, r = -0.27, respectively, all pFDR<0.05). Subgroup analysis revealed decreased right lateral amygdala/right anterior hippocampus and right lateral amygdala/right posterior hippocampus FC in depressed vs. non-depressed patients and increased left medial amygdala/shell part of the left nucleus accumbens FC in manic vs non-manic patients. These results demonstrate that acute mood states in BD concur with FC changes in individual nuclei of the amygdala implicated in distinct emotional valence processing. Overall, our data highlight the importance to consider the amygdala subnuclei separately when studying its FC patterns including patients in distinct homogeneous mood states.

Behavior of diclofenac from contaminated fish after cooking and in vitro digestion.

BACKGROUND: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4'-hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g-1) and submitted to three culinary treatments (roasting, steaming and grilling). RESULTS: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1-98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4'-hydroxydiclofenac was not detected after cooking or digestion. CONCLUSION: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Temporal trends of persistent organic pollutant contamination in Franciscana dolphins from the Southwestern Atlantic.

Persistent organic pollutants (POPs) were analyzed in 136 blubber samples of Franciscana dolphins from Brazil (Pontoporia blainvillei), which is the most threatened dolphin in the Southwestern Atlantic. The dolphins were caught by the fishery fleet and collected from 2000 to 2018 in three regions of São Paulo state: northern São Paulo (SPN), central São Paulo (SPC), and southern São Paulo (SPS). The POPs analyzed in this study were polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDTs), Mirex, hexachlorobenzene (HCB), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), and polybrominated diphenyl ethers (PBDEs). The concentrations ranged from 36 to 7200 ng g-1 lipid weight (lw) and 113-42200 ng g-1 lw for predominant compounds DDTs and PCBs, respectively. Similar profiles of PCB congeners were observed with a predominance of hexachlorinated compounds, representing approximately 50% of the total PCB amount; the highest PCB concentrations were observed from Baixada Santista (SPC) proximate to a highly urbanized and industrial coastal area. Significant differences were observed between the sexes and maturity of dolphins, mainly for PCBs, DDTs, and Mirex. In general, POPs other than HCB in Franciscana dolphins showed downward temporal trends, matching the regulatory periods for restricting and/or banning these compounds. Although POP concentrations are declining, PCB levels remain high in small dolphins, suggesting adverse health effects on Franciscanas. As organic contaminants are one of the numerous threats Franciscanas have been vulnerable to along the Brazilian coast, we recommend monitoring POPs levels every five years to check for declining (or stabilizing) trends.

Survey on endocrine-disrupting chemicals in seafood: Occurrence and distribution.

Currently, the presence of endocrine disrupting chemicals (EDCs) in the marine environment pose а potential risk to both wildlife and human health. The occurrence of EDCs in seafood depends of several factors such as source and amounts of EDCs that reach the aquatic environment, physicochemical features of EDCs, and its accumulation in trophic chain. This review highlights the occurrence and distribution of EDCs along the seafood in the last 6 years. The following EDCs were included in this review: brominated flame retardants (PBDEs, PBBs, HBCDDs, TBBPA, and novel flame retardants); pharmaceuticals (paracetamol, ibuprofen, diclofenac, carbamazepine), bisphenols, hormones, personal care products (Musk and UV Filters), and pesticides (organochlorides, organophosphates, and pyrethroids). Some of them were found above the threshold that may cause negative effects on human, animal, and environmental health. More control in some countries, as well as new legislation and inspection over the purchase, sale, use, and production of these compounds, are urgently needed. This review provides data to support risk assessment and raises critical gaps to stimulate and improve future research.

Adult-born neurons boost odor-reward association.

Olfaction is an important sensory modality driving fundamental behaviors. During odor-dependent learning, a positive value is commonly assigned to an odorant, and multiple forms of plasticity are involved when such odor-reward associations are formed. In rodents, one of the mechanisms underlying plasticity in the olfactory bulb consists in recruiting new neurons daily throughout life. However, it is still unknown whether adult-born neurons might participate in encoding odor value. Here, we demonstrate that exposure to reward-associated odors specifically increases activity of adult-born neurons but not preexisting neurons. Remarkably, adult-born neuron activation during rewarded odor presentation heightens discrimination learning and enhances the ability to update the odor value during reversal association. Moreover, in some cases, activation of this interneuron population can trigger olfactory learning without sensory stimulation. Taken together, our results show a specific involvement of adult-born neurons in facilitating odor-reward association during adaptive learning.

Clinical signs in free-ranging Guiana dolphins Sotalia guianensis during a morbillivirus epidemic: case study in Sepetiba Bay, Brazil.

From November 2017 to March 2018, a cetacean morbillivirus (CeMV) outbreak caused an unprecedented mass mortality among Guiana dolphins Sotalia guianensis in Ilha Grande Bay and Sepetiba Bay, Rio de Janeiro, Brazil. Small boat surveys were conducted to document the behavior and clinical signs presented by diseased dolphins. We observed 5 abnormally behaving, disoriented Guiana dolphins on separate days, of which 1 died stranded and 2 sank. Signs of ataxia included difficulties with swimming and maintaining a course, balance and buoyancy. At least 40 other individuals were emaciated, and 10 photo-identified dolphins had miscellaneous skin lesions, some ulcerated. Labored breathing suggestive of airway obstruction was heard in several groups. These neurological, respiratory and cutaneous signs may comprise part of the clinical constellation of CeMV infection in dolphins. The combined threat of anthropogenic pressures and CeMV lethal disease is of concern for the survival of the Guiana dolphin population in Sepetiba Bay.

Nontargeted Screening of Halogenated Organic Compounds in Bottlenose Dolphins (Tursiops truncatus) from Rio de Janeiro, Brazil.

To catalog the diversity and abundance of halogenated organic compounds (HOCs) accumulating in high trophic marine species from the southwestern Atlantic Ocean, tissue from bottlenose dolphins (Tursiops truncatus) stranded or incidentally captured along the coast of Rio de Janeiro, Brazil, were analyzed by a nontargeted approach based on GC×GC/TOF-MS. A total of 158 individual HOCs from 32 different structural classes were detected in the blubber of 4 adult male T. truncatus. Nearly 90% of the detected compounds are not routinely monitored in the environment. DDT-related and mirex/dechlorane-related compounds were the most abundant classes of anthropogenic origin. Methoxy-brominated diphenyl ethers (MeO-BDEs) and chlorinated methyl- and dimethyl bipyrroles (MBPs and DMBPs) were the most abundant natural products. Reported for the first time in southwestern Atlantic cetaceans and in contrast to North American marine mammals, chlorinated MBPs and DMBPs were more abundant than their brominated and/or mixed halogenated counterparts. HOC profiles in coastal T. truncatus from Brazil and California revealed a distinct difference, with a higher abundance of MeO-BDEs, mirex/dechloranes and chlorinated bipyrroles in the Brazilian dolphins. Thirty-six percent of the detected HOCs had an unknown structure. These results suggest broad geographical differences in the patterns of bioaccumulative chemicals found in the marine environment and indicate the need to develop more complete catalogs of HOCs from various marine environments.

Coumarin heterocyclic derivatives: chemical synthesis and biological activity.

This review highlights the broad range of science that has arisen from the synthesis of coumarin-linked and fused heterocycle derivatives. Specific topics include their synthesis and biological activity.

First assessment of persistent organic pollutants and halogenated natural compounds in an omnivorous resident coral-reef fish species, black triggerfish, Melichthys niger, from an Atlantic oceanic island, Brazil.

Studies on the occurrence of POPs and other persistent compounds in pristine areas are extremely valuable, as they offer insights on the long-range transportation of POPs and the occurrence of natural compound producers' areas. In this regard, this study aimed to report data of both anthropogenic (polychlorinated biphenyls, PCBs, and polybrominated diphenyl ethers, PBDEs) and natural (methoxylated PBDEs, MeO-BDEs) compounds in tissues of the black triggerfish, Melichthys niger (Tetraodontiformes, Balistidae), specimens (n = 30) sampled in 2018 during a scientific expedition conducted at Trindade Island. Concentrations of ∑28PCBs ranged from 73 to 1052 ng g-1 lw in liver, 334 to 1981 ng g-1 lw in gonads, and 20 to 257 ng g-1 lw in muscle, with the predominance of PCB-180 in liver and PCB-52 in gonad and muscle. Concentrations of ∑7PBDEs ranged from

First determination of UV filters in marine mammals. Octocrylene levels in Franciscana dolphins.

Most current bioexposure assessments for UV filters focus on contaminants concentrations in fish from river and lake. To date there is not information available on the occurrence of UV filters in marine mammals. This is the first study to investigate the presence of sunscreen agents in tissue liver of Franciscana dolphin (Pontoporia blainvillei), a species under special measures for conservation. Fifty six liver tissue samples were taken from dead individuals accidentally caught or found stranded along the Brazilian coastal area (six states). The extensively used octocrylene (2-ethylhexyl-2-cyano-3,3-diphenyl-2-propenoate, OCT) was frequently found in the samples investigated (21 out of 56) at concentrations in the range 89-782 ng·g(-1) lipid weight. São Paulo was found to be the most polluted area (70% frequency of detection). Nevertheless, the highest concentration was observed in the dolphins from Rio Grande do Sul (42% frequency of detection within that area). These findings constitute the first data reported on the occurrence of UV filters in marine mammals worldwide.

Evaluation of the Stability of a 1,8-Cineole Nanoemulsion and Its Fumigant Toxicity Effect against the Pests Tetranychus urticae, Rhopalosiphum maidis and Bemisia tabaci.

Pest control is a main concern in agriculture. Indiscriminate application of synthetic pesticides has caused negative impacts leading to the rapid development of resistance in arthropod pests. Plant secondary metabolites have been proposed as a safer alternative to conventional pesticides. Monoterpenoids have reported bioactivities against important pests; however, due to their high volatility, low water solubility and chemical instability, the application of these compounds has been limited. Nanosystems represent a potential vehicle for the broad application of monoterpenoids. In this study, an 1,8-cineole nanoemulsion was prepared by the low energy method of phase inversion, characterization of droplet size distribution and polydispersity index (PDI) was carried out by dynamic light scattering and stability was evaluated by centrifugation and Turbiscan analysis. Fumigant bioactivity was evaluated against Tetranychus urticae, Rhopalosiphum maidis and Bemisia tabaci. A nanoemulsion with oil:surfactant:water ratio of 0.5:1:8.5 had a droplet size of 14.7 nm and PDI of 0.178. Formulation was stable after centrifugation and the Turbiscan analysis showed no particle migration and a delta backscattering of ±1%. Nanoemulsion exhibited around 50% more bioactivity as a fumigant on arthropods when compared to free monoterpenoid. These results suggest that nanoformulations can provide volatile compounds of protection against volatilization, improving their bioactivity.

Assessing positive and negative valence systems to refine animal models of bipolar disorders: the example of GBR 12909-induced manic phenotype.

Bipolar disorders are defined by recurrences of depressive and manic episodes. The pathophysiology is still unknown, and translating clinical symptoms into behaviors explorable in animal models is challenging. Animal models of bipolar disorder do not exist because cyclicity of the disease is impossible to mimic, and it is therefore necessary to study mania and depression models separately. Beyond mood, emotional biases differentiate bipolar states in humans. Mania is associated with positive biases, e.g. emotional stimuli become more rewarding and less aversive, and the opposite for depression. We propose to assess behavioral hedonic responses to innately appetitive and aversive olfactory and gustatory cues in mice as proxies for the assigned emotional valence. A mania model is therefore supposed to exhibit positive hedonic bias. Using the GBR 12909 mania model, we observed the classical hyperactivity phenotype, along with low depressive-like but high anxiety-like behaviors. Unexpectedly, GBR 12909-treated mice exhibited strong negative hedonic biases. Consequently, the GBR 12909 model of mania might not be appropriate for studying emotional disturbances associated with mania states. We propose olfactory and gustatory preference tests as crucial assessment for positive and negative valence biases, necessary for precisely characterizing animal models of bipolar disorders.

Agrochemical Residues in Fish and Bivalves from Sepetiba Bay and Parnaiba River Delta, Brazil.

Accumulation of pesticides has a harmful impact on the environment and human health. The main goal of this work was to develop a method to determine and quantify the residues of thirteen pesticides in edible fish and bivalves such as parati (Mugil curema), seabass (Centropomus ssp.), mullet (Mugil brasiliensis), clams (Anomalocardia brasiliana) and mussel (Mytilus galloprovincialis) collected from Sepetiba Bay and Parnaiba River Delta (Brazil) between 2019 and 2020. Matrix solid-phase dispersion (MSPD) was used for extraction and quantification through gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). The method was validated (linearity, accuracy and precision) for fatty fish (Salmo salar), lean fish (Mugil curema) and bivalves (Mytilus edulis). The survey found linear correlation coefficients (r) equal to or greater than 0.9 for almost all analytes. The relative standard deviations (RSD) of five replicates were less than 20% for almost all analytes at different concentrations in lean fish, fatty fish and bivalves. Most analytes showed satisfactory accuracy. Alachlor herbicide was found in samples of seabass, mussels, clams and parati with levels ranging between 0.55 to 420.39 µg kg-1 dw. Ethion was found in parati (maximum 211.22 µg kg-1 dw), mussels (15.1 µg kg-1 dw) and clams (maximum 44.50 µg kg-1 dw). Alachlor was found in clams (maximum 93.1 µg kg-1 dw), and bifenthrin was found in parati (maximum 43.4 µg kg-1 dw) and clams (maximum 42.21 µg kg-1 dw). The validated method was satisfactory for the determination of eleven pesticides in the fatty fish matrix, and thirteen pesticides in the samples of lean fish and bivalves. The presence of alachlor, ethion and bifenthrin stands out.

Occurrence of pharmaceuticals in seafood from two Brazilian coastal areas: Implication for human risk assessment.

Pharmaceuticals (PhACs) are considered emerging contaminants with potential accumulation in aquatic organisms. Thus, seafood consumption may cause long-term effects and health risk for consumers. In the present study, the occurrence of PhACs in seafood from two Brazilian coastal areas, Sepetiba Bay (n = 43) and Parnaiba Delta River (n = 48), was determined for the first time, and their potential risk for human health was assessed. An eco-friendly multi-analytes method was used, after being validated for the different types of matrices (mussels, fatty and lean fish). All compounds under study were detected at least in four seafood species, including chloramphenicol, an antibiotic prohibited in animal foods. Most PhACs had mean concentrations below limit of quantification. Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs), as well as simvastatin and carbamazepine were the main PhACs bioaccumulated in edible parts of seafood species from Brazil. The high trophic level carnivorous species, snook, was the most contaminated by NSAIDs, while bivalves were the seafood more contaminated by lipid regulators. The profile of contamination did not vary among different types of matrix, except in relation to carbamazepine and ketoprofen. These PhACs were more abundant in species from Sepetiba Bay, an area highly impacted by human influence. The estimated daily exposure for Brazilian population that consumes the studied species was up to 20.3 ng/kg bw/day via carib pointed-venus and 25.7 ng/kg bw/day via snooks, lower than acceptable daily intake. Thus, consumption of seafood species from Sepetiba Bay and Parnaiba Delta River seems to be safe to the population in what concerns the PhACs studied.

Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2.

The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of Bmal1 or Per2 from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of Gpr88. Whereas the conditional knockout of Bmal1 and Per2 had mild effects on affective behaviors, a pronounced effect on motor functions was found in Bmal1 knockout mice. Subsequent investigation revealed an attenuated response of Bmal1 knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of Bmal1 within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice.

Obtention of biodiesel through an enzymatic two-step process. Study of its performance and characteristic emissions.

We describe the enzymatic synthesis of biodiesel from waste cooking oil (WCO) in a two-step production process: hydrolysis of WCO, followed by acid-catalyzed esterification of free fatty acids (FFAs). Among the three commercial enzymes evaluated, the inexpensive lipase Lipex® 100L supported on Lewatit® VP OC 1600 produced the best overall biodiesel yield (96.3%). Finally, we assessed the combustion efficiency of the obtained biodiesel and its blends. All blends tested presented lower emissions of CO and HC compared to diesel. The NOx emissions were higher due to biodiesel's high volatility and viscosity. The cost of biodiesel production was calculated using the process described.

How, when, and where new inhibitory neurons release neurotransmitters in the adult olfactory bulb.

Adult-born neurons continuously incorporate into the olfactory bulb where they rapidly establish contacts with a variety of synaptic inputs. Little is known, however, about the functional properties of their output. Characterization of synaptic outputs from new neurons is essential to assess the functional impact of adult neurogenesis on mature circuits. Here, we used optogenetics to control neurotransmitter release from new neurons. We found that light-induced synaptic GABA release from adult-born neurons leads to profound modifications of postsynaptic target firing patterns. We revealed that functional output synapses form just after new cells acquire the faculty to spike, but most synapses were made a month later. Despite discrepancies in the timing of new synapse recruitment, the properties of postsynaptic signals remain constant. Remarkably, we found that all major cell types of the olfactory bulb circuit, including output neurons and several distinct subtypes of local interneurons, were contacted by adult-born neurons. Thus, this study provides new insights into how new neurons integrate into the adult neural network and may influence the sense of smell.

Equatorial Atlantic pelagic predators reveal low content of PBDEs in contrast to MeO-BDEs: An analysis of brominated diphenyl ethers in blue shark and yellowfin tuna.

Polybrominated diphenyl ethers (PBDEs) and their methoxylated analogues (MeO-BDEs) are widely distributed in the environment. The main concern about the presence of PBDEs and MeO-BDEs in fish is due to their potential endocrine disruption effects in the specimens, and their potential risk to the health of human consumers. Considering these concerns, the goal of this study was to investigate the occurrence of PBDEs and MeO-BDEs in muscle tissues of blue shark (BSH), Prionace glauca, and yellowfin tuna (YFT), Thunnus albacares, caught in the Equatorial Atlantic Ocean (EAO), North-eastern Brazilian waters, and to evaluate the potential risk of human exposure by consumption. Muscle tissues of YFT and BSH were extracted using a Soxhlet apparatus and an Accelerated Solvent Extractor (ASE), respectively. PBDEs and MeO-BDEs were analysed by GC-NCI-MS. Concentrations of PBDEs ranged from not detected (nd) to 10 ng g-1 lipid weight (lw) in YFT muscle samples, while PBDE levels in BSH muscle samples ranged from

Tanshinones and their Derivatives: Heterocyclic Ring-Fused Diterpenes of Biological Interest.

The available scientific literature regarding tanshinones is very abundant, and after its review, it is noticeable that most of the articles focus on the properties of tanshinone I, cryptotanshinone, tanshinone IIA, sodium tanshinone IIA sulfonate and the dried root extract of Salvia miltiorrhiza (Tan- Shen). However, although these products have demonstrated important biological properties in both in vitro and in vivo models, their poor solubility and bioavailability have limited their clinical applications. For these reasons, many studies have focused on the search for new pharmaceutical formulations for tanshinones, as well as the synthesis of new derivatives that improve their biological properties. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2015) on tanshinones in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we offer an update on the last five years of new research on these quinones, focusing on their synthesis, biological activity on noncommunicable diseases and drug delivery systems, to support future research on its clinical applications.