Parental exposure to antidepressants has lasting effects on offspring? A case study with zebrafish.

Fish have common neurotransmitter pathways with humans, exhibiting a significant degree of conservation and homology. Thus, exposure to fluoxetine makes fish potentially susceptible to biochemical and physiological changes, similarly to what is observed in humans. Over the years, several studies demonstrated the potential effects of fluoxetine on different fish species and at different levels of biological organization. However, the effects of parental exposure to unexposed offspring remain largely unknown. The consequences of 15-day parental exposure to relevant concentrations of fluoxetine (100 and 1000 ng/L) were assessed on offspring using zebrafish as a model organism. Parental exposure resulted in offspring early hatching, non-inflation of the swimming bladder, increased malformation frequency, decreased heart rate and blood flow, and reduced growth. Additionally, a significant behavioral impairment was also found (reduced startle response, basal locomotor activity, and altered non-associative learning during early stages and a negative geotaxis and scototaxis, reduced thigmotaxis, and anti-social behavior at later life stages). These behavior alterations are consistent with decreased anxiety, a significant increase in the expression of the monoaminergic genes slc6a4a (sert), slc6a3 (dat), slc18a2 (vmat2), mao, tph1a, and th2, and altered levels of monoaminergic neurotransmitters. Alterations in behavior, expression of monoaminergic genes, and neurotransmitter levels persisted until offspring adulthood. Given the high conservation of neuronal pathways between fish and humans, data show the possibility of potential transgenerational and multigenerational effects of pharmaceuticals' exposure. These results reinforce the need for transgenerational and multigenerational studies in fish, under realistic scenarios, to provide realistic insights into the impact of these pharmaceuticals.

Acute exposure to tenorite nanoparticles induces phenotypic and behavior alterations in zebrafish larvae.

Tenorite or copper oxide nanoparticles (CuO NPs) are extensively used in biomedical fields due to their unique physicochemical properties. Increased usage of these NPs leads to release in the environment, affecting varied ecosystems and the biota within them, including humans. The effect of these NPs can be evaluated with zebrafish, an excellent complementary model for nanotoxicity studies. Previous reports focusing on CuO NPs-induced teratogenicity in zebrafish development have not elucidated the phenotypical changes in detail. In most of the studies, embryos at 3 hpf with a protective chorion layer were exposed to CuO NPs, and their effect on the overall developmental process is studied. Hence, in this study, we focused on the effect of acute exposure to CuO NPs (96-120 hpf) and its impact on zebrafish larvae. Larvae were exposed to commercially available CuO NPs (<50 nm) at various concentrations to obtain the LC50 value (52.556 ppm). Based on the LC50, three groups (10, 20, and 40 ppm) were taken for further analysis. Upon treatment, bradycardia, and impaired swim bladder (reduced/absence of inflation) were found in the treated groups along with alterations in the erythrocyte levels. Also, the angles and distance between the cartilages varied in the treated larvae affecting their craniofacial structures. There was a significant behavior change, as evidenced by the reduced touch escape response and locomotion (speed, distance, time mobile, time frozen, and absolute turn angle). Further, the acetylcholinesterase activity was reduced. Overall, our results suggest that acute exposure to CuO NPs elicits morphological defects in zebrafish larvae.

Evaluation of aversive behavior in Rattus norvegicus experimentally infected by two distinct strains of Toxoplasma gondii (ME49 and VEG): study of epigenetic markers

ABSTRACT Background: Behavioral changes in Rattus norvegicus infected with two strains of Toxoplasma gondii (ME49 and VEG) were investigated. Methods: Rats were evaluated for motor activity and aversion or attraction to cat urine 60 days after infection. After euthanasia, arginine-vasopressin gene methylation in the central nervous system was evaluated. Results: A significant difference was observed in the methylation of the arginine-vasopressin promoter gene between rats infected with the ME49 and VEG strains. Conclusions: Although differences were not observed in many parameters, significant differences were observed in the methylation of the arginine-vasopressin promoter gene in rats infected with the two studied strains.

Un caso de síndrome de crouzon con sintomatología psiquiátrica / A case of Crouzon syndrome with psychiatric symptoms

El síndrome de Crouzon es un trastornoautosómico dominante caracterizado por craneosinostosis (cierre prenatal de una o varias suturas craneales) que provoca alteraciones secundarias de los huesos craneales y de la estructura facial. Las características más frecuentes incluyen deformidadesde cráneo y cara: proptosis ocular, exoftalmos y estrabismo divergente, nariz en forma de pico de loro, labio superior corto, maxilar hipoplásico y prognatismo mandibular relativo. La presión intracraneal enalgunos casos puede producir trastornos neurológicos y discapacidad intelectual.Realizamos una breve revisión del concepto y planteamos un caso clínico quepresenta graves alteraciones de conducta con agresividad y escasa respuesta terapéutica. (AU)

Crouzon syndrome is an autosomal dominant disorder characterized by craniosynostosis (prenatal closure of one or morecranial sutures) that causes secondary alterations of the cranial bones and facial structure. The most frequent features include skull and facial deformities: ocular proptosis, divergent exophthalmos and strabismus,parrot beak-shaped nose, short upper lip, hypoplastic maxilla, and relative mandibular prognathism. Intracranial pressure in some cases can cause neurological disorders andintellectual disability.We carry out a brief review of the concept and we present a clinical case that presents serious behavior alterations with aggressiveness and little therapeutic response. (AU)

Early Long-Term Memory Impairment and Changes in the Expression of Synaptic Plasticity-Associated Genes, in the McGill-R-Thy1-APP Rat Model of Alzheimer's-Like Brain Amyloidosis.

Accruing evidence supports the hypothesis that memory deficits in early Alzheimer Disease (AD) might be due to synaptic failure caused by accumulation of intracellular amyloid beta (Aß) oligomers, then secreted to the extracellular media. Transgenic mouse AD models provide valuable information on AD pathology. However, the failure to translate these findings to humans calls for models that better recapitulate the human pathology. McGill-R-Thy1-APP transgenic (Tg) rat expresses the human amyloid precursor protein (APP751) with the Swedish and Indiana mutations (of familial AD), leading to an AD-like slow-progressing brain amyloid pathology. Therefore, it offers a unique opportunity to investigate learning and memory abilities at early stages of AD, when Aß accumulation is restricted to the intracellular compartment, prior to plaque deposition. Our goal was to further investigate early deficits in memory, particularly long-term memory in McGill-R-Thy1-APP heterozygous (Tg+/-) rats. Short-term- and long-term habituation to an open field were preserved in 3-, 4-, and 6-month-old (Tg+/-). However, long-term memory of inhibitory avoidance to a foot-shock, novel object-recognition and social approaching behavior were seriously impaired in 4-month-old (Tg+/-) male rats, suggesting that they are unable to either consolidate and/or evoke such associative and discriminative memories with aversive, emotional and spatial components. The long-term memory deficits were accompanied by increased transcript levels of genes relevant to synaptic plasticity, learning and memory processing in the hippocampus, such as Grin2b, Dlg4, Camk2b, and Syn1. Our findings indicate that in addition to the previously well-documented deficits in learning and memory, McGill-R-Thy1-APP rats display particular long-term-memory deficits and deep social behavior alterations at pre-plaque early stages of the pathology. This highlights the importance of Aß oligomers and emphasizes the validity of the model to study AD-like early processes, with potentially predictive value.

BEHAVIORAL AND MEMORY CHANGES IN Mus musculus COINFECTED BY Toxocara canis AND Toxoplasma gondii / Alterações comportamentais e na memória de Mus musculus coinfectado por Toxocara canis e Toxoplasma gondii

Several researchers have stated that parasites can alter the behavior of their hosts, in order to increase the transmission rate, principally when prey-predator relationships are a reliable way of infection transmission. The aim of this study was to verify the occurrence of changes in anxiety and short-term memory patterns in experimentally infected Mus musculus by Toxocara canis and/or Toxoplasma gondii. Forty male Mus musculus (Balb/c) eight-week-old were divided into four groups of 10 mice each. One group was infected with 300 eggs of Toxocara canis; a second group was submitted to infection with 10 cysts of Toxoplasma gondii; a third group was concomitantly infected with both parasites with the same inoculums and the last group was maintained without infection. The anxiety levels were evaluated using an elevated plus maze and an actometer; the short-term memory was determined by a two-way active avoidance equipment. The determination of anxiety levels were conducted 40 and 70 days after infection and the short-term memory was evaluated 140 days after infection. Mice chronically infected by Toxoplasma gondii showed impaired learning and short-term memory, but no significant differences were found in mice infected by Toxocara canis or concomitantly infected by Toxocara canis and Toxoplasma gondii when compared to non infected mice.

Pesquisadores afirmam que parasitos podem alterar o comportamento de seus hospedeiros a fim de aumentar a sua taxa de transmissão. O objetivo deste estudo foi verificar a ocorrência de alterações na ansiedade e padrões de memória de curta duração em Mus musculus experimentalmente infectados por Toxocara canis e/ou Toxoplasma gondii. Utilizaram-se 40 camundongos da espécie Mus musculus machos (Balb/c) com oito semanas de idade, divididos em quatro grupos de 10 ratos cada. Um grupo foi infectado com 300 ovos de Toxocara canis, um segundo grupo foi submetido à infecção com 10 cistos de T. gondii, um terceiro grupo foi infectado concomitantemente com ambos os parasitas e o último grupo foi mantido sem infecção. Os níveis de ansiedade foram avaliados por meio de labirinto em cruz elevado e actômetro, a memória de curta duração foi determinada por esquiva aversiva. A determinação dos níveis de ansiedade foi realizada 40 e 70 dias após infecção e a memória de curto prazo foi avaliada 140 dias após a infecção. Camundongos cronicamente infectados por Toxoplasma gondii mostraram deficiência de aprendizagem e memória de curto prazo, mas não foram encontradas diferenças significantes em camundongos infectados por Toxocara canis ou concomitantemente infectados por Toxocara canis e Toxoplasma gondii quando comparados com camundongos não infectados.

An Insight into the Behavior, Course and Kinetics of Acute Infection of Toxoplasma gondii Human RH Strain in Experimentally Infected Murine Model.

BACKGROUND: Toxoplasma gondii, an apicomplexan parasite, is capable of infecting a broad range of intermediate warm-blooded hosts including humans. The parasite seems to be capable of altering the natural behavior of the host to favor its transmission in the environment. The aim of this study was to evaluate the course, alterations in behavior along with normal kinetics of the abnormally induced experimental acute toxoplasmosis in murine models. METHODS: Ten Swiss albino mice were intraperitoneally inoculated with 100 virulent RH strain tachyzoites and finally, the alterations in behavior were described and compared with other known alterations in humans and animals. RESULTS: The behavior and the other symptoms of the acute toxoplasmosis were recorded. Such mice showed typical symptoms like normal coat, severe ascites with pendulous abdomen and tachypnoea exhibited by resting fore legs either on walls of the cage, or nozzle of water bottle or other resting mice and yielded a creamy colored cloudy natured peritoneal fluid on aspiration. CONCLUSIONS: Finally the alterations in behavior were described and compared with other known alterations in humans and animals. The study has generated some important data related to possible causes of behavioral alterations and generation of suitable strategies for control of these alterations in behavior vis-à-vis better understanding of the effect of acute infection of parasite on normal behavior of infected intermediate host.