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Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with a Brazilian ZIKV isolate and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed that in utero infection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline.Summary StatementZika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

Zika virus is an arthropod-borne flavivirus mainly transmitted by the bite of infected mosquitoes. However, alternative transmission routes can occur. In this study, we show the accidental transmission of virus from an infected mouse to a human during the experimental manipulation. This study describes the patient clinical manifestations and virus genome identification., We describe a new route of transmission of Zika virus from an infected mouse to human during experimental manipulation.

Viral infections in early pregnancy are a major cause of microcephaly. However, how distinct viruses impair human brain development remains poorly understood. Here we use human brain organoids to study the mechanisms underlying microcephaly caused by Zika Virus (ZIKV) and Herpes Simplex Virus (HSV-1). We find that both viruses efficiently replicate in brain organoids and attenuate their growth by causing cell death. However, transcriptional profiling reveals that ZIKV and HSV-1 elicit distinct cellular responses and HSV-1 uniquely impairs neuroepithelial identity. Furthermore, we demonstrate that while both viruses fail to potently induce the type I interferon system, the organoid defects caused by their infection can be rescued by distinct type I interferons. These phenotypes are not seen in 2D cultures, highlighting the superiority of brain organoids in modeling viral infections. Together, these results uncover virus-specific mechanisms and complex cellular immune defenses associated with virus-induced microcephaly.

Chronic exposure to paraquat (Pq), a toxic herbicide, can result in Parkinsonian symptoms. This study evaluated the effect of the systemic administration of Pq on locomotion, learning and memory, social interaction, tyrosine hydroxylase (TH) expression, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, and dopamine transporter (DAT) gene expression in zebrafish. Adult zebrafish received an i.p. injection of either 10 mg/kg (Pq10) or 20 mg/kg (Pq20) of Pq every 3 days for a total of six injections. Locomotion and distance traveled decreased at 24 h after each injection in both treatment doses. In addition, both Pq10- and Pq20-treated animals exhibited differential effects on the absolute turn angle. Nonmotor behaviors were also evaluated, and no changes were observed in anxiety-related behaviors or social interactions in Pq-treated zebrafish. However, Pq-treated animals demonstrated impaired acquisition and consolidation of spatial memory in the Y-maze task. Interestingly, dopamine levels increased while DOPAC levels decreased in the zebrafish brain after both treatments. However, DAT expression decreased in the Pq10-treated group, and there was no change in the Pq20-treated group. The amount of TH protein showed no significant difference in the treated group. Our study establishes a new model to study Parkinson-associated symptoms in zebrafish that have been chronically treated with Pq.

The interest in the behavioral features of zebrafish has significantly increased over the past two decades. However, most available protocols have used longer training periods and have been based on reinforcement/reward or avoidance. The Y-Maze memory task has the advantage of using a simple and rapid training session, but it has not been established in zebrafish. Here, we have characterized this task for zebrafish, with the addition of pharmacological interventions in the acquisition and consolidation memory phases. The results show that zebrafish spend more time in the novel arm than in the other arms of the Y-Maze, both in response to novelty and spatial memory training-test intervals (TTIs). We have also studied the involvement of the glutamatergic and cholinergic systems with pre- and post-training treatments with the NMDA receptor antagonist MK-801 (20 μM) and the cholinergic blocker scopolamine (200 μM). After 1h of TTI, pre-training MK-801 and scopolamine-treated fish reduced their exploration of the novel arm when compared to the control group, with no changes in their locomotor activity. Post-training of MK-801 treatment also impaired their Y-Maze performance, while post-training of any scopolamine treatment failed to affect novel arm exploration. In conclusion, the Y-Maze memory task can be reliably used for zebrafish, providing a new, rapid, and preference/avoidance independent task for the study of memory in this teleost. In addition, our results highlight the implication of the glutamatergic and cholinergic systems in the memory of zebrafish.