Long-term exposure to lead nitrate and zinc sulfate Nile tilapia impact the Aeromonas hydrophila treatment.

BACKGROUND: Pollution with heavy metals (HMs) is time- and concentration-dependent. Lead and zinc pollute the aquatic environment, causing severe health issues in aquatic animals. MATERIALS AND METHODS: Nile tilapia, the predominant cultured fish in Egypt, were experimentally exposed to 10% of LC50 of lead nitrate (PbNO3) and zinc sulfate (ZnSO4). Samples were collected in three different periods, 4, 6, and 8 weeks, in addition to a trial to treat the experimental fish infected with Aeromonas hydrophila, with an antibiotic (florfenicol). RESULTS: Liver enzymes were linearly upsurged in a time-dependent manner in response to HMs exposure. ALT was 92.1 IU/l and AST was 82.53 IU/l after eight weeks. In the eighth week of the HMs exposure, in the hepatic tissue, the levels of glutathione peroxidase (GPx), catalase (CAT), and metallothionein (MT) were increased to 117.8 U/mg prot, 72.2 U/mg prot, and 154.5 U/mg prot, respectively. On exposure to HMs, gene expressions of some cytokines were linearly downregulated in a time-dependent manner compared to the control. After four weeks of exposure to the HMs, the oxidative burst activity (OBA) of immune cells was decreased compared to the control 9.33 and 10.3 cells, respectively. Meanwhile, the serum bactericidal activity (SBA) significantly declined to 18.5% compared to the control 32.6% after eight weeks of exposure. Clinical signs of A. hydrophila infection were exaggerated in polluted fish, with a mortality rate (MR) of 100%. The re-isolation rate of A. hydrophila was decreased in fish treated with florfenicol regardless of the pollution impacts after eight weeks of HMs exposure. CONCLUSION: It could be concluded that the immune suppression and oxidative stress resulting from exposure to HMs are time-dependent. Clinical signs and post-mortem lesions in polluted fish infected with A. hydrophila were prominent. Infected-Nile tilapia had weak responses to florfenicol treatment due to HMs exposure.

Correction: Deficiency of calcium/calmodulin-dependent serine protein kinase disrupts the excitatory-inhibitory balance of synapses by downregulating GluN2B.

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Deficiency of calcium/calmodulin-dependent serine protein kinase disrupts the excitatory-inhibitory balance of synapses by down-regulating GluN2B.

Calcium/calmodulin-dependent serine protein kinase (CASK) is a membrane-associated guanylate kinase (MAGUK) protein that is associated with neurodevelopmental disorders. CASK is thought to have both pre- and postsynaptic functions, but the mechanism and consequences of its functions in the brain have yet to be elucidated, because homozygous CASK-knockout (CASK-KO) mice die before brain maturation. Taking advantage of the X-chromosome inactivation (XCI) mechanism, here we examined the synaptic functions of CASK-KO neurons in acute brain slices of heterozygous CASK-KO female mice. We also analyzed CASK-knockdown (KD) neurons in acute brain slices generated by in utero electroporation. Both CASK-KO and CASK-KD neurons showed a disruption of the excitatory and inhibitory (E/I) balance. We further found that the expression level of the N-methyl-D-aspartate receptor subunit GluN2B was decreased in CASK-KD neurons and that overexpressing GluN2B rescued the disrupted E/I balance in CASK-KD neurons. These results suggest that the down-regulation of GluN2B may be involved in the mechanism of the disruption of synaptic E/I balance in CASK-deficient neurons.

Impacts of dietary zinc oxide nanoparticles on the growth and immunity of Nile tilapia could be ameliorated using Nigella sativa oil.

BACKGROUND: Zinc nanoparticles are documented to be harmful to fish because their accumulation in fish bring about many irreversible changes in their health. Nigella sativa and its oil have been endorsed in aquaculture to improve fish health. METHODS: Two hundred seventy experimental fish (113 ± 5 g body weight) were divided into 6 groups G1-6; control fish fed a diet without any treatment (G1), 0.3% of NSO (G2), 0.5% of NSO (G3), ZnO NPs (40 mg/kg diet) (G4), 0.3% of NSO and ZnO NPs (40 mg/kg diet) (G5), 0.5% of NSO and ZnO NPs (40 mg/kg diet) (G6), the trial lasted for six weeks. RESULTS: Growth performance was enhanced in fish received diets containing NSO, final weight (FW), weight gain (WG), daily weight gain (DWG), and relative growth rate (RGR) were significantly increased with lower food conversion ratios (FCR) compared to the control. The hepatic glutathione peroxidase (GPx), catalase (CAT), and metallothionein (MT) were increased in response to ZnO NPs stress and only 0.5% NSO supplementation could ameliorate such increment. The immune-related genes [interleukin1-beta (IL-1ß), tumor necrosis factor-beta (TNF-ß), transforming growth factor-beta 2 (TGF-ß2) and C-type lysozyme] as well as growth-related gene [insulin-like growth factor 1 (IGF1)] in liver showed an upregulation in fish fed with NSO diets. Administration of ZnO NPs lowered the resistance of Oreochromis niloticus against bacterial infection with Aeromonas hydrophila and NSO could enhance the immunity in the highest tested concentration (0.5%) (G6). CONCLUSIONS: The obtained results implied that NSO could enhance the oxidative and immune status of O. niloticus which could compensate ZnO NPs stress as well as experimental infection of a virulent strain of A. hydrophila. Our results revealed that NSO might increase fish growth and immunity only at a high dose (0.5%).

IQSEC3 Deletion Impairs Fear Memory Through Upregulation of Ribosomal S6K1 Signaling in the Hippocampus.

BACKGROUND: IQSEC3, a gephyrin-binding GABAergic (gamma-aminobutyric acidergic) synapse-specific guanine nucleotide exchange factor, was recently reported to regulate activity-dependent GABAergic synapse maturation, but the underlying signaling mechanisms remain incompletely understood. METHODS: We generated mice with conditional knockout (cKO) of Iqsec3 to examine whether altered synaptic inhibition influences hippocampus-dependent fear memory formation. In addition, electrophysiological recordings, immunohistochemistry, and behavioral assays were used to address our question. RESULTS: We found that Iqsec3-cKO induces a specific reduction in GABAergic synapse density, GABAergic synaptic transmission, and maintenance of long-term potentiation in the hippocampal CA1 region. In addition, Iqsec3-cKO mice exhibited impaired fear memory formation. Strikingly, Iqsec3-cKO caused abnormally enhanced activation of ribosomal P70-S6K1-mediated signaling in the hippocampus but not in the cortex. Furthermore, inhibiting upregulated S6K1 signaling by expressing dominant-negative S6K1 in the hippocampal CA1 of Iqsec3-cKO mice completely rescued impaired fear learning and inhibitory synapse density but not deficits in long-term potentiation maintenance. Finally, upregulated S6K1 signaling was rescued by IQSEC3 wild-type, but not by an ARF-GEF (adenosine diphosphate ribosylation factor-guanine nucleotide exchange factor) inactive IQSEC3 mutant. CONCLUSIONS: Our results suggest that IQSEC3-mediated balanced synaptic inhibition in hippocampal CA1 is critical for the proper formation of hippocampus-dependent fear memory.

Neurexins and neuropsychiatric disorders.

Neurexins are a family of presynaptic single-pass transmembrane proteins that act as synaptic organizers in mammals. The neurexins consist of three genes (NRXN1, NRXN2, and NRXN3), each of which produces a longer α- and shorter ß-form. Genomic alterations in NRXN genes have been identified in a wide variety of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia, intellectual disability (ID), and addiction. Remarkably, a bi-allelic deficiency of NRXN1 was recently linked to Pitt-Hopkins syndrome. The fact that some mono-allelic functional variants of NRXNs are also found in healthy controls indicates that other genetic or environmental factors affect the penetrance of NRXN deficiency. In this review, we summarize the common research methods and representative results of human genetic studies that have implicated NRXN variants in various neuropsychiatric disorders. We also summarize studies of rodent models with NRXN deficiencies that complement our knowledge of human genetics.