Anti-NLGN1 (phospho T739) polyclonal antibody

Mepanipyrim is a widely used fungicide, and residues of mepanipyrim are frequently detected in commodities. However, the neurotoxicity and underlying mechanisms of mepanipyrim are still insufficiently understood. In this study, zebrafish embryos at 0.5-1.0 post-fertilization hours (hpf) were exposed to 0.1, 1, 10 and 100 mu g/L mepanipyrim for 7 days. Our results showed that mepanipyrim could cause the locomotor hyperactivity and increase the concentration of gamma-amino butyric acid (GABA) and the Na+/K+- and Ca2+-ATPase activities in zebrafish larvae. We have conducted the RNA-sequence and RT-qPCR to analyze the gene expressions. The mRNA expression levels of calcium/sodium ion conduction associated genes were observably up-regulated, demonstrating that mepanipyrim could enhance the cell energy metabolism, the synaptic transmission and skeletal muscle contraction, which were consistent with the locomotor hyperactivity. Meanwhile, exposure to mepanipyrim could significantly change the gene expression levels of gad1, bdnf, nlgn1, and type A and B GABA receptors in zebrafish larvae. This is the first study focusing on the underlying mechanisms of the neurotoxic effects that are induced by mepanipyrim. (C) 2020 Elsevier Ltd. All rights reserved.

Synapse loss occurs early and correlates with cognitive decline in Alzheimer's disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (A beta o), but the exact synaptic components targeted by A beta o remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by A beta o, and that it can modulate A beta o toxicity. We found that hippocampal NLGN1 was decreased in patients with AD in comparison to patients with mild cognitive impairment and control subjects. Female 3xTg-AD mice also showed a decreased NLGN1 level in the hippocampus at an early age (i.e., 4 months). We observed that chronic hippocampal A beta o injections initially increased the expression of one specific Nlgn1 transcript, which was followed by a clear decrease. Lastly, the absence of NLGN1 decreased neuronal counts in the dentate gyrus, which was not the case in wild-type animals, and worsens impairment in spatial learning following chronic hippocampal A beta o injections. Our findings support that NLGN1 is impacted early during neurodegenerative processes, and that A beta o contributes to this effect. Moreover, our results suggest that the presence of NLGN1 favors the cognitive prognosis during A beta o-driven neurodegeneration.