Variants of the SH3 and multiple ankyrin repeat domains 3 (SHANK3), which encodes postsynaptic scaffolds, are associated with brain disorders. The targeted alleles in a few Shank3 knock-out (KO) lines contain a neomycin resistance (Neo) cassette, which may perturb the normal expression of neighboring genes; however, this has not been investigated in detail.  https://www.selleckchem.com/products/pomhex.html  We previously reported an unexpected increase in the mRNA expression of Shank3 exons 1-12 in the brains of Shank3B KO mice generated by replacing Shank3 exons 13-16 with the Neo cassette. In this study, we confirmed that the increased Shank3 mRNA in Shank3B KO brains produced an unusual ∼60 kDa Shank3 isoform (Shank3-N), which did not properly localize to the synaptic compartment. Functionally, Shank3-N overexpression altered the dendritic spine morphology in cultured neurons. Importantly, Shank3-N expression in Shank3B KO mice was not a compensatory response to a reduction of full-length Shank3 because expression was still detected in the brain after normalizing the level of full-length Shank3. Moreover, in another Shank3 KO line (Shank3 gKO) with a similar Shank3 exonal deletion as that in Shank3B KO mice but without a Neo cassette, the mRNA expression levels of Shank3 exons 1-12 were lower than those of wild-type mice and Shank3-N was not detected in the brain. In addition, the expression levels of genes neighboring Shank3 on chromosome 15 were altered in the striatum of Shank3B KO but not Shank3 gKO mice. These results suggest that the Neo cassette has potential off-target effects in Shank3B KO mice.Connexins are transmembrane proteins that form hemichannels allowing the exchange of molecules between the extracellular space and the cell interior. Two hemichannels from adjacent cells dock and form a continuous gap junction pore, thereby permitting direct intercellular communication. Connexin 36 (Cx36), expressed primarily in neurons, is involved in the synchronous activity of neurons and may play a role in aberrant synchronous firing, as seen in seizures. To understand the reciprocal interactions between Cx36 and seizure-like neural activity, we examined three questions (a) does Cx36 deficiency affect seizure susceptibility, (b) does seizure-like activity affect Cx36 expression patterns, and (c) does acute blockade of Cx36 conductance increase seizure susceptibility. We utilize the zebrafish pentylenetetrazol [PTZ; a GABA(A) receptor antagonist] induced seizure model, taking advantage of the compact size and optical translucency of the larval zebrafish brain to assess how PTZ affects brain-wide neuronal amefloquine results in increased susceptibility to PTZ-induced neuronal hyperactivity. Together, these results demonstrate a reciprocal relationship between Cx36 and seizure-associated neuronal hyperactivity Cx36 deficiency contributes region-specific susceptibility to neuronal hyperactivity, while neuronal hyperactivity-induced downregulation of Cx36 may increase the risk of future epileptic events.Hepatic encephalopathy (HE) is a neurocognitive dysfunction based on metabolic disorders caused by severe liver disease, which has a high one-year mortality. Mild hepatic encephalopathy (MHE) has a high risk of converting to overt HE, and thus the accurate identification of MHE from cirrhosis with no HE (noHE) is of great significance in reducing mortality. Previously, most studies focused on studying abnormality in the static brain networks of MHE to find biomarkers. In this study, we aimed to use multi-layer modular algorithm to study abnormality in dynamic graph properties of brain network in MHE patients and construct a machine learning model to identify individual MHE from noHE. Here, a time length of 500-second resting-state functional MRI data were collected from 41 healthy subjects, 32 noHE patients and 30 MHE patients. Multi-layer modular algorithm was performed on dynamic brain functional connectivity graph. The connection-stability score was used to characterize the loyalty in each brain network module. Nodal flexibility, cohesion and disjointness were calculated to describe how the node changes the network affiliation across time. Results show that significant differences between MHE and noHE were found merely in nodal disjointness in higher cognitive network modules (ventral attention, fronto-parietal, default mode networks) and these abnormalities were associated with the decline in patients' attention and visual memory function evaluated by Digit Symbol Test. Finally, feature extraction from node disjointness with the support vector machine classifier showed an accuracy of 88.71% in discrimination of MHE from noHE, which was verified by different window sizes, modular partition parameters and machine learning parameters. All these results show that abnormal nodal disjointness in higher cognitive networks during brain network evolution can be seemed as a biomarker for identification of MHE, which help us understand the disease mechanism of MHE at a fine scale.In certain disease states, such as epilepsy, the elevation of blood ketone levels with ketogenic diets (KDs) has beneficial effects, while exogenous ketone supplements (EKSs) were shown to increase the level of blood ketone bodies (such as β-hydroxybutyrate, βHB) and decrease blood glucose levels without dietary restrictions. It has been suggested that ketone body and glucose utilization of the body may be modified by age and gender resulting in changes in blood βHB and glucose levels, but it was not investigated through several months yet. Thus, we investigated whether the effect of an EKS on blood βHB and glucose level is modulated by age and sex in Wistar Albino Glaxo Rijswijk (WAG/Rij) rats, a model animal of human absence epilepsy. We used KEMCT (11 mix of ketone ester/KE and medium-chain triglyceride/MCT oil) by oral gavage in female and male WAG/Rij rats. Animals were fed with standard diet, which was supplemented by KEMCT (2.5 g/kg) once per month by oral gavage for 17 months. One hour after KEMCT tre in female rats at the 17th month than in males. These findings suggest that age and sex can modify the EKS-evoked effects on blood R-βHB and glucose concentrations.