Hippocampal proteomic changes in high-fat diet-induced obese mice associated with memory decline.

Substantial evidence suggest that chronic consumption of high-fat diets (HFDs) can lead to obesity, abnormal metabolism, as well as cognitive impairment. Molecular and cellular changes regarding hippocampal dysfunctions have been identified in multiple HFD animal models. Therefore, in-depth identification of expression changes of hippocampal proteins is critical for understanding the mechanism of HFD-induced cognitive deficits.

Proteome profiling of the prefrontal cortex of Fmr1 knockout mouse reveals enhancement of complement and coagulation cascades.

Fragile X mental retardation protein (FMRP) deficit resulted from mutations in its encoded fragile X mental retardation 1 (Fmr1) gene is a common inherited cause of Fragile X syndrome (FXS) characterized by intellectual disability and autism spectrum disorder (ASD). The FMRP absence-induced altered gene expression in prefrontal cortex (PFC) are associated with autistic behaviors. However, there lacks a large-scale protein profiling in the PFC upon loss of FMRP.

Lysine acetylome profiling in mouse hippocampus and its alterations upon FMRP deficiency linked to abnormal energy metabolism.

Loss of fragile X retardation protein (FMRP) leads to fragile X syndrome (FXS), a common cause of inherited intellectual disability. Protein lysine acetylation (K-ac), a reversible post-translational modification of proteins, is associated with the regulation of brain development and neuropathies. However, a comprehensive hippocampal K-ac protein profile in response to FMRP deficiency has not been reported until now.

Inhibition of Hypothalamic FTO Activates STAT3 Signal through ERK1/2 Associated with Reductions in Food Intake and Body Weight.

Introduction: Fat mass and obesity-associated (FTO) gene is strongly associated with obesity which brings a major health threat. Altered expression of its encoded protein FTO in the hypothalamus has been identified to contribute to central control of appetite and body weight. However, its molecular mechanisms remain elusive.

High fat suppresses SOD1 activity by reducing copper chaperone for SOD1 associated with neurodegeneration and memory decline.

High fat consumption leads to reactive oxygen species (ROS) which is associated with age-progressive neurological disorders. Cu/Zn superoxide dismutase (SOD1) is a critical enzyme against ROS. However, the relationship between SOD1 and the high-fat-induced ROS and neurodegeneration is poorly known.

The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity.

Aberrant expression or dysfunction of a number of genes in the brain contributes to epilepsy, a common neurological disorder characterized by recurrent seizures. Local overexpression of arachidonate lipoxygenase 3 (ALOXE3), a key enzyme for arachidonic acid (AA) metabolic pathway, alleviates seizure severities. However, the relationship between the ALOXE3 gene mutation and epilepsy has not been reported until now.

Ilepcimide inhibited sodium channel activity in mouse hippocampal neurons.

Ilepcimide (ICM), a clinically effective antiepileptic drug, has been used in China for decades; however, its antiepileptic mechanism remains unclear. ICM is structurally similar to antiepileptic drug lamotrigine (LTG). LTG exerts its anticonvulsant effect by inhibiting voltage-gated Na channel (Na) activity.

Expression Pattern of ALOXE3 in Mouse Brain Suggests Its Relationship with Seizure Susceptibility.

Arachidonic acid (AA), a polyunsaturated fatty acid, is involved in the modulation of neuronal excitability in the brain. Arachidonate lipoxygenase 3 (ALOXE3), a critical enzyme in the AA metabolic pathway, catalyzes the derivate of AA into hepoxilins. However, the expression pattern of ALOXE3 and its role in the brain has not been described until now.

FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight.

Fragile X mental retardation protein (FMRP), strongly associated with fragile X syndrome, plays important roles by regulating gene expression via interacting with other RNA binding proteins in the brain. However, the role of FMRP in hypothalamus, a central part responsible for metabolic control, is poorly known. Our study shows that FMRP is primarily located in the hypothalamic arcuate nucleus (ARC).

Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain.

Valproate (VPA), a widely-used antiepileptic drug, is a selective inhibitor of histone deacetylase (HDAC) that play important roles in epigenetic regulation. The patient with different diseases receiving this drug tend to exhibit weight gain and abnormal metabolic phenotypes, but the underlying mechanisms remain largely unknown. Here we show that VPA increases the Fto mRNA and protein expression in mouse hypothalamic GT1-7 cells.

Hypothalamic proteome changes in response to nicotine and its withdrawal are potentially associated with alteration in body weight.

Nicotine, a major addictive component in tobacco, plays an important role in the changes of body weight upon smoking and its cessation. Here we showed that nicotine-treated mice exhibited weight loss and nicotine withdrawal led to weight gain. Using TMT-based proteomic analysis, we obtained the different hypothalamic protein profiles in response to nicotine and its withdrawal.

Optimization of in silico tools for predicting genetic variants: individualizing for genes with molecular sub-regional stratification.

Genes are unique in functional role and differ in their sensitivities to genetic defects, but with difficulties in pathogenicity prediction. This study attempted to improve the performance of existing in silico algorithms and find a common solution based on individualization strategy. We initiated the individualization with the epilepsy-related SCN1A variants by sub-regional stratification.

A Species-Correlated Transitional Residue D132 on Human FMRP Plays a Role in Nuclear Localization via an RNA-Dependent Interaction With PABP1.

Fragile X mental retardation protein (FMRP), a key determinant of normal brain development and neuronal plasticity, plays critical roles in nucleocytoplasmic shuttling of mRNAs. However, the factors involved in FMRP nuclear localization remain to be determined. Using cross-species sequence comparison, we show that an aspartate in position 132 (D132), located within the conserved nuclear localization signal (NLS) of FMRP, appears in human and other mammals, while glutamate 132 (E132) appears in rodents and birds.

Autapses enhance bursting and coincidence detection in neocortical pyramidal cells.

Autapses are synaptic contacts of a neuron's axon onto its own dendrite and soma. In the neocortex, self-inhibiting autapses in GABAergic interneurons are abundant in number and play critical roles in regulating spike precision and network activity. Here we examine whether the principal glutamatergic pyramidal cells (PCs) also form functional autapses.

Laminar Distribution of Neurochemically-Identified Interneurons and Cellular Co-expression of Molecular Markers in Epileptic Human Cortex.

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups.

Long-term moderate exercise enhances specific proteins that constitute neurotrophin signaling pathway: A TMT-based quantitative proteomic analysis of rat plasma.

Unlabelled: Physical exercise has been reported to increase neurotrophin in brain tissues as hippocampus as well as increased neurotrophic level peripherally in blood plasma and might have an effect on/or affect molecular processes of energy metabolism (and homeostasis). In this study, using quantitative proteomic analysis, we obtained a plasma protein profile from the rat with long-term moderate exercise. A total of 752 proteins were identified in the plasma.

FTO is a transcriptional repressor to auto-regulate its own gene and potentially associated with homeostasis of body weight.

Fat mass and obesity-associated (FTO) protein is a ferrous ion (Fe2+)/2-oxoglutarate (2-OG)-dependent demethylase preferentially catalyzing m6A sites in RNA. The FTO gene is highly expressed in the hypothalamus with fluctuation in response to various nutritional conditions, which is believed to be involved in the control of whole body metabolism. However, the underlying mechanism in response to different nutritional cues remains poorly understood.

MDH2 is an RNA binding protein involved in downregulation of sodium channel Scn1a expression under seizure condition.

Voltage-gated sodium channel α-subunit type I (Na1.1, encoded by SCN1A gene) plays a critical role in the excitability of brain. Downregulation of SCN1A expression is associated with epilepsy, a common neurological disorder characterized by recurrent seizures.

A novel role of fragile X mental retardation protein in pre-mRNA alternative splicing through RNA-binding protein 14.

Fragile X mental retardation protein (FMRP), an important RNA-binding protein responsible for fragile X syndrome, is involved in posttranscriptional control of gene expression that links with brain development and synaptic functions. Here, we reveal a novel role of FMRP in pre-mRNA alternative splicing, a general event of posttranscriptional regulation. Using co-immunoprecipitation and immunofluorescence assays, we identified that FMRP interacts with an alternative-splicing-associated protein RNA-binding protein 14 (RBM14) in a RNA-dependent fashion, and the two proteins partially colocalize in the nuclei of hippocampal neurons.

GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions.

Abnormal expressions of sodium channel SCN1A and SCN3A genes alter neural excitability that are believed to contribute to the pathogenesis of epilepsy, a long-term risk of recurrent seizures. Ketogenic diet (KD), a high-fat and low-carbohydrate treatment for difficult-to-control (refractory) epilepsy in children, has been suggested to reverse gene expression patterns. Here, we reveal a novel role of GAPDH on the posttranscriptional regulation of mouse Scn1a and Scn3a expressions under seizure and KD conditions.

Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway.

Objective: To examine the association between fragile X mental retardation protein (FMRP) expression and astrocytoma characteristics.

Methods: Pathologic grade and expressions of glial fibrillary acidic protein (GFAP), Ki67 (proliferation marker), and FMRP were determined in astrocytoma specimens from 74 patients. Kaplan-Meier survival analysis was undertaken.

Epigenetic Downregulation of Scn3a Expression by Valproate: a Possible Role in Its Anticonvulsant Activity.

Upregulation of sodium channel SCN3A expression in epileptic tissues is known to contribute to enhancing neuronal excitability and the development of epilepsy. Therefore, certain strategies to reduce SCN3A expression may be helpful for seizure control. Here, we reveal a novel role of valproate (VPA) in the epigenetic downregulation of Scn3a expression.

Involvement of FMRP in Primary MicroRNA Processing via Enhancing Drosha Translation.

Fragile X mental retardation protein (FMRP), associated with fragile X syndrome, is known as an RNA-binding protein to regulate gene expression at post-transcriptional level in the brain. FMRP is also involved in microRNA (miRNA) biogenesis during the process of precursor miRNA (pre-miRNA) into mature miRNA. However, there is no description of the effect of FMRP on primary miRNA (pri-miRNA) processing.