ROS1-mediated decrease in DNA methylation and increase in expression of defense genes and stress response genes in Arabidopsis thaliana due to abiotic stresses.

BACKGROUND: Small interfering RNAs (siRNAs) target homologous genomic DNA sequences for cytosine methylation, known as RNA-directed DNA methylation (RdDM), plays an important role in transposon control and regulation of gene expression in plants. Repressor of silencing 1 (ROS1) can negatively regulate the RdDM pathway. RESULTS: In this paper, we investigated the molecular mechanisms by which an upstream regulator ACD6 in the salicylic acid (SA) defense pathway, an ABA pathway-related gene ACO3, and GSTF14, an endogenous gene of the glutathione S-transferase superfamily, were induced by various abiotic stresses. The results demonstrated that abiotic stresses, including water deficit, cold, and salt stresses, induced demethylation of the repeats in the promoters of ACD6, ACO3, and GSTF14 and transcriptionally activated their expression. Furthermore, our results revealed that ROS1-mediated DNA demethylation plays an important role in the process of transcriptional activation of ACD6 and GSTF14 when Arabidopsis plants are subjected to cold stress. CONCLUSIONS: This study revealed that ROS1 plays an important role in the molecular mechanisms associated with genes involved in defense pathways in response to abiotic stresses.

In vivo stress granule misprocessing evidenced in a FUS knock-in ALS mouse model.

Many RNA-binding proteins, including TDP-43, FUS, and TIA1, are stress granule components, dysfunction of which causes amyotrophic lateral sclerosis (ALS). However, whether a mutant RNA-binding protein disrupts stress granule processing in vivo in pathogenesis is unknown. Here we establish a FUS ALS mutation, p.R521C, knock-in mouse model that carries impaired motor ability and late-onset motor neuron loss. In disease-susceptible neurons, stress induces mislocalization of mutant FUS into stress granules and upregulation of ubiquitin, two hallmarks of disease pathology. Additionally, stress aggravates motor performance decline in the mutant mouse. By using two-photon imaging in TIA1-EGFP transduced animals, we document more intensely TIA1-EGFP-positive granules formed hours but cleared weeks after stress challenge in neurons in the mutant cortex. Moreover, neurons with severe granule misprocessing die days after stress challenge. Therefore, we argue that stress granule misprocessing is pathogenic in ALS, and the model we provide here is sound for further disease mechanistic study.

The Clinical Characteristics and Surgical Treatment of Glossopharyngeal Neuralgia With Pain Radiating to the Innervated Area of the Trigeminal Nerve.

OBJECTIVE: The aim of this study was to investigate the clinical characteristics and surgical outcome of microvascular decompression (MVD) with or without glossopharyngeal nerve and partial vagus nerve rhizotomy for treating glossopharyngeal neuralgia (GPN) patients with pain radiating to the area innervated by the trigeminal nerve. METHODS: A retrospective review was performed to collect the clinical data from GPN patients who had pain in the area innervated by the glossopharyngeal and vagus nerves and radiating to the innervated area of the trigeminal nerve. All patients underwent surgical treatment. The immediate and long-term outcomes were investigated to show the efficacy and safety of the treatment. Information on pain recurrence and complications was collected. RESULTS: Fourteen patients were recruited. The pain area radiated to the trigeminal nerve distribution, including the anterior auricle (57.1%), temple (50%), cheek (28.6%), mandibular gingiva (42.9%), and anterior part of the tongue (14.3%). Swallowing was the most common trigger (85.7%) in these patients. Seven patients underwent MVD of the offending vessel at the root entry zone (REZ) of the glossopharyngeal and vagus nerves. Seven patients underwent MVD plus glossopharyngeal nerve rhizotomy with or without partial vagus nerve rhizotomy. Thirteen patients experienced complete pain relief during the follow-up (mean 49.3 months). CONCLUSIONS: GPN patients with pain radiating to the area innervated by the trigeminal nerve could be successfully treated solely by management of the glossopharyngeal and vagus nerves. In these GPN patients, differential diagnosis is extremely important to identify the true diagnosis, which would reduce the occurrence of iatrogenic injury of the trigeminal nerve during treatment.

Antagomirs Targeting MicroRNA-134 Increase Limk1 Levels After Experimental Seizures in Vitro and in Vivo.

BACKGROUND: MiR-134 is enriched in dendrites of hippocampal neurons and plays crucial roles in the progress of epilepsy. The present study aims to investigate the effects of antagomirs targeting miroRNA-134 (Ant-134) on limk1 expression and the binding of miR-134 and limk1 in experimental seizure. METHODS: Status epilepticus (SE) rat model was established by lithium chloride-pilocarpine injection and was treated with Ant-134 by intracerebroventricular injection. Low Mg2+-exposed primary neurons were used as an in vitro model of SE. The expression of miR-134 was determined using real-time PCR. Protein expressions of limk1 and cofilin were determined by Western blotting. Luciferase reporter assay was used to examine the binding between miR-134 and limk1 3'-untranslated region. RESULTS: The expression of miR-134 was markedly enhanced in hippocampus of the SE rats and low Mg2+-exposed neurons. Ant-134 increased the expression of limk1 and reduced the expression of cofilin in the SE hippocampus and Low Mg2+-exposed neurons. In addition, luciferase reporter assay confirmed that miR-134 bound limk1 3'-UTR. MiR-134 overexpression inhibited limk1 mRNA and protein expressions in neurons. CONCLUSION: Blockage of miR-134 upregulates limk1 expression and downregulated cofilin expression in hippocampus of the SE rats. This mechanism may contribute to the neuroprotective effects of Ant-134.

The ability of anterior thalamic signals to predict seizures in temporal lobe epilepsy in kainate-treated rats.

OBJECTIVE: To analyze the local field potential (LFP) of the anterior nucleus of the thalamus (ANT) of epileptic rats using the Generic Osorio-Frei algorithm (GOFA), and to determine the ability of the ANT LFP to predict clinical seizures in temporal lobe epilepsy. METHODS: GOFA is an advanced real-time technique used to detect and predict seizures. In this article, GOFA was utilized to process the electrical signals of ANT and the motor cortex recorded in 12 rat models of temporal lobe epilepsy (TLE) induced via the injection of kainic acid into the unilateral hippocampus. The electroencephalography (EEG) data included (1) 161 clinical seizures (each contained a 10-min segment) involving the ANT and cortical regions and (2) one hundred three 10-min segments of randomly selected interictal (no seizure) data. RESULTS: Minimal false-positives (0.51 ± 0.36/h) and no false-negatives were detected based on the ANT LFP data processed using GOFA. In ANT LFP, the delay from electrographic onset (EO) to automated onset (AO) was 1.24 ± 0.47 s, and the delay from AO to clinical onset (CO) was 7.73 ± 3.23 s. The AO time occurred significantly earlier in the ANT than in the cortex (p = 0.001). In 75.2% of the clinical onsets predicted by ANT LFP, it was 1.37 ± 0.82 s ahead of the prediction of cortical potentials (CPs), and the remainder were 0.84 ± 0.31 s slower than the prediction of CPs. SIGNIFICANCE: ANT LFP appears to be an optimal option for the prediction of seizures in temporal lobe epilepsy. It was possible to upgrade the responsive neurostimulation system to emit electrical stimulation in response to the prediction of epileptic seizures based on the changes in the ANT LFP.

Automated Segmentation and Reconstruction of the Subthalamic Nucleus in Parkinson's Disease Patients.

OBJECTIVE: In the treatment of Parkinson's disease for deep brain stimulation (DBS), the subthalamic nucleus (STN) is the most important target on a specific brain nucleus. Although procedural details are well established, targeting STN remains problematic because of its variable location and relatively small size. MATERIALS AND METHODS: Data were collected from 10 patients with Parkinson's disease implanted with deep brain stimulation devices. This paper presents an automated algorithm for 3.0T magnetic resonance (MR) image segmentation using the level set method to reconstruct the STN based on automatic segmentation. Implicit polynomial surfaces are used for the reconstruction of the STN segmentation. RESULTS: The method was applied to 10 Parkinson's disease (PD) patients to automatically extract and rebuild the STN. A comparison of the Euclidean distances and dice overlap coefficient showed no significant differences with the segmentation-based method, with the present method having smaller prediction errors and being more robust than expert systems. CONCLUSIONS: This paper presents an automated algorithm to segment and reconstruct the small human STN using MR images. This method for STN should provide an effective method for advancing STN localization and direct visualization.

NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model.

BACKGROUND: Temporal lobe epilepsy (TLE) is often characterized pathologically by severe neuronal loss in the hippocampus. Understanding the mechanisms of neuron death is key to preventing the neurodegeneration associated with TLE. However, the involvement of neuronal loss to the epileptogenic process has yet to be fully determined. Recent studies have shown that the activation of NLRP1 can generate a functional caspase-1-containing inflammasome in vivo to drive the proinflammatory programmed cell death termed 'pyroptosis', which has a key role in the pathogenesis of neurological disorders. To the best of our knowledge, there are no reported studies that performed detailed identification and validation of NLRP1 inflammasome during the epileptogenic process. METHODS: We first compared expression of NLRP1 and caspase-1 in resected hippocampus from patients with intractable mesial temporal lobe epilepsy (mTLE) with that of matched control samples. To further examine whether the activation of NLRP1 inflammasome contributes to neuronal pyroptosis, we employed a nonviral strategy to knock down the expression of NLRP1 and caspase-1 in the amygdala kindling-induced rat model. Proinflammatory cytokines levels and hippocampal neuronal loss were evaluated after 6 weeks of treatment in these NLRP1 or caspase-1 deficiency TLE rats. RESULTS: Western blotting detected upregulated NLRP1 levels and active caspase-1 in mTLE patients in comparison to those levels seen in the controls, suggesting a role for this inflammasome in mTLE. Moreover, we employed direct in vivo infusion of nonviral small interfering RNA to knockdown NLRP1 or caspase-1 in the amygdala kindling-induced rat model, and discovered that these NLRP1 or caspase-1 silencing rats resulted in significantly reduced neuronal pyroptosis. CONCLUSIONS: Our data suggest that NLRP1/caspase-1 signaling participates in the seizure-induced degenerative process in humans and in the animal model of TLE and points to the silencing of NLRP1 inflammasome as a promising strategy for TLE therapy.

Application of AI in biological age prediction.

The development of anti-aging interventions requires quantitative measurement of biological age. Machine learning models, known as "aging clocks," are built by leveraging diverse aging biomarkers that vary across lifespan to predict biological age. In addition to traditional aging clocks harnessing epigenetic signatures derived from bulk samples, emerging technologies allow the biological age estimating at single-cell level to dissect cellular diversity in aging tissues. Moreover, imaging-based aging clocks are increasingly employed with the advantage of non-invasive measurement, making it suitable for large-scale human cohort studies. To fully capture the features in the ever-growing multi-modal and high-dimensional aging-related data and uncover disease associations, deep-learning based approaches, which are effective to learn complex and non-linear relationships without relying on pre-defined features, are increasingly applied. The use of big data and AI-based aging clocks has achieved high accuracy, interpretability and generalizability, guiding clinical applications to delay age-related diseases and extend healthy lifespans.

Surgical management of nervus intermedius neuralgia: A report of 4 cases and literature review.

BACKGROUND: Nervus intermedius neuralgia (NIN) is characterized by paroxysmal episodes of sharp, lancinating pain in the deep ear. Unfortunately, only a few studies exist in the literature on this pain syndrome, its pathology and postoperative outcomes. METHOD: We conducted a retrospective review of four cases diagnosed with NIN who underwent a neurosurgical intervention at our center from January 2015 to January 2023. Detailed information on their MRI examinations, intraoperative findings and other clinical presentations were obtained, and the glossopharyngeal and vagus nerves were isolated for immunohistochemistry examination. RESULTS: A total of 4 NIN patients who underwent a microsurgical intervention at our institution were included in this report. The NI was sectioned in all patients and 3 of them underwent a microvascular decompression. Of these 4 patients, 1 had a concomitant trigeminal neuralgia (TN), and 1 a concomitant glossopharyngeal neuralgia (GPN). Three patients underwent treatment for TN and 2 for GPN. Follow-up assessments ranged from 8 to 99 months. Three patients reported complete pain relief immediately after the surgery until last follow-up, while in the remaining patient the preoperative pain gradually resolved over the 3 month period. Immunohistochemistry revealed that a greater amount of CD4+ and CD8+ T cells had infiltrated the glossopharyngeal versus vagus nerve. CONCLUSIONS: NIN is an extremely rare condition showing a high degree of overlap with TN/GPN. An in depth neurosurgical intervention is effective to completely relieve NIN pain, without any serious complications. It appears that T cells may play regulatory role in the pathophysiology of CN neuralgia.

A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration.

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.

[Changes of glutamate and γ-aminobutyric acid of extracellular fluid in hippocampus during electrical stimulation of anterior nucleus thalamus in rats].

OBJECTIVE: To explore the changes of extracellular glutamate (Glu) and γ-aminobutyric acid (GABA) in hippocampus during the high-frequency stimulation of anterior nucleus thalamus (ANT) in epileptic rats. METHODS: A total of 30 rats were divided equally into 2 groups:epilepsy model and normal control (n = 15 each). Concentric bipolar electrodes were stereotaxically implanted in bilateral ANT. A high-frequency stimulation of 130 Hz was applied in the epilepsy group. Microdialysis probes were unilaterally lowered into hippocampus. The concentrations of Glu and GABA in dialysate samples were determined by high-performance liquid chromatography (HPLC). RESULTS: Electrical stimulation of ANT induced an increase of GABA and a decrease of Glu in hippocampus. CONCLUSION: An increase of GABA and a decrease of Glu during the electrical stimulation of ANT play an important role in the therapy of epilepsy.

Dual-gRNA approach with limited off-target effect corrects C9ORF72 repeat expansion in vivo.

C9ORF72 GGGGCC repeat expansion is the most common genetic cause for amyotrophic lateral sclerosis and frontotemporal dementia, which generates abnormal DNA and RNA structures and produces toxic proteins. Recently, efficacy of CRISPR/Cas9-mediated editing has been proven in treatment of disease. However, DNA low complexity surrounding C9ORF72 expansion increases the off-target risks. Here we provide a dual-gRNA design outside of the low complexity region which enables us to remove the repeat DNA in a 'cutting-deletion-fusion' manner with a high fusion efficiency (50%). Our dual-gRNA design limits off-target effect and does not significantly affect C9ORF72 expression. In neurons carrying patient C9ORF72 expansion, our approach removes the repeat DNA and corrects the RNA foci in vitro and in vivo. Therefore, we conclude that our proof-of-concept design correct C9ORF72 repeat expansion, which may have potential therapeutic value for the patients.

Comparation of the structural characteristics and biological activities of chondroitin sulfates extracted from notochord and backbone of Chinese sturgeon (Acipenser sinensis).

To compare the structural properties and biological activities of chondroitin sulfate (CS) in two different tissues of Chinese sturgeon (Acipenser sinensis) and Russian sturgeon (Acipenser gueldenstaedti), we extracted their backbone cartilage CS (Cart-CS) and notochord CS (Noto-CS), and analyzed the CS structural properties using chromatographic and spectroscopic methods. The molecular weights of Chinese sturgeon Cart-CS and Noto-CS were 54.7 and 25.4 kDa, respectively, and the molecular weights of Russian sturgeon were 50.0 and 38.4 kDa, respectively. The disaccharide composition results showed that Cart-CS was mainly composed of CS-C, while Noto-CS was almost composed of pure CS-A. The antioxidant activity of sturgeon CS and its effect on collagen fibril formation were discussed. Sturgeon CS exhibited higher antioxidant activity than shark and bovine CSs. Sturgeon CS inhibited the self-assemble of type I collagen into fibrils. The inhibition effect of Cart-CS was higher than that of Noto-CS. The high value-added utilization of Cart-CS and Noto-CS will increase the value of sturgeon by-products. Furthermore, the disaccharide composition of CS in sturgeon depends on tissues of origin, but not on species. It means that the CS of Chinese sturgeon can be substituted by the CS of other commercial sturgeon. That will contribute to the protection of endangered species of Chinese sturgeon from illegal fishing and increase the value of commercial sturgeon by-products.

Optimizing the Optical Absorption of Poly(heptazine imide) by the n → π* Electron Transition for Improved Photocatalytic H2 Evolution.

Poly(heptazine imide) (abbreviated as PHI), a heptazine-based crystalline carbon nitride photocatalyst, has attracted widespread attention in the photocatalytic H2 evolution benefiting from its high crystallinity. Nevertheless, the optical absorption range of the directly synthesized PHI is generally narrow, which severely hinders the utilization of visible light. Much research aimed to extend the optical absorption range of PHI; however, either the optimization degree was insufficient or the synthesis process was cumbersome. Herein, red PHI (RPHI) for improving the photocatalytic H2 evolution was facilely synthesized by the one step method. The optimal RPHI sample possesses an obvious new absorption band of the n → π* electron transition and exhibits a significantly enhanced photocatalytic H2 evolution rate of 169 µmol h-1 (λ > 510 nm) and 46 µmol h-1 (λ > 600 nm), which is about 5 times (λ > 510 nm) and 7.7 times (λ > 600 nm) that of pristine PHI and surpasses most reported RPHIs. This work may promote the development of the PHI photocatalyst for near-infrared photocatalytic H2 production.

Effects of phosphate ion concentration on in-vitro fibrillogenesis of sturgeon type I collagen.

Nonmammalian collagens have attracted significant attention owing to their potential for use as a source of cell scaffolds for tissue engineering. Since the morphology of collagen fibrils controls cell proliferation and differentiation, its regulation is essential for fabricating scaffolds with desirable characteristics. In this study, we evaluated the effects of the phosphate ion (Pi) concentration on the characteristics of fibrils formed from swim bladder type I collagen (SBC) and skin type I collagen (SC) from the Bester sturgeon. An increase in the Pi concentration decreased the fibril formation rate, promoted the formation of thick fibrils, and increased the thermal stability of the fibrils for both SBC and SC. However, the SBC and SC fibrils exhibited different fibril formation rates, degrees of fibrillogenesis, morphologies, and denaturation temperatures for the same reaction conditions. Finally, by regulating the Pi concentration, various types of SBC and SC fibrils could be coated on cell culture wells, and fibroblasts could be cultured on them. The results showed that thin fibrils enhance fibroblast extension and proliferation, whereas thick fibrils restrain fibroblast extension but orient them in the same direction. The results of this study suggest that SBC fibrils, which exhibit diverse morphologies, are suitable for use as a novel scaffold material, whose characteristics can be tailored readily by varying the Pi concentration.

The viral suppressor HCPro decreases DNA methylation and activates auxin biosynthesis genes.

Auxin has profound effects on plant growth and development. In addition to participating in plant growth and development, the auxin signaling pathway is involved in plant defense against pathogens. In this study, we investigated the molecular mechanism by which helper-component protease (HCPro) encoded by the Tobacco vein banding mosaic virus (TVBMV) activates auxin biosynthesis genes (YUCs) and interferes with the auxin signaling pathway. Our results demonstrated that the viral suppressor HCPro decreased the DNA methylation of dispersed repeats (DRs) within the promoters of YUC1, YUC5 and YUC10 and transcriptional activated these YUC genes targeted by RNA-directed DNA methylation (RdDM), leading to an increase in auxin accumulation in plants. Furthermore, we found that the induction of these YUCs by HCPro was attenuated in ros1 mutant plants, suggesting that HCPro-mediated transcriptional activation of the genes was partly dependent on ROS1-mediated DNA demethylation.

N-terminal truncated carboxypeptidase E represses E-cadherin expression in lung cancer by stabilizing the Snail-HDAC complex.

The N-terminal truncated carboxypeptidase E (CPEΔN) protein, an alternative splicing product of the carboxypeptidase E gene, has recently been recognized as an independent predictor for the recurrence and metastasis of lung adenocarcinoma. In this study, we showed that CPEΔN may accelerate lung cancer invasion via an E-cadherin-dependent mechanism. In vitro experiments and in vivo bioluminescence imaging assay revealed CPEΔN promoted the mobility and invasion of human lung cancer cells by suppressing endogenous expression of E-cadherin, a critical regulator for epithelial tissue homeostasis. Further mechanistic analyses revealed that CPEΔN directly interacted with and stabilized the Snail/HDAC1/HDAC3 complex within the promoter region of the E-cadherin-encoding CDH1 gene. CPEΔN overexpression led to a reduction of histone H3K9 acetylation and an increase of H3K9 and H3K27 trimethylation in the CHD1 gene promoter and ultimately inhibited E-cadherin transcription. In addition, correlations among CPEΔN, E-cadherin expression and tumor progression in 195 cases of lung adenocarcinoma patients were analyzed. Higher nuclear expression of CPEΔN was detected in patients with advanced stage of lung adenocarcinoma. Nuclear expression of CPEΔN was negatively correlated with the cell membrane expression of E-cadherin. Collectively, our findings illustrated that CPEΔN was involved in the transcriptional regulation of the epithelial-mesenchymal transition-related gene CDH1 and provide novel insights into CPEΔN-associated lung cancer metastasis.

The effect of alkaline pretreatment on the biochemical characteristics and fibril-forming abilities of types I and II collagen extracted from bester sturgeon by-products.

Non-mammalian collagens have attracted increasing attention for industrial and biomedical use. We have therefore evaluated extraction conditions and the biochemical properties of collagens from aquacultured sturgeon. Pepsin-soluble type I and type II collagen were respectively extracted from the skin and notochord of bester sturgeon by-products, with yields of 63.9 ±â€¯0.19% and 35.5 ±â€¯0.68%. Collagen extraction efficiency was improved by an alkaline pretreatment of the skin and notochord (fewer extraction cycles were required), but the final yields decreased to 56.2 ±â€¯0.84% for type I and 31.8 ±â€¯1.13% for type II. Alkaline pretreatment did not affect the thermal stability or triple-helical structure of both types of collagen. Types I and II collagen formed re-assembled fibril structures in vitro, under different conditions. Alkaline pretreatment slowed down the formation of type I collagen fibrils and specifically inhibited the formation of thick fibril-bundle structures. In contrast, alkaline pretreatment did not change type II collagen fibril formation. In conclusion, alkaline pretreatment of sturgeon skin and notochord is an effective method to accelerate collagen extraction process of types I and II collagen without changing their biochemical properties. However, it decreases the yield of both collagens and specifically changes the fibril-forming ability of type I collagen.

Silencing MicroRNA-134 Alleviates Hippocampal Damage and Occurrence of Spontaneous Seizures After Intraventricular Kainic Acid-Induced Status Epilepticus in Rats.

Epilepsy is a disorder of abnormal brain activity typified by spontaneous and recurrent seizures. MicroRNAs (miRNAs) are short non-coding RNAs, critical for the post-transcriptional regulation of gene expression. MiRNA dysregulation has previously been implicated in the induction of epilepsy. In this study, we examined the effect of silencing miR-134 against status epilepticus (SE). Our results showed that level of miR-134 was significantly up-regulated in rat brain after Kainic acid (KA)-induced SE. TUNEL staining showed that silencing miR-134 alleviated seizure-induced neuronal apoptosis in the CA3 subfield of the hippocampus. Western blot showed that a miR-134 antagonist suppressed lesion-induced endoplasmic reticulum (ER) stress and apoptosis related expression of CHOP, Bim and Cytochrome C, while facilitated the expression of CREB at 24 h post KA-induced lesion in the hippocampus. Consistently, silencing miR-134 significantly diminished loss of CA3 pyramidal neurons using Nissl staining as well as reducing aberrant mossy fiber sprouting (MFS) in a rat epileptic model. In addition, the results of EEG and behavior analyses showed seizures were alleviated by miR-134 antagonist in our experimental models. These results suggest that silencing miR-134 modulates the epileptic phenotype by upregulating its target gene, CREB. This in turn attenuates oxidative and ER stress, inhibits apoptosis, and decreases MFS long term. This indicates that silencing miR-134 might be a promising intervention for the treatment of epilepsy.

Anterior nucleus of thalamus stimulation inhibited abnormal mossy fiber sprouting in kainic acid-induced epileptic rats.

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has demonstrated antiepileptic efficacy, especially for mesial temporal lobe epilepsy (MTLE). Mossy fiber sprouting (MFS) is involved in the pathogenesis of MTLE, and Sema-3A and GAP-43 are pivotal regulators of MFS. This study investigated the effects of ANT-DBS on MFS and expression levels of Sema-3A and GAP-43 as a possible mechanism for seizure suppression. METHODS: Adult male Sprague-Dawley rats were randomly divided into four groups: (1) control (saline injection), (2) KA (kainic acid injection), (3) KA + Sham-DBS (electrode implantation without stimulation), and (4) KA + DBS (electrode implantation with stimulation). Video electroencephalography (EEG) was used to ensure model establishment and monitor seizure frequency, latency, and severity (Racine stage). Chronic ANT stimulation was conducted for 35 days in the KA + DBS group, and MFS compared to the other groups by quantitative Timm staining. Sema-3A and GAP-43 expression levels in the hippocampal formation were evaluated in all groups with western blot. RESULTS: The latency period was significantly prolonged and spontaneous seizure frequency reduced in the KA + DBS group compared to KA and KA + Sham-DBS groups. Staining scores for MFS in CA3 and dentate gyrus (DG) were significantly lower in the KA + DBS group. The KA + DBS group also exhibited decreased GAP-43 expression and increased Sema-3A expression compared to KA and KA + Sham-DBS groups. CONCLUSION: These results suggest that ANT-DBS extends the latent period following epileptogenic stimulation by impeding MFS through modulation of GAP-43 and Sema-3A expression.