Background: Epilepsy is a widespread and chronic disease of the central nervous system caused by a variety of factors. Mitochondrial ferritin (FtMt) refers to ferritin located within the mitochondria that may protect neurons against oxidative stress by binding excess free iron ions in the cytoplasm. However, the potential role of FtMt in epilepsy remains unclear. We aimed to investigate whether FtMt and its related mechanisms can regulate epilepsy by modulating ferroptosis.Methods: Three weeks after injection of adeno‐associated virus (AAV) in the skull of adult male C57BL/6 mice, kainic acid (KA) was injected into the hippocampus to induce seizures. Primary hippocampal neurons were transfected with siRNA using a glutamate‐mediated epilepsy model. After specific treatments, Western blot analysis, immunofluorescence, EEG recording, transmission electron microscopy, iron staining, silver staining, and Nissl staining were performed.Results: At different time points after KA injection, the expression of FtMt protein in the hippocampus of mice showed varying degrees of increase. Knockdown of the FtMt gene by AAV resulted in an increase in intracellular free iron levels and a decrease in the function of iron transport‐related proteins, promoting neuronal ferroptosis and exacerbating epileptic brain activity in the hippocampus of seizure mice. Additionally, increasing the expression level of FtMt protein was achieved by AAV‐mediated upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) gene in the hippocampus of seizure mice.Conclusions: In epilepsy, Nrf2 modulates ferroptosis by involving the expression of FtMt and may be a potential therapeutic mechanism of neuronal injury after epilepsy. Targeting this relevant process for treatment may be a therapeutic strategy to prevent epilepsy.

Potassium channels (K⁺) play an important role in the regulation of cellular signaling. Dysfunction of potassium channels is associated with several severe ion channels diseases, such as long QT syndrome, episodic ataxia and epilepsy. Ultrasound stimulation has proven to be an effective non-invasive tool for the modulation of ion channels and neural activity. In this study, we demonstrate that ultrasound stimulation enables to modulate the potassium currents and has an impact on the shape modulation of action potentials (AP) in the hippocampal pyramidal neurons using whole-cell patch-clamp recordings in vitro. The results show that outward potassium currents in neurons increase significantly, approximately 13%, in response to 30 s ultrasound stimulation. Simultaneously, the increasing outward potassium currents directly decrease the resting membrane potential (RMP) from −64.67 ± 1.10 mV to −67.51 ± 1.35 mV. Moreover, the threshold current and AP fall rate increase while the reduction of AP half-width and after-hyperpolarization peak time is detected. During ultrasound stimulation, reduction of the membrane input resistance of pyramidal neurons can be found and shorter membrane time constant is achieved. Additionally, we verify that the regulation of potassium currents and shape of action potential is mainly due to the mechanical effects induced by ultrasound. Therefore, ultrasound stimulation may offer an alternative tool to treat some ion channels diseases related to potassium channels.

Rationale: The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI.

Neuroinflammation is considered to be a significant mechanism contributing to depression. Several studies have reported that A1 astrocytes were highly prevalent in human neuroinflammatory and neurodegenerative diseases. However, the precise mechanism by which A1 astrocytes contribute to depression remains unclear. Clinical studies have suggested a correlation between TNF-α, an activator of A1 astrocytes, and the severity of depression. Based on these findings, we hypothesized that TNF-α might worsen depression by activating A1 astrocytes. Our previous studies indicated that Rhodomyrtone (Rho) has the potential to improve depression-like behavior in mice. However, the exact mechanism for this effect has not been fully elucidated. Importantly, it was reported that Rho alleviated skin inflammation in a mouse model of psoriasis by inhibiting the expression of TNF-α. Based on this finding, we hypothesized that rhodomyrtone may exert antidepressant effects by modulating the TNF-α pathway. However, further research is required to investigate and validate these hypotheses, shedding light on the relationships between neuroinflammation, A1 astrocytes, TNF-α, and depression. By obtaining a deeper understanding of the underlying mechanisms, these findings could lead to the development of novel antidepressant strategies that target the TNF-α pathway in the context of neuroinflammation. In vivo, based on the established chronic unpredictable mild stress (CUMS) mouse depression model, we characterized the mechanism of TNF-α and Rho during depression by using several behavioral assays, adeno-associated virus(AAV) transfection, western blotting, immunofluorescence, and other experimental methods. In vitro, we characterized the effect of Rho on inflammation in TNF-α-treated primary astrocytes. TNFR1 expression was significantly increased in the hippocampus of depression-like mice, with increased astrocytes activation and neuronal apoptosis. These processes were further enhanced with increasing levels of TNF-α in the cerebrospinal fluid of mice. However, this process was attenuated by knockdown of TNFR1 and infliximab (Inf; a TNF-α antagonist). Injection of rhodomyrtone decreased the expressions of TNFR1 and TNF-α, resulting in significant improvements in mouse depression-like behaviors and reduction of astrocyte activation. TNF-α could be involved in the pathophysiological process of depression, through mediating astrocytes activation by binding to TNFR1. By blocking this pathway, Rho may be a novel antidepressant.

The pathogenesis of Parkinson’s disease remains unclear that there is no cure for Parkinson’s disease yet. The abnormal expressions of certain miRNA are closely related to the occurrence and progression of Parkinson’s disease. Here, we demonstrate that miR‐9‐5p inhibits the dopaminergic neuron apoptosis via the regulation of β‐catenin signaling which directly targets SCRIB, a tumor suppressor gene. Besides, miR‐9‐5p improved the motor function of mice with Parkinson’s disease. The results of this study suggest that miR‐9‐5p might be a potential therapeutic target against Parkinson’s disease.