MiR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models (pentylenetetrazole- and pilocarpine-induced seizures), while miR-124 inhibitor led to shortened onset latency in pilocarpine-induced seizure rat models. Moreover, the result of local field potentials (LFPs) records further demonstrated miR-124 may have anti-epilepsy function. Inhibition of neuronal firing by miR-124 was associated with the suppression of mEPSC, AMPAR- and NMDAR-mediated currents, which were accompanied by decreased surface expression of NMDAR. In addition, miR-124 injection resulted in decreased activity and expression of cAMP-response element-binding protein1 (CREB1). a key regulator in epileptogenesis. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3′UTR of CREB1 gene and repressed the CREB1 expression in HEK293T cells. Immunoprecipitation studies confirmed that the CREB1 antibody effectively precipitated CREB1 and NMDAR1 but not GLUR1 from rat brain hippocampus. These results revealed a previously unknown function of miR-124 in neuronal excitability and provided a new insight into molecular mechanisms underlying epilepsy.

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1^G93A or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. For the first time, we observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1^G93A mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1^G93A mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1^G93A mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.

Acute intermittent porphyria (AIP) is an inherited metabolic disorder that can affect the central, peripheral, and autonomic nervous systems. Therefore, its clinical presentation is diverse and may include abdominal pain, as well as neurological and psychiatric symptoms. Abdominal pain, though a common initial symptom, is often overlooked or misdiagnosed due to its lack of specificity. But early diagnosis and treatment are crucial, as untreated symptoms can progressively worsen. This report describes a 26-year-old male who was admitted due to seizures and PRES changes on brain magnetic resonance imaging (MRI) for over 30 days, along with a 20-day history of sudden proximal weakness in both upper limbs. Additionally, he experienced recurrent vomiting and excessive sweating. Five months before admission, he was diagnosed with a urinary tract infection due to severe abdominal pain and tea-colored urine, and the symptoms resolved after treatment. Multiple examinations before and after admission consistently revealed hypertension, tachycardia, and hyponatremia. Electromyography (EMG) suggested axonal damage to the motor nerves of both upper limbs. During hospitalization, the patient's upper limb weakness progressively worsened, and around 12 days after admission, he began experiencing recurrent episodes of abdominal pain and limb pain. Then he was diagnosed with AIP based on the detection of positive PBG in urin and the identification of a c.445C > T (R149X) mutation in the hydroxymethylbilane synthase (HMBS) gene. This case unveils that AIP is a disease that can be easily overlooked in its early stages. When a patient presents with central, peripheral, or autonomic nervous system symptoms and common causes are ruled out, AIP should be considered as a potential diagnosis. Additionally, unexplained symptoms such as abdominal pain, changes in urine color, hyponatremia should also raise suspicion. Timely screening through biochemical testing, including measurement of ALA, PBG and porphyrins in a random urine sample, is recommended. Timely administration of intravenous hemin and avoidance of precipitating factors can lead to a better prognosis.