alpha-synuclein and Epilepsy

The search for noninvasive biomarkers of neuroinflammation and neurodegeneration has focused on various neurological disorders, including epilepsy. We sought to determine whether α-synuclein and cytokines are correlated with the degree of neuroinflammation and/or neurodegeneration in children with epilepsy and with acquired demyelinating disorders of the central nervous system (CNS), as a prototype of autoimmune neuroinflammatory disorders.. We analyzed serum and exosome levels of α-synuclein and serum proinflammatory and anti-inflammatory cytokines among 115 children with epilepsy and 10 acquired demyelinating disorders of the CNS and compared to 146 controls. Patients were enrolled prospectively and blood was obtained from patients within 48 h after acute afebrile seizure attacks or relapse of neurological symptoms. Acquired demyelinating disorders of the CNS include acute disseminated encephalomyelitis, multiple sclerosis, neuromyelitis optica spectrum disorders, and transverse myelitis. The controls were healthy age-matched children. The serum exosomes were extracted with ExoQuick exosome precipitation solution. Serum α-synuclein levels and serum levels of cytokines including IFN-β, IFN-γ, IL-1β, IL-6, IL-10 and TNF-α were measured using single and multiplex ELISA kits. Data were analyzed and compared with measures of disease severity, such as age at disease onset, duration of disease, and numbers of antiepileptic drug in use.. Serum α-synuclein levels were significantly increased in patients with epilepsy and acquired demyelinating disorders of the CNS compared to controls (both, p < 0.05) and showed correlation with measures of disease severity both in epilepsy (p < 0.05, r = 0.2132) and in acquired demyelinating disorders of the CNS (p < 0.05, r = 0.5892). Exosome α-synuclein showed a significant correlation with serum α-synuclein (p < 0.0001, r = 0.5915). Serum IL-1β levels were correlated only with the numbers of antiepileptic drug used in children with epilepsy (p < 0.001, r = 0.3428), suggesting drug resistant epilepsy.. This is the first study in children demonstrating that serum α-synuclein levels were significantly increased in children with epilepsy and with acquired demyelinating disorders of the CNS and correlated with measures of disease severity. Serum IL-1β levels showed significant correlation only with drug resistance in children with epilepsy. Thus, these data support that serum levels of α-synuclein and IL-1β are potential prognostic biomarkers for disease severity in children with epilepsy. CNS, central nervous system.

Topics: Adolescent; alpha-Synuclein; Biomarkers; Child; Cytokines; Encephalomyelitis, Acute Disseminated; Epilepsy; Female; Humans; Interleukin-10; Interleukin-1beta; Male; Multiple Sclerosis; Neuromyelitis Optica; Prognosis; Prospective Studies; Tumor Necrosis Factor-alpha

The present study was designed to examine the possible neuroprotective and antiepileptic effects of metformin (Metf) in a rat model of pentylenetetrazole (PTZ)-induced epilepsy and its possible underlying mechanisms. Forty male albino rats were assigned to 4 groups of equal size: (1) normal control (NC) group, (2) Metf group: daily treatment with Metf (200 mg/kg, i.p.) for 2 weeks, (3) PTZ group: treatment with PTZ (50 mg/kg, i.p.) every other day for 2 weeks, and (4) Metf + PTZ group: daily treatment with PTZ and metformin (200 mg/kg, i.p.) for 2 weeks. Administration of PTZ caused a significant increase in seizure score and duration, induced a state of oxidative stress (high malondialdehyde, low reduced glutathione and catalase activity), and led to the upregulation of β-catenin, caspase-3, and its cleavage products, Hsp70 and α-synuclein, in hippocampal regions as well as a significant reduction in seizure latency. While Metf treatment significantly ameliorated PTZ-induced seizures, attenuated oxidative stress, and upregulated α-synuclein and β-catenin expression, it also inhibited caspase-3 activation and the release of the cleavage product and caused more upregulation in Hsp70 expression in hippocampal regions (p < 0.05). In conclusion, the antiepileptic and neuroprotective effects of Metf in PTZ-induced epilepsy might be due to the inhibition of apoptosis, attenuation of oxidative stress and α-synuclein expression, and upregulation of Hsp70.

Topics: alpha-Synuclein; Animals; Apoptosis; Convulsants; Epilepsy; Male; Metformin; Pentylenetetrazole; Rats; Rats, Sprague-Dawley

Topics: alpha-Synuclein; Alzheimer Disease; Amyotrophic Lateral Sclerosis; Brain; C9orf72 Protein; Chronic Pain; Epilepsy; Genome-Wide Association Study; Humans; Mental Disorders; Neuralgia; Neurobiology; Neurodegenerative Diseases; Parkinson Disease; Proteins; tau Proteins; Tauopathies

Epilepsy is now recognized as the second most common neurological disease in China. To determine the genetic cause of epileptic encephalopathy, we performed a multiomics study using mouse models of controls, anticonvulsant mice treated with five drugs and epileptic mice. Based on genome-wide profiling analysis, we discovered four genes in the epileptic mouse group with differentially-expressed mRNA. After isobaric tags for relative and absolute quantification (iTRAQ) validation, only one gene, SNCA, remained, which was associated with apoptotic response of neuronal cells, and regulation of dopamine release and transport. We also identified three miRNAs targeting SNCA, out of which mmu-miR-21a-3p demonstrated a seven-fold change in expression between control and epileptic mice.

Topics: alpha-Synuclein; Animals; Epilepsy; Gene Expression Profiling; Male; Mice; MicroRNAs; Oligonucleotide Array Sequence Analysis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization