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Experimental Animals Nov 2023Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications...
Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications (PTMs) are important protein functional regulators that regulate various physiological and pathological processes. It is significant for cell activity, stability, protein folding, and localization. Phosphoglycerate kinase (PGK) 1 has traditionally been studied as an important adenosine triphosphate (ATP)-generating enzyme of the glycolytic pathway. PGK1 catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. In addition to cell metabolism regulation, PGK1 is involved in multiple biological activities, including angiogenesis, autophagy, and DNA repair. However, the exact role of PGK1 succinylation in epilepsy has not been thoroughly investigated. The expression of PGK1 succinylation was analyzed by Immunoprecipitation. Western blots were used to assess the expression of PGK1, angiostatin, and vascular endothelial growth factor (VEGF) in a rat model of lithium-pilocarpine-induced acute epilepsy. Behavioral experiments were performed in a rat model of lithium-pilocarpine-induced acute epilepsy. ELISA method was used to measure the level of S100β in serum brain biomarkers' integrity of the blood-brain barrier. The expression of the succinylation of PGK1 was decreased in a rat model of lithium-pilocarpine-induced acute epilepsy compared with the normal rats in the hippocampus. Interestingly, the lysine 15 (K15), and the arginine (R) variants of lentivirus increased the susceptibility in a rat model of lithium-pilocarpine-induced acute epilepsy, and the K15 the glutamate (E) variants, had the opposite effect. In addition, the succinylation of PGK1 at K15 affected the expression of PGK1 succinylation but not the expression of PGK1total protein. Furthermore, the study found that the succinylation of PGK1 at K15 may affect the level of angiostatin and VEGF in the hippocampus, which also affects the level of S100β in serum. In conclusion, the mutation of the K15 site of PGK1 may alter the expression of the succinylation of PGK1 and then affect the integrity of the blood-brain barrier through the angiostatin / VEGF pathway altering the activity of epilepsy, which may be one of the new mechanisms of treatment strategies.
Topics: Rats; Animals; Phosphoglycerate Kinase; Vascular Endothelial Growth Factor A; Blood-Brain Barrier; Lithium; Pilocarpine; Angiostatins; Seizures; Epilepsy; Adenosine Triphosphate
PubMed: 37258131
DOI: 10.1538/expanim.23-0019 -
Archivos de La Sociedad Espanola de... Jul 2021The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since...
The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID 19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.
Topics: Adult; COVID-19; Female; Humans; Tonic Pupil
PubMed: 34217472
DOI: 10.1016/j.oftale.2021.01.001 -
Molecules (Basel, Switzerland) Jun 2021Furan-2-carboxylic acid was used as a starting material for the synthesis of dehydro-homopilopic acid. Esterification, hydrogenation and enzymatic hydrolysis followed by...
Furan-2-carboxylic acid was used as a starting material for the synthesis of dehydro-homopilopic acid. Esterification, hydrogenation and enzymatic hydrolysis followed by the reduction of Weinreb amides and a single-step attachment of a 1-methyl-imidazole residue allowed for the concise synthesis of both enantiomers of pilocarpine.
Topics: 4-Butyrolactone; Amides; Carboxylic Acids; Esterification; Furans; Hydrogenation; Hydrolysis; Pilocarpine; Stereoisomerism
PubMed: 34208623
DOI: 10.3390/molecules26123676 -
Epilepsia Dec 2022Individuals use the observation of a conspecific to learn new behaviors and skills in many species. Whether observational learning is affected in epilepsy is not known....
Individuals use the observation of a conspecific to learn new behaviors and skills in many species. Whether observational learning is affected in epilepsy is not known. Using the pilocarpine rat model of epilepsy, we assessed learning by observation in a spatial task. The task involves a naive animal observing a demonstrator animal seeking a reward at a specific spatial location. After five observational sessions, the observer is allowed to explore the rewarded space and look for the reward. Although control observer rats succeed in finding the reward when allowed to explore the rewarded space, epileptic animals fail. However, epileptic animals are able to successfully learn the location of the reward through their own experience after several trial sessions. Thus, epileptic animals show a clear deficit in learning by observation. This result may be clinically relevant, in particular in children who strongly rely on observational learning.
Topics: Rats; Animals; Epilepsy
PubMed: 36197904
DOI: 10.1111/epi.17421 -
Journal of Neuro-ophthalmology : the... Dec 2021A 37-year-old patient presented to our emergency department with sudden onset decreased vision with a history of being treated for COVID 19 3 weeks earlier. On...
A 37-year-old patient presented to our emergency department with sudden onset decreased vision with a history of being treated for COVID 19 3 weeks earlier. On examination, she was found to have a tonic right pupil, which was confirmed with a dilute pilocarpine test. As tonic pupils are known to be caused by neurotropic viruses and our current understanding of the SARS-CoV-2 is that it does affect the nervous system, we feel that the tonic pupil in our patient may be secondary to COVID 19.
Topics: Adult; COVID-19; Female; Humans; Tonic Pupil
PubMed: 33492032
DOI: 10.1097/WNO.0000000000001221 -
Brazilian Journal of Biology = Revista... 2022The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure...
The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability period. In the present work, we describe the effects of dopamine depletion after the administration of 6-hidroxidopamine (6-OHDA) into the substantia nigra pars compacta of male rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus (SE), as well as spontaneous and recurrent seizures (SRSs) frequency during the chronic period of the model were determined. Since the hippocampus is one of main structures in the development of this experimental model of epilepsy, the dopamine levels in this region were also determined after drug administration. In the first experiment, 62% (15/24) of 6-OHDA pre-treated rats and 45% (11/24) of those receiving ascorbic acid as control solution progressed to motor limbic seizures evolving to SE, after the administration of pilocarpine. Severeness of seizures during the model´s the acute period, was significantly higher in epileptic experimental rats (56.52%), than in controls (4.16%). In the second experiment, the frequency of seizures in the model's chronic phase did not significantly change between groups. Our data show that dopamine may play an important role on seizure severity in the pilo's model acute period, which seems to be due to dopamine inhibitory action on motor expression of seizure.
Topics: Animals; Dopamine; Epilepsy; Male; Muscarinic Agonists; Oxidopamine; Pilocarpine; Rats; Rats, Wistar; Seizures; Status Epilepticus
PubMed: 35544785
DOI: 10.1590/1519-6984.248411 -
Brain Sciences Feb 2023Epilepsy is a neurological disease and approximately 30% of patients have failed to respond to current anti-epilepsy drugs. The neuroinflammation mechanism has raised...
Epilepsy is a neurological disease and approximately 30% of patients have failed to respond to current anti-epilepsy drugs. The neuroinflammation mechanism has raised increasing concerns and been regarded as the novel treatment strategy in epilepsy, but the target molecules require further research. Pyruvate kinase isoform 2 (PKM2) is well studied in peripheral inflammation, but its role in epilepsy neuroinflammation remains unclear. We knocked down microglia PKM2 in the hippocampus using a stereotaxic adeno-associated virus (AAV) microinjection and established a pilocarpine-induced status epilepticus (PISE) model. Racine score was used to evaluate the seizure grade. Next, we used WB, Multiplex tyramide signal amplification (TSA) staining and other methods to determine neuroinflammation and the complement component 3 (C3)-C3aR interaction in primary microglia. Results showed that microglia PKM2 knockdown reduced epilepsy grade and rescued neuron loss. Mechanistically, PKM2 knockdown inhibited microglia activation and inflammation factor secretion through suppressing p65 expression and phosphorylation. The reduced microglia C1q, TNF-α, and IL-1α were responsible for the decreased astrocyte C3 expression and the following neuron damage caused by the C3-C3aR interaction. Our data suggest that microglia PKM2 inhibition ameliorates neuroinflammation and neuron loss through C3-C3aR interaction in epilepsy, which provides an attractive target for the intervention of damaged neuron-glia crosstalk in epilepsy.
PubMed: 36831807
DOI: 10.3390/brainsci13020262 -
International Journal of Molecular... Apr 2023This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and... (Review)
Review
This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and adults, and many aspects of this disease are still poorly understood. In vivo and in vitro models derived from rodents are the most widely used for studying both epilepsy pathophysiology and novel drug treatments. However, researchers have recently obtained several valuable insights into these two fields of investigation by studying ZF. Despite the relatively simple brain structure of these animals, researchers can collect large amounts of data in a much shorter period and at lower costs compared to classical rodent models. This is particularly useful when a large number of candidate antiseizure drugs need to be screened, and ethical issues are minimized. In ZF, seizures have been induced through a variety of chemoconvulsants, primarily pentylenetetrazol (PTZ), kainic acid (KA), and pilocarpine. Furthermore, ZF can be easily genetically modified to test specific aspects of monogenic forms of human epilepsy, as well as to discover potential convulsive phenotypes in monogenic mutants. The article reports on the state-of-the-art and potential new fields of application of ZF research, including its potential role in revealing epileptogenic mechanisms, rather than merely assessing iatrogenic acute seizure modulation.
Topics: Animals; Child; Humans; Zebrafish; Anticonvulsants; Epilepsy; Seizures; Pentylenetetrazole; Disease Models, Animal
PubMed: 37175408
DOI: 10.3390/ijms24097702 -
Archivos de La Sociedad Espanola de... Jul 2021The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since...
The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID-19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.
PubMed: 34629696
DOI: 10.1016/j.oftal.2021.01.003