scholarly journals Altered Protein Profiles During Epileptogenesis in the Pilocarpine Mouse Model of Temporal Lobe Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Md. Mahiuddin Ahmed ◽  
Andrew J. Carrel ◽  
Yasmin Cruz Del Angel ◽  
Jessica Carlsen ◽  
Ajay X. Thomas ◽  
...  
Keyword(s):  
Mouse Model ◽  
Significant Proportion ◽  
Molecular Alterations ◽  
Multiple Components ◽  
Spontaneous Seizures ◽  
Apoptosis Pathways ◽  
Profile Changes ◽  
Acquired Epilepsy ◽  
Brain Insults ◽  
Related Proteins

Epilepsy is characterized by recurrent, spontaneous seizures and is a major contributor to the global burden of neurological disease. Although epilepsy can result from a variety of brain insults, in many cases the cause is unknown and, in a significant proportion of cases, seizures cannot be controlled by available treatments. Understanding the molecular alterations that underlie or are triggered by epileptogenesis would help to identify therapeutics to prevent or control progression to epilepsy. To this end, the moderate throughput technique of Reverse Phase Protein Arrays (RPPA) was used to profile changes in protein expression in a pilocarpine mouse model of acquired epilepsy. Levels of 54 proteins, comprising phosphorylation-dependent and phosphorylation-independent components of major signaling pathways and cellular complexes, were measured in hippocampus, cortex and cerebellum of mice at six time points, spanning 15 min to 2 weeks after induction of status epilepticus. Results illustrate the time dependence of levels of the commonly studied MTOR pathway component, pS6, and show, for the first time, detailed responses during epileptogenesis of multiple components of the MTOR, MAPK, JAK/STAT and apoptosis pathways, NMDA receptors, and additional cellular complexes. Also noted are time- and brain region- specific changes in correlations among levels of functionally related proteins affecting both neurons and glia. While hippocampus and cortex are primary areas studied in pilocarpine-induced epilepsy, cerebellum also shows significant time-dependent molecular responses.

scholarly journals Anti-Epileptogenic Effects of Antiepileptic Drugs

2020 ◽  
Vol 21 (7) ◽  
pp. 2340
Author(s):  
Barbara Miziak ◽  
Agnieszka Konarzewska ◽  
Marzena Ułamek-Kozioł ◽  
Monika Dudra-Jastrzębska ◽  
Ryszard Pluta ◽  
...  
Keyword(s):  
Experimental Data ◽  
Antiepileptic Drugs ◽  
Affirmative Answer ◽  
Protective Activity ◽  
Neuroprotective Effects ◽  
Spontaneous Seizures ◽  
High Doses ◽  
Acquired Epilepsy ◽  
Brain Insults ◽  
The Brain

Generally, the prevalence of epilepsy does not exceed 0.9% of the population and approximately 70% of epilepsy patients may be adequately controlled with antiepileptic drugs (AEDs). Moreover, status epilepticus (SE) or even a single seizure may produce neurodegeneration within the brain and SE has been recognized as one of acute brain insults leading to acquired epilepsy via the process of epileptogenesis. Two questions thus arise: (1) Are AEDs able to inhibit SE-induced neurodegeneration? and (2) if so, can a probable neuroprotective potential of particular AEDs stop epileptogenesis? An affirmative answer to the second question would practically point to the preventive potential of a given neuroprotective AED following acute brain insults. The available experimental data indicate that diazepam (at low and high doses), gabapentin, pregabalin, topiramate and valproate exhibited potent or moderate neuroprotective effects in diverse models of SE in rats. However, only diazepam (at high doses), gabapentin and pregabalin exerted some protective activity against acquired epilepsy (spontaneous seizures). As regards valproate, its effects on spontaneous seizures were equivocal. With isobolography, some supra-additive combinations of AEDs have been delineated against experimental seizures. One of such combinations, levetiracetam + topiramate proved highly synergistic in two models of seizures and this particular combination significantly inhibited epileptogenesis in rats following status SE. Importantly, no neuroprotection was evident. It may be strikingly concluded that there is no correlation between neuroprotection and antiepileptogenesis. Probably, preclinically verified combinations of AEDs may be considered for an anti-epileptogenic therapy.

scholarly journals The Heat Sensing Trpv1 Receptor Is Not a Viable Anticonvulsant Drug Target in the Scn1a+/− Mouse Model of Dravet Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Vaishali Satpute Janve ◽  
Lyndsey L. Anderson ◽  
Dilara Bahceci ◽  
Nicole A. Hawkins ◽  
Jennifer A. Kearney ◽  
...  
Keyword(s):  
Mouse Model ◽  
Drug Target ◽  
Genetic Modifier ◽  
Anticonvulsant Drug ◽  
Dravet Syndrome ◽  
Seizure Threshold ◽  
Drug Resistant ◽  
Spontaneous Seizures ◽  
Temperature Thresholds ◽  
Seizure Models

Cannabidiol has been approved for the treatment of drug-resistant childhood epilepsies including Dravet syndrome (DS). Although the mechanism of anticonvulsant action of cannabidiol is unknown, emerging data suggests involvement of the transient receptor potential cation channel subfamily V member 1 (Trpv1). Pharmacological and genetic studies in conventional seizure models suggest Trpv1 is a novel anticonvulsant target. However, whether targeting Trpv1 is anticonvulsant in animal models of drug-resistant epilepsies is not known. Thus, we examined whether Trpv1 affects the epilepsy phenotype of the F1.Scn1a+/− mouse model of DS. We found that cortical Trpv1 mRNA expression was increased in seizure susceptible F1.Scn1a+/− mice with a hybrid genetic background compared to seizure resistant 129.Scn1a+/− mice isogenic on 129S6/SvEvTac background, suggesting Trpv1 could be a genetic modifier. Previous studies show functional loss of Trpv1 is anticonvulsant. However, Trpv1 selective antagonist SB-705498 did not affect hyperthermia-induced seizure threshold, frequency of spontaneous seizures or survival of F1.Scn1a+/− mice. Surprisingly, Trpv1 deletion had both pro- and anti-seizure effects. Trpv1 deletion did not affect hyperthermia-induced seizure temperature thresholds of F1.Scn1a+/−; Trpv1+/− at P14-16 but was proconvulsant at P18 as it reduced seizure temperature thresholds. Conversely, Trpv1 deletion did not alter the frequency of spontaneous seizures but reduced their severity. These results suggest that Trpv1 is a modest genetic modifier of spontaneous seizure severity in the F1.Scn1a+/− model of DS. However, the opposing pro- and anti-seizure effects of Trpv1 deletion and the lack of effects of Trpv1 inhibition suggest that Trpv1 is unlikely a viable anticonvulsant drug target in DS.

scholarly journals Reductions in Hydrogen Sulfide Precede Onset of Mitochondrial Quality Control in the Corneal Kindled Mouse Model of Epilepsy

2021 ◽  
Author(s):  
Christi Cho ◽  
Maxwell Zeigler ◽  
Stephanie Mizuno ◽  
Richard S. Morrison ◽  
Rheem Totah ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Mouse Model ◽  
Membrane Integrity ◽  
Brain Homogenate ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Mitochondrial Stress ◽  
Acute Seizures ◽  
Related Proteins

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

scholarly journals A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer

Oncogene ◽  
2018 ◽  
Vol 37 (14) ◽  
pp. 1911-1925 ◽  
Author(s):  
Damiano Fantini ◽  
Alexander P. Glaser ◽  
Kalen J. Rimar ◽  
Yiduo Wang ◽  
Matthew Schipma ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mouse Model ◽  
Human Muscle ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Molecular Alterations ◽  
Muscle Invasive

scholarly journals The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1353
Author(s):  
Ji Hyun Kim ◽  
Sanghyun Lee ◽  
Eun Ju Cho
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
High Fat Diet ◽  
Ethyl Acetate Fraction ◽  
Control Group ◽  
Protective Effects ◽  
High Fat ◽  
Acer Okamotoanum ◽  
Related Proteins ◽  
The Brain

Obesity increases risk of Alzheimer’s Disease (AD). A high fat diet (HFD) can lead to amyloidosis and amyloid beta (Aβ) accumulation, which are hallmarks of AD. In this study, protective effects of the ethyl acetate fraction of Acer okamotoanum (EAO) and isoquercitrin were evaluated on obesity and amyloidosis in the HFD- and Aβ-induced mouse model. To induce obesity and AD by HFD and Aβ, mice were provided with HFD for 10 weeks and were intracerebroventricularly injected with Aβ25–35. For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally. Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice. Additionally, EAO- and isoquercitrin-administered groups attenuated abnormal adipokines release via a decrease in leptin and an increase in adiponectin levels compared with the control group. Furthermore, HFD and Aβ-injected mice had damaged liver tissues, but EAO- and isoquercitrin-administered groups attenuated liver damage. Moreover, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice. This study indicated that EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

scholarly journals Amazon rainforest rodents (Proechimys) are resistant to post-stroke epilepsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nancy N. Ortiz-Villatoro ◽  
Selvin Z. Reyes-Garcia ◽  
Leandro Freitas ◽  
Laís D. Rodrigues ◽  
Luiz E. C. Santos ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Laboratory Research ◽  
Post Injury ◽  
Post Stroke ◽  
Brain Responses ◽  
Conventional Animal ◽  
Acquired Epilepsy ◽  
Brain Insults

AbstractThere are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar’s brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

Sign in / Sign up

Export Citation Format

Share Document