Antiepileptic drugs prevent changes in adenosine deamination during acute seizure episodes in adult zebrafish

Abstract

Adenosine is an endogenous modulator of brain functions, which presents anticonvulsant properties. In addition, its levels can be increased during neural injury. The modulation of extracellular adenosine levels by ectonucleotidase and adenosine deaminase (ADA) activities may represent a key mechanism in the control of epileptogenesis. In the present study, we investigated the effects of acute seizure episodes and antiepileptic drug (AED) treatments on ectonucleotidases and ADA activities in adult zebrafish brain. Our data have demonstrated that pentylenetetrazole (PTZ)-induced seizures did not alter ATP, ADP, and AMP hydrolysis in brain membrane fractions. However, there was a significant increase on ecto-ADA and soluble ADA activities in PTZ-treated animals immediately after a clonus-like convulsion and loss of posture, which are typical behavioral changes observed in Stage 3. Furthermore, our results have demonstrated that AED pretreatments prevented the stimulatory effect promoted by PTZ exposure on ADA activities. The PTZ and AED treatments did not promote alterations on ADA gene expression. Interestingly, when exposed to PTZ, animals pretreated with AEDs showed longer latency to reach the clonus-like seizure status, which is an effect that matches the suppression of the increase of ADA activity promoted by the AEDs. These data suggest that the adenosine deamination could be involved in the control of seizure development in zebrafish and may be modulated by AED treatments.

Role of Adenosine Signaling on Pentylenetetrazole-Induced Seizures in Zebrafish

“…37 However, one single seizure episode significantly increased ADA activity in the zebrafish brain, an effect that was suppressed by AED pretreatments. 38 AED pretreatments suppressed the increase in adenosine deamination, which coincides with a longer period to reach the tonic-clonic seizure status. 38 Therefore, ADA activity is modulated differently early after a single seizure or successive seizure episodes.…”

“…38 AED pretreatments suppressed the increase in adenosine deamination, which coincides with a longer period to reach the tonic-clonic seizure status. 38 Therefore, ADA activity is modulated differently early after a single seizure or successive seizure episodes. Evidence sustaining the approach of combating seizures by inhibiting ADA is limited.…”

“…35 Acute PTZ-induced seizures did not alter ectonucleotidase activities in zebrafish brain membranes. 37,38 Furthermore, there were no differences on ectonucleotidase activities after a single PTZ exposure in rats. However, increased ATP hydrolysis was evident in rats that were more resistant to seizures after the PTZ-kindling treatment.…”

Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish

“…PTZinduced seizures both in larval and adult zebrafish caused behavioral, molecular, and electrographic alterations that would be expected from a seizure episode (Baraban et al, 2005;Pineda et al, 2011). In addition, both larval and adult zebrafish show response to classic antiepileptic drugs (AEDs), such as valproate (VPA), carbamazepine, and phenytoin (Berghmans et al, 2007;Lee et al, 2010;Siebel et al, 2013).…”

Zebrafish as a Model to Study Autism Spectrum Disorder Caused by Environmental Chemicals Exposure

“…This model is widely considered to offer numerous logistical and economic advantages over mammalian models as zebrafish spawn overnight, hatch in 2-3 days post fertilization, develop complex behavior within the first week of life, and reach sexual maturity in 2-3 months [19]. Zebrafish have been proposed as a model of Alzheimer´s disease [20,21], schizophrenia [22], drug abuse [23], and other brain disorders [24,25]. The utility of both adult and larval zebrafish in neuroscience has grown markedly in the past decades because it is a vertebrate species with high physiological and genetic homology to humans (69% of zebrafish genes have human orthologs meaning that it is frequently possible to study human disease-related genes in fish), and also because of the ease of genetic manipulation, fully characterized genome [24,[26][27][28][29][30][31].…”