AUTHOR=Taha Ameer Y. , Trepanier Marc-Olivier , Coibanu Flaviu A. , Saxena Anjali , Jeffrey Melanie A. , Taha Nadeen M. Y. , Burnham W. McIntyre , Bazinet Richard P. 

TITLE=Dietary Omega-3 Polyunsaturated Fatty Acid Deprivation Does Not Alter Seizure Thresholds but May Prevent the Anti-seizure Effects of Injected Docosahexaenoic Acid in Rats

JOURNAL=Frontiers in Neurology

VOLUME=Volume 9 - 2018

YEAR=2019

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.01188

DOI=10.3389/fneur.2018.01188

ISSN=1664-2295

ABSTRACT=Background: Brain concentrations of omega-3 docosahexaenoic acid (DHA, 22:6n-3) have been reported to positively correlate with seizure thresholds in rodent seizure models. It is not known whether brain DHA depletion, achieved by chronic dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency, lowers seizure thresholds in rats.
Objective: The present study tested the hypothesis that lowering brain DHA concentration with chronic dietary n-3 PUFA deprivation in rats will reduce seizure thresholds, and that compared to injected oleic acid (OA), injected  DHA will raise seizure thresholds in rats maintained on n-3 PUFA adequate and deficient diets.
Methods: Rats (60 days old) were surgically implanted with electrodes in the amygdala, and subsequently randomized to the AIN-93G diet containing adequate levels of n-3 PUFA derived from soybean oil or an n-3 PUFA-deficient diet derived from coconut and safflower oil. The rats were maintained on the diets for 37 weeks. Afterdischarge seizure thresholds (ADTs) were measured every 4 to 6 weeks by electrically stimulating the amygdala. Between weeks 35 to 37, ADTs were assessed within one hour of subcutaneous OA or DHA injection (600 mg/kg). Seizure thresholds were also measured in a parallel group of non-implanted rats subjected to the maximal pentylenetetrazol (PTZ, 110 mg/kg) seizure test. PUFA composition was measured in the pyriform-amygdala complex of another group of non-implanted rats sacrificed at 16 and 32 weeks.  
Results: Dietary n-3 PUFA deprivation did not significantly alter amygdaloid seizure thresholds or latency to PTZ-induced seizures. Acute injection of OA did not alter amygdaloid ADT, whereas acute DHA raised amygdaloid ADT in rats on the n-3 PUFA adequate control diet as compared to rats on the  n-3 PUFA deficient diet (P<0.05). Pyriform-amygdala DHA percent composition did not significantly differ between the groups, while n-6 docosapentaenoic acid, a marker of n-3 PUFA deficiency, was significantly increased by 2.9 fold at 32 weeks.
Conclusion: Chronic dietary n-3 PUFA deficiency does not alter seizure thresholds in rats, but may prevent the anti-seizure effects of DHA.