Does Consumption of a Western Diet During Early Development Exacerbate Hippocampal Microgliosis After Pilocarpine-Induced Status Epilepticus?

Cynthia D Alvarado, Purdue University

Abstract

Rationale:Western diet (WD) consumption has been identified as a contributing source of proinflammatory responses in the brain, as demonstrated by elevated cytokines and microgliosis. Evidence from rodent studies suggests that these proinflammatory effects are seen globally in the brain, including in the hippocampus, suggesting a role for WD contributing to pathophysiological disruptions to brain function. Moreover, hippocampal microgliosis is a hallmark not only in experimental models of seizure disorders but also in acquired epilepsy in humans. Inflammatory responses of the brain to insults, as in the case of epilepsy, are modulated by microglia—the resident immune cells of the brain. Activation and proliferation of microglia contributes to the development and progression of spontaneous recurring seizures, and ultimately epilepsy. Because WD consumption also engages microglia in inflammatory responses in rodent models, WD consumption that occurs prior to a seizure-related insult might potentially prime the hippocampus for exacerbated responses. The potential interaction between WD consumption, epilepsy and hippocampal pathology has been relatively unexplored. Furthermore, the effects of early developmental exposure to WD on seizures or acquired epilepsies have not been studied. These interactions are important to examine in light of increasing rates of WD consumption in the U.S. According to the latest USDA data, 70% of the population exceed the recommended dietary intake of added sugars and saturated fats (Flegal et al., 2016). Along with rising rates of WD consumption, rates of epilepsy in children in the U.S. have increased by 5% in the past decade, and there are currently close to 500,000 cases (Zack & Kobau, 2015). The goal of the present experiments is to use a rat model of acquired temporal lobe epilepsy—pilocarpine-induced SE—to test the hypothesis that WD exacerbates the inflammatory changes following SE neuronal injury in hippocampus of rats. Our central hypothesisis that consumption of WD during early development will produce an inflammatory state which will prime the hippocampus for greater neuroinflammation following SE. Methods:The goal of this study is to use a rat model of acquired temporal lobe epilepsy, pilocarpine-induced status epilepticus (SE), to test the hypothesis that WD exacerbates the inflammatory consequences of SE in hippocampus of male rats. Testing this hypothesis in animals consuming WD from early in life may provide insight into how a modifiable environmental factor could influence the development of seizure disorders. Results:We found no significant differences in body weight at induction, or latency to SE after pilocarpine injection in animals on a WD compared to a standard control diet. There were no differences in time to sedation after diazepam injection or in time to recovery from diazepam in animals that reached SE across the diets. Analysis of Iba1+ cells number revealed no differences in microgliosis between diet or seizure groups or across hippocampal regions of interest. Morphological assessment per hippocampal area did not show significant differences between diet or seizure groups across hippocampal areas. Thus, under the current conditions, microgliosis was not produced by consumption of a WD during early development; it was not observed 4 hours after seizure induction in animals consuming a control diet; and there was no evidence that WD exacerbated any effects of pilocarpine. We found no significant differences in body weight at induction, or latency to SE after pilocarpine injection in animals on a WD compared to a standard control diet. There were no differences in time to sedation after diazepam injection or in time to recovery from diazepam in animals that reached SE across the diets. Analysis of Iba1+ cells number revealed no differences in microgliosis between diet or seizure groups or across hippocampal regions of interest. Morphological assessment per hippocampal area did not show significant differences between diet or seizure groups across hippocampal areas. Thus, under the current conditions, microgliosis was not produced by consumption of a WD during early development; it was not observed 4 hours after seizure induction in animals consuming a control diet; and there was no evidence that WD exacerbated any effects of pilocarpine.

Degree

M.Sc.

Advisors

Swithers, Purdue University.

Subject Area

Pathology|Morphology|Behavioral Sciences|Cognitive psychology|Immunology|Neurosciences|Physiology|Psychology|Public health

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