Check this out before we begin!
Big shot out to Professor MJG for telling me that Epilepsy and Depression is an interesting subject!!
So, the general idea behind the relationship between these two disorders is quite cool. Interlukin-1β (IL-1β) is another one of those cytokines that modulate immune response to foreign organisms. Clinical and experimental studies have found that Temporal Lobe Epilepsy (TLE) causes hippocampal inflammation and enhanced binding of IL-β to IL-β receptors. Furthermore, experiments have shown that higher levels of IL-1β may contribute to the etiology of depression by disrupting the HPA axis. This particular paper aims to put one- and-one together. Specifically, the researchers hypothesize that the blockade of hippocampal IL-1β receptor binding by an IL-β receptor antagonist will have an antidepressant effect immediately following pilocarpin status epilepticus (SE).
Allow me to break it down. First, male wistar rats are subjected to a force swim test and saccharin preference test. Immediately following the behavioral test, one group was given lithium chloride (LiCl) and pilocarpine to induce epilepsy while another group served as a control. For the next 10 weeks, the IL-1ra was administered to a sub- group in the epileptic group and the naïve group. A forced swim and saccharin test preference test were conducted in the final 2 weeks of the experiment. Additionally, the rats were given a fast cyclic voltammetry (FAV) test, which monitors the raphe-hippocampal serotonergic transmission. I know you’re asking where this little small procedure fits in the puzzle? As you know, altered 5-HT secretion is a classic symptom of depression. FYI: the rats never survive the FAV test.
The results were interesting. Post SE rats treated with IL-1ra had a higher immobility time in the forced swim test compared to themselves pre SE and post SE controls. However, treatment with IL-1ra attenuated the effects of SE because they spent less time immobile. Additionally, in comparison with the untreated and saline rats, treatment with IL-1ra restored saccharine preference, lowered basal corticosterone (CORT) levels, mitigated the extreme reaction to dexamethasone (DEX) after CRH stimulation, limited the exposure to high concentrations of CORT and restored changes in 5-HT secretion from the hippocampus.
What is the moral of the story? The authors argue that IL-1ra did attenuate (to a degree) the symptoms of depression caused by epilepsy, but the true problem may lie downstream. Can anyone ever find one particular place “downstream?” This is what intrigues and frustrates me about biology research (I get even frustrated at myself because I have used this same sentence in a presentation). Epilepsy and depression probably influences all systems in the body!!! Why do we need to point out one huge disruption and run with it? Even when we try to represent different aspects of a mental disorder or a biological disorder in rat models, we start to ignore the problems that can arise in other parts of the CNS/PNS. I suppose we have must isolate two or three aspects of the disorder for the sake of lab research. Oh well. Thank goodness for the hierarchy of clinical trials because people would be screwed if they had to rely solely on biology research.
Back on topic! It sounds like IL-1ra’s can be included in the cocktail I talked about in my last post. This article definitely sounds like another one of those situations where everything is reduced to biology (e.g. neuroimmunology). At least they had behavioral measurements! Perhaps they deserve a handclap?
Just in case you are dying to learn more:
Mazarati, A.M., Pineda, E., Shin, D., Tio, D., Taylor, A.N., & Sankar, R. (2010). Comobidity between epilepsy and depression: Role of hippocampal interleukin-1β. Neurobiology of Disease, 37, 461-467.
3 thoughts on “Dude…The Epilepsy and Depression Concert is Downstream.”
I’ll give them a handclap! And I didn’t yet look at the paper but it sounds like it was decently executed as well. Two handclaps! I really think the link between depression and epilepsy is a great illustration of what we are discussing.
I love your enthusiasm for this topic, Sharonda! Also, excellent job at elucidating the findings in such a way that it’s really easy to understand. I think it is fascinating how many pathologies have a hand in the depression pot. Very interesting.
This seems especially relevant because of the article we read for tomorrow’s class about how depression may be linked to a lack of regeneration in the brain. This is directly related to epilepsy and discovering new and improved ways to treat depression! I know neuronal regeneration is a fairly new topic in the field but this is great research in depression. It’s encouraging to know there is still so much we are learning about the human brain as well as behavior.