Your Brain: Mossy Cells and the Fight Against Epilepsy - Prof. Helen Scharfman, NYU Langone Medical Center & NKI for Psychiatric Research, USA
Helen Scharfman, a professor and research scientist, discusses her extensive research on the epilepsies, particularly focusing on mossy cells in the temporal lobe! She explains the significance of these cells in understanding seizures and anxiety, and the potential for future treatments/preventions! Helen emphasises the importance of patient involvement in research and the international, collaborative nature of scientific discovery! Transcription and links to Helen are below! 👇🏻
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
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00:00 Helen Scharfman
“We're very excited not only about trying to reduce seizures, but also reduce the comorbidities!”
00:10 Torie Robinson
The most common type of epilepsy - in the world - is temporal lobe epilepsy. Our temporal lobes - or at least parts of it - appear to be very sensitive - making them vulnerable to epileptogenesis - or epilepsy onset! Well, today, top neuroscientist professor Helen Scharfman talks about how understanding mossy cells (a type of neuron that hangs out in the temporal lobe) could help form a solution to preventing seizures - and their best mates; anxiety, and depression!
If you haven’t done so already, please do like and comment on this episode, and subscribe to our channel, so as to get way more people around the world learning about the epilepsies!
00:50 Helen Scharfman
First of all thank you so much for having me and I am a professor at NYU in the Medical Center in Child and Adolescent Psychiatry, Neuroscience, and Physiology, and Psychiatry and I'm a research scientist at the Nathan Kline Institute for Psychiatric Research in Orangeburg, New York; where I have my laboratory, and I have been studying (for several decades now) the mechanisms of excitability and plasticity in the normal brain and trying to use what we've learned to understand complex diseases like epilepsy.
01:37 Torie Robinson
And why focus on the epilepsies though? Because there's so many interesting activities of an unhealthy brain. Why the epilepsies?
01:44 Helen Scharfman
Initially, in college, I started getting exposed to epilepsy - I didn't know anyone, but I started to read about it, learn about it, and I just thought it was a devastating disorder. And, I was both fascinated by how one could have seizures - such a catastrophic event, but I was also… felt so terrible for the individuals who have that in their families!
20:14 Torie Robinson
Mm-hmm.
02:14 Helen Scharfman
And the more I learned, the more I became interested and sort of devoted to trying to actually develop better treatments for this terrible disease, maybe prevent it entirely.
02:31 Torie Robinson
And also, what I think kind of drew us together beforehand, also, was that I know that you see beyond the seizures and actually in the…
02:39 Helen Scharfman
Mmm.
02:39 Torie Robinson
…sort of, interictal periods of a person's life; which brings us onto your research really into mossy cells! So tell us what even are these things? Because they're not like the moss you find on a wall or something!
02:52 Helen Scharfman
The mossy cells are a small population of neurons in everybody's brain and they look structurally like they're mossy!
03:04 Torie Robinson
Ahh!
03:04 Helen Scharfman
Which is why they got their name! And I got interested in them as a postdoctoral fellow because they were implicated in diseases like epilepsy but people really didn't know much about them functionally! And so I was training to understand how to study neurons physiologically and started to study them for that reason and try to understand more about them.
03:31 Torie Robinson
And whereabouts do they hang out in one's brain?
03:34 Helen Scharfman
So, they hang out exclusively in the temporal lobe in an area of the hippocampus called the dentate gyrus…
03:42 Torie Robinson
Mm-hmm.
03:42 Helen Scharfman
..which we've come to understand is very, very important in epilepsy - but also in normal function! There are many roles the dentate gyrus plays in memory, normally, but also in regulating mood and anxiety. So, it's really a fascinating area.
04:02 Torie Robinson
I guess… has studying these mossy cells been something that's given you greater insight into the impacts of the epilepsies - beyond seizures?
04:11 Helen Scharfman
Broadly, the international community, over the last decades have developed very advanced molecular techniques to selectively activate and suppress different types of neurons in the brain and we've been able to apply those to the mossy cells - as have many other laboratories. And together, it's become fairly clear that these really are very important cells that regulate not only memory and anxiety but also epilepsy. And that's using rodent models of disease. So, and of course we'd like to do much more with humans, that's, nobody's offering us their mossy cells right now.
04:59 Torie Robinson
Although, do you not sometimes get access to mossy cells through surgeries? So people have had a lobectomy for instance, do you get hold of them that way?
05:06 Helen Scharfman
In humans, it is true that we can get tissue, and it's been fantastic that surgeons have made some of that tissue available. And what we've come to understand is that both something fascinating but a problem for research: the fascinating part is that mossy cells are quite vulnerable in this disease, so many of them are lost! But, what's fascinating is why are they so vulnerable? And moreover if we can protect them can we possibly prevent, delay or ameliorate the disease?!
05:45 Torie Robinson
So, you're saying that these mossy cells are very vulnerable, like, delicate, they can be easily destroyed by abnormal activity such as seizures, but also, potentially; if you protect these cells you can potentially use them to minimise seizure risk or seizure onset.
06:03 Helen Scharfman
Well, that is our hope. I think there are a lot of things there that we don't know and we've wanted to know for really many, many years. So now we're trying to establish cause and effect in the rodent models. So, the human tissue has been vital to our hypotheses, but now we're trying to get more evidence for our hypotheses using the rodent model.
06:29 Torie Robinson
So, doing all this research, right…. so research takes so much longer than anybody realises if they're not in the sphere. What do you see, what are your discoveries, to date, and what do you foresee the next 5, 10, 15 years bringing?
06:44 Helen Scharfman
Right now we're working on a hypothesis that mossy cells play a very important and regulatory role in the initial part of the development of epilepsy or epileptogenesis. And they have a very different but also important potential role after epilepsy's been established! So first of all, that's a sort of a novel hypothesis; how can there be different roles? But it's also a very exciting hypothesis because if we're right, we might, knowing what we know, we might be able to treat the initial stage to help prevent or ameliorate epilepsy! And also, knowing what we know, we might use a different approach but we might be able to protect people from seizures once epilepsy is established.
07:41 Torie Robinson
Say that you could do what you've proposed, would that just be of benefit to the people experiencing the seizures? Or would it be of benefit to helping control mood abnormalities, for instance?
07:54 Helen Scharfman
The way the mossy cells in the normal brain are certainly important in regulating memory, and mood, and anxiety, so you would expect that they would have roles in epilepsy as well, perhaps even more of a role! So we're very excited; not only about trying to reduce seizures, but also reduce the comorbidities.
08:54 Torie Robinson
Which would, as a whole (fingers crossed!)...the way things look, is to improve the overall quality of life of the people affected.
08:32 Helen Scharfman
Right, and there are some people who have found that even when they don't protect against seizures, they really can improve the comorbidities that they see. And so we're very excited because we hope to control both. But even if we get one - hahaha…
08:55 Torie Robinson
Yeah!! Hahaha!
08:56 Helen Scharfman
..we'll be feeling very good!
08:59 Torie Robinson
Thank you, and you know what, you saying that that shows a real understanding for what life can be like for people with an epilepsy - ‘cause sometimes we'll say “Mate, if you could just sort one of the symptoms out, mate, that would be fabulous, thank you!”.
09:12
09:11 Helen Scharfman
Well, I want to applaud you for all that you're doing to bring this topic to the fore and also for all the efforts to make it clear what the patients need. So, you know, a lot of us really are listening and welcome the opportunity to speak to wonderful people like you.
09:35 Torie Robinson
Well, thank you. I mean, I guess you've kind-of summarised it in a lovely way that, you know, PPI or public patient involvement can be really valuable, I think, to studies. I know not everyone around the globe does it, but working in that role myself and speaking to more and more researchers and clinicians, including yourself as a scientist, you've, you said that you really noticed the benefit of doing so (to learning more) about what it can be like to live with the epilepsy and the morbidities.
10:06 Helen Scharfman
Oh, yeah, and I have the good fortune to be able to travel to different meetings at major medical centres or meetings like the American Epilepsy Society or the International League Against Epilepsy where at the very least clinicians are in dialogue with people who are in the research laboratory using rodent models. And, sometimes at those meetings we get a chance to meet the people who actually have epilepsy. Those sorts of meetings are fantastic, I think, for all parties.
10:45 Torie Robinson
Also going to these events, I find this as well…It just shows the positive impact and potential of international collaborations, I think, across the world. It's easy for us all to get siloed in one part of a country doing a certain thing one way, but if you have people from overseas, different cultures, and stuff like that, coming in (as well as having the input of people affected by the epilepsy and morbidities), I think that can be really beneficial, right?
11:15 Helen Scharfman
Yeah, and I think one of the things that people don't understand is that some of the best science really happens because of the intercommunication between so many different factions! The best science is very rarely just done in isolation in a laboratory; the ideas come out at meetings and discussions among individuals where there's a lot of open discussion about novel hypotheses and novel approaches, and that needs to be fostered, I think.
11:55 Torie Robinson
Thank you to Helen for exciting us with her research and for being so empathetic and driven to help individuals and families affected by the epilepsies, and really valuing international collaborations in science! Check out more about Helen and her international work on the website t-or-i-e robinson.com (where you can access this podcast, the video, and the transcription of this episode) all in one place. And, if you’re new and you haven’t done so already, please do like and comment on this episode, and subscribe to our channel so that we can get way more people, around the world, learning about and understanding the epilepsies!
See you next week!
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Helen is a Professor of Child & Adolescent Psychiatry, Neuroscience & Physiology, and Psychiatry at New York University (NYU) Langone Medical Center. She is also an Investigator at the NYU Neuroscience Institute, affiliated with the Department of Neuroscience & Physiology. Her lab is located at the affiliate of NYU called the Nathan Kline Institute (NKI) for Psychiatric Research, where she is a Senior Research Scientist and her teaching and other service are at NYU.
Helen’s original interests were focused on plasticity in hippocampus and cortex and she primarily used electrophysiology in hippocampal or cortical slices as the approach. As a postdoctoral fellow, her electrophysiological skills increased and she began to focus on simultaneous recordings of connected neurons and vulnerable subtypes of neurons in the dentate gyrus such as mossy cells. After establishing her own lab, she expanded to address questions about other areas such as entorhinal cortex, but continued to study the dentate gyrus in epilepsy with adult neurogenesis of granule cells, brain-derived neurotrophic factor in granule cells, and the role of estrogens and androgens in dentate gyrus function. The lab also expanded its tools: they now conduct in vivo and in vitro electrophysiology; including video-EEG and use of silicon probes in vivo, diverse neuroanatomical approaches, behaviour, mouse models of disease, and optogenetics/DREADDs. Throughout this time they have developed new methods and models to circumvent technical challenges, and one example is the modified intrahippocampal kainic acid model of epilepsy used in the proposal.
During her career, Helen has built a body of experience in epilepsy, shown a track record of NIH funding and publications, and served in many capacities as mentor, reviewer, and editor for trainees, NIH training grants, NIH and other study sections, journals and books, and benefited from numerous collaborations both in the US and other countries. -
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