70 – Brain Banking and the Hispano-American Brain Bank for Neurodevelopmental Disorders

Veronica Martinez-Cerdeno, PhD

THIS IS A TRANSCRIPT ONLY:

0:07hello everyone and welcome to today’s webinar my name is Lauren Perry and I’m

0:13a syngap parent and operations manager at srf our presentation today is brain

0:19Banking and the hispanoamerican Brain bank for nerve developmental disorders I

0:24am the pleasure to introduce today’s speaker Dr Veronica Martinez sardenio

0:30Dr Martinez or Daniel is a professor of pathology at camp and campus scholar at

0:35UC Davis she received her BS in biology with a minor in general biology and

0:41major in laboratory medicine at compel tensei University in Madrid Spain in 98.

0:48um from 2002 to 2004 Dr Martinez cerdaniel completed postdoctoral training and developmental neuroscience

0:54at Columbia University in New York and also at The Institute for

1:00regenerative medicine development mineral Neuroscience excuse me and stem cells at UC San Francisco from 2004 to

1:072007. her final post her final year of postdoctoral training from 2007 to 2008

1:14was at UC Davis the MIND Institute to include an Autism research training program

1:20a recorded version of this webinar will be available on the srf website under webinars on the family menu and at the

1:27end of the presentation you will have the opportunity to get answers to your questions and we’d love

1:33to hear from you you can write the answers and the your questions in the Q a and we’ll answer and for those of you just joining us

1:39welcome and again our speaker today is Dr Veronica Martinez cerdanio and her

1:44presentation today is brain Banking and the hispanoamerican Brain bank for neural developmental disorders and it is

1:51now my pleasure to turn it over to you thank you so much for giving me the

1:56opportunity to be here with you today so I’m gonna talk a little bit about brain

2:02banking what it means and what we’re doing in our brain Banks so as you know

2:09when you study uh condition for example on autism right you can do different

2:15kind of research you can do research in the agnosis you can do research in treatment You Can Do genetics you can do

2:23epigenetics biochemistry and Anatomy for example but to do a most of these kind

2:30of research like genetics in human or Anatomy you need the brain the brain of

2:36the people who who suffer from these conditions right from these conditions

2:42or neurodevelopment and for that the way to obtain these brains is to have brain

2:47bags and this is a very difficult thing to do because where you need to have a

2:53group of people who is interested in helping research and then of course you need to Happy for signing for the brain

3:01bank and unfortunately some people need to pass away and then donate the brain

3:07to to be able to to contribute to their research so when I started as a

3:13researchers oh I really wanted to study them anatomy of autism this means how is

3:20the brain or the people with Autism how is different from those brains with

3:25people who are typical and my surprise was that first of all

3:33there there we didn’t know hardly anything about the rain without decent and second that one of the reasons why

3:41we couldn’t learn anything about this brand is because there was not enough Branch to study so I decided to start

3:48collecting brains to be able to do research in my lab I know that Lots also

3:54you know their labs around the world so I started here in the University of California in Davis collecting brain of

4:01people with Freddy legs that as you know is a demonogenic form of autism that is

4:08most common and related conditions for example

4:13Ataxia and also neurotypical brains because as I say you need to compare

4:19living with the condition with the neurotypical brain you don’t have neurotypical brain you cannot know what

4:25what is different in the in the neighboring with a condition so it’s very important that neurotypical

4:31people donate to so I study here and like to insert India so connecting this

4:38brain and then I I decided that in the

4:43case of difference without this and I wasn’t connecting in our brain in here in the United States in the area of

4:49California so I decided to spend my effort to do other areas and thanks to my connection with you

4:57know the researchers in Hispanic country I thought that maybe would be an idea to

5:03to ask for help to do this researchers and this is important one

5:09because we we are able to get brains from there but also because there are

5:15brains of underrepresented minorities are you not here in the United States it’s a country that is very diverse

5:24research is from white people so there is not so

5:32many Hispanic rain there is no black brains there is no other ethnicity

5:37surprises brain and I think that this is very important in case the differences that we have in the

5:45brain that has happened to to other medical conditions maybe maybe her between

5:53racism and vcp so we put too many several notes we’re working in Mexico we

5:59are working in Colombia and Puerto Rico and we we do is to to try to rather

6:08brainstead and this very bank that we call the Hispano American brain banana

6:14disorders has several functions one is brain banking that is the main functions

6:19but we also promote research among different sites in the in different countries we promote teaching so we do

6:27events or Bridge events or we teach people about the importance of brain donation and also about neuroscience and

6:34neurodevelopmental disorders and then we do um

6:39also our Rich activities and also education of students that work in the different Labs that are a a parallel

6:47this project and as I say we are working in California Mexico Puerto Rico Colombia and Dominicana and also we have

6:55people in the University of Pennsylvania Philippines

7:04of advices that are people who help us to to

7:10run the brain bank and in each country is divided into sections one is the

7:17uh section of pathology another is a section of clinics so the clinician and

7:23the pathology the directors have their own team and then when the clinicians do is to be in contact with the family and

7:29to identify donations and when the donations have been performed is then the pathology group that take over and

7:37it helps for Destruction and the preservation of the brain and this is how we work so

7:43we we have a donation right the the clinical the clinical group inform us

7:51about destination and we enter in contact with the family and then the first thing is we do a series of paper

7:57award where we get a an informed consent

8:02for the nation then we obtain the tissue but we also attain medical precautions

8:07they don’t know so we can correlate the scientific you to findings with the

8:14clinical history and the difference in dermatology on this person then we have

8:20a to confirm the donation by the coordinating donation group and

8:27when these when this when this group does is to fire pathologies of a dinner

8:32that is able to to extract the brain so everything is in the hospital when the person pass

8:39away on the funeral home or the body is transported to to a university whatever

8:45it can be removed so one important step is to find a person who’s gonna remove

8:51the brain to find a place when the the brain is going away remove and to take

8:57care of the transportation of the body and everything and once we remove the brain we do it in

9:03a very aesthetic aesthetic way so you cannot know that the brain has been extracted and once we had the brain we

9:09divide it in two hemispheres the right and the left and one is frozen and they already speaks and this is different

9:16ways to present the brain and depending how you present the brain you are going to be able to perform one kind of

9:22studies two other kind of studies for example for genetic studies for

9:41to fix the brain you need to to put it in a solution that is Gonna Keep the

9:48brain in the same way that you that it was when you obtain it and then then you

9:53you can do your style so we use the brains for our own

9:59research in my Laboratories from the core from the site so the in

10:06the rainbow but we also donate a tissue to everywhere and free of course and we

10:13have collaborated with all many countries in Europe with Africa Australia Israel so we really the same

10:20we really disseminate our Diesel and this when you donate everything this

10:26brain is not gonna be included in one project but it’s going to be included in many projects why because it’s research

10:35group study different parts of the brain so if for example if a research group study the prefrontal Cortes we are going

10:41to served within a little preference on the brain is going to be kept in the

10:47rainbow for the future studies so one brain one donation can be part of many

10:52many many projects and not only at the moment

11:01you will have the opportunity to participate in this new project so when we had the brain we’ll preserve

11:09we do look when we call it postmortem diagnosis confirmation so since we are getting brains from the whole United

11:15States and also from other countries the way that we had to diagnose the disease

11:20is different for example in the case of autism are not the same the behavioral

11:26tests that are performed in Mexico that they are performed in California so what we need to do is to unify the agnosis we

11:32have the diagnosis we but we also do a wooden diagnosis and

11:38we do this with a test that is called the ivr or Autism diagnosis interview realize that is a series of question

11:45around 150 questions that are performed to to to the parents or the civilians of

11:53the family or the caretakers and with this we we unify the the diagnosis and

12:01this is so once we have a the brain pizza and a

12:08clinical history or complete this is the resource that we offer and when I research it approaches and they asked us

12:16as for tissue what we do is first to ask them about what kind of research they

12:21are going to do and when we are sure that it is like a proper a petition and

12:28real researchers we approve the project and then we donate the tissue and then we keep in contact with investigator

12:35because we know to talk and we want to see how they are doing if they miss

12:40anything else if and and be sure that the tissues in for the research and we

12:48are aware of the results of the research so and that’s in really how we work and

12:54today since we have a some time what I wanna is to use an example of a project

13:01that we can perform with tissue in this research and today I’m gonna talk about the neighboring with autism so to give

13:08you an idea how this research is performed so in the in the cerebral Cortez on the

13:18brain in in humans there is excitatories and inhibitory signals and this need to

13:25be in a balance and this balance is necessary to keep the proper functioning on the brain so we know and that is

13:37and we know this because when we do an electron encephalogram an EDD the waves

13:43that you see there are there and these waves are the summative of all the signals that are taking place in the

13:49rain in our event time so then what can be wrong when this balance is out there

13:55it can be that the sitatories

14:07well it will be same because the number of cells are excitatorium chain or

14:14because they are there the same number but they are functioning different or probably both both of the on the cases

14:20so how we research that so we take the average this is one of the donated

14:25brains and we look in the brain the area of Interest this is the area that we want to study and the brain is divided

14:32in many areas around 150 and the areas that we have studied at Ariana

14:3847 and we told us areas because there are Alias that we know are relating with

14:43functions they are instead of working on a special

14:50memory when we

14:58sign language so what we do is to cut our Slice on the

15:03brain that you can see here on the side when you have our ideas that we want to study area 9 45 and 47 and then we take

15:12these little areas and we cut them we got a little block and we put the Block

15:17in a machine that is able to come very thin slices of green and when I mean

15:23finish really really um there is in there like they can be

15:30like 20 negro meters or 10 micrometers steel that is like a portion of Family

15:36Matters also very very thin and this allows them to to detect proteins and

15:43this is how we see when we put this slide in the microscope this is what we see and in this case and when we

15:51understand is remember that I told you that the cerebral Cortez

16:00the signal and then we have inhibitory neurons that we have a

16:07um a negative signal okay so we know that you know this studies that we have

16:14done and other people we have seen that there is more excitatory neurons but nobody has every study inhibitory nebros

16:21and that’s why we decided to study this so with this and this inhibitory neurons

16:26or internal Circle you can see that they are live off here in different colors so there is different kinds they just have

16:33to do any kinds of Inter Milan so since there is so many when we need to group them in three groups and give and we

16:41design a method so each group that you can see has a different color and we can call in the pin group and then glue and

16:48the brown groups of intermed and then what we did this in different regions of

16:54the Cortes of different patients both with autism and neurotypical then we quantify the sense

17:01and we do this with um with a microscope that has is connected

17:08to a computer so this is a reconstruction this is a piece of Cortex like very much that I showed you before

17:14and then in the microscope we are able to to map the different kind of cells in

17:20this case part of a leaping the brown and the blue

17:26and this is how you see the different areas but this is 47.99 in the control

17:32neurotypical and in the episode without this sound and then we count them and

17:37when we come then we saw here you can see in this graphene this is the control cases there is around 10 and 10 cases of

17:45control and increases of autism so you see the control has an amount of sense for your case and follow this and the

17:52same but in general when you apply the statistics you see that there is a significant decrease of a the number of

18:00pink cells in this case and in autism when comparative

18:10so you can see here in this Graphics that the decreasing the number of pink

18:16cells and in this case they are called Parable you mean cells because I says that contain this protein per volume so

18:23this Parable women says that we see in pink in this case they are decreased into 60 or 70 percent in the area 46

18:31around 31 40 percent in area 47 and around 40 percent in area 9. so there is

18:39something different and it’s very unique because we are refounded in in severely

18:45found differences for this sets for the Barbarian sets but no for the other cells that we study

18:51and one investors what are these Parable you means what this programming sets are

18:57called Chandelier and they are called chandelier because they look like a channel on the ceiling like this one here in the

19:04image this is the area cell this is

19:12so the interesting thing in Mouse you can apply techniques that you cannot apply in human because the tissue now

19:19we’re having human Sports Martin but we can label in their life animal in Mouse

19:26so we always want to see more be able to

19:31apply more techniques in animals are not human and they don’t have the same brain so both animal studies and

19:39lots of human styles are very important to understand each condition so as I was saying this is a chandelier in human and

19:47using green and in red different person they say so this is very interesting

19:53because all the inter neurons in in in the cortex normally they see maps so

20:01they they send the signal a foreign

20:59so this cell is very important this is a cell is very important also because

21:05while at regular is contacting and one or two pyramidal says this internet is

21:13contacting like 200 300 kilometers so it’s like one single neuron has a huge

21:19effect in many other respiratory cells so you can imagine if you lose one and in this chandelier said you are going to

21:27be losing the control of it many many pyramid assets and this is just when I see you a real picture of a Tandy lesson

21:34in a human and a reconstruction and well the Chinese is an action

21:40and the action transmit the signal that is very very big and different from the

21:46other side and they have these terminations that are in red here and you can see here also in C and D you can

21:53see determinations in human and high high magnification and when you look at

21:59high magnification you see that there is leadership boards and these balls is when the signal is transmitted so when

22:08we discovered when we are studying uh when we study this boxing in human is

22:16that in in the cases of the people that have autism this this boss

22:23and this means that in the other less likely to

22:29transmit a signal so so far we have seen that there is

22:44and you can see here in the graphic and depicting the size of the different

22:51buttons or bolts in in each of the cases and a little dot is a case Okay so

23:02or the thing that we study is okay we have these cells and they synapse into

23:07the pyramidal cells and they send a signal and the signal is a neurotransmitter so it’s a protein that

23:13is is released and then binds to to a receptor

23:19in the Target cell so this receptor it’s called

23:24and this in the in the action on the pyramid acid so we study the monody

23:30receptor and we saw here is neurotypical and this is how a case with

23:36autism looks like in yellow so when we say that is decreased also in cases with autism and

23:44you can see how how it looks like here and the different amounts of literacy

23:51so this is an example of how we can find an atomical changes in the brain using

23:59these tissues that are donated so the summary safaris that I tell you that we find have fun let’s change the lessons

24:06that are inhibitory cells and our cells that are synapsing in excitatory cells they are

24:13since they are inhibitory they are like inhibiting the

24:18excitatory signal from the pyramidal cell and therefore the brain is getting super excited that is what is happening

24:25in autism exciting we also find that the it’s an illicinative butas is the place where

24:32the synapses of the signal takes place at this and we also found that the amount of

24:38Labor reserto that is The receptors

24:44secreted by the changes so and one other thing that you can do

24:51remember I told you when you donate everything we have the brain and then we

24:56have the clinical history Associated so one thing that you can use to take all this data that we have collected the

25:03data that I give you is everything that we found but as an example but we can

25:08take all this stuff and we can correlate it with the behavior on the passion and for that we remember that I told you

25:15that we need the idea that is a test that you do to the parents of the donors and and in a case of audition

25:22we still look for for three domains one the four domain is just that the centers

25:30need to appear before the 30 seconds 36 months of age but for then there is only

25:36three domains and BNC they they is a series of questions that are measured in

25:42qualitative and normalities in reciprocal social interaction the V is looking for a normalities in

25:48communication and the C is looking into restricted repetitive and stereotype

25:53stereotypic Behavior okay and then

26:07for example a wise failure to use non-verbal Behavior to regulate

26:12social interaction and each should domain in this case A1 it has several

26:18questions that in these cases question 50 51 and 57 and the same for all the

26:23demise for all their pseudo minds and there is a total of 150 questions so the

26:29parents they just answered all the questions and we put together they don’t mind and then what we do is we have a

26:35statistician who takes all the anatomical data and histological data on the clinical data and that’s a

26:41statistical correlation and I’m gonna tell you we have found related to the data that I saw you before so what we

26:49found is that the channel decrease the decreasing number is

26:55repetitive behaviors that are typical in autism and here and you can see the

27:01numbers like I saw you before the the Reconstruction of the cortis with

27:08different type of cells right and you can see here how the neurotypical case

27:13of control looks like the Cortes you can look at the parable inserts are the the blue cells that you can see them here in

27:19the low panel and you see when the the value C3 then is and they call it and

27:26they don’t mind free so domain three C3 you see how the number of cells look

27:33like when C3 equal to two the number doesn’t decrease when a c equal to three

27:39or four the number of the the sense decrease one and these the C3 is the

27:45pseudomide that is related to a stereotypical motor manalism so we have

27:50able to link this time the decreasing the type of cell to absorb the minor

27:56behavior so that the mind will be the restricted repetitive behavior and National domain will be the motor what

28:03is for motor manalism okay so you can do a similar analysis with all the

28:08conditions that U.S tally and like this you can assign a behavior to an

28:14anatomical alteration and this is similani so that when we do

28:19an experiment we always do the experiment in different ways so in the previews we will continue number of

28:26cells in this one we are continuous or cartridges and booters that is the place

28:31where the synapses takes place and we see the same we see using different methods and different results but they

28:40are related we find also that there is a correlation with the the C3 and also

28:45this research is done by different not only different method but also by different researchers so we are sure

28:52that our results are real and they don’t have any bias okay and then we see here for example the Reconstruction is making

28:58other way the amount of cartridges in neurotypica I’m going to see three sequence zero two three and four the

29:05number of cartridges degrees so this is indicating it’s a different way to arrive to the same result so so the

29:14result now we found is that that I do know our decent sometimes comes together

29:19with intellectual and disability so we found that the histology or the anatomy

29:25is different in the cases that only have autism the cases that have autism with intellectual disabilities like a

29:31different condition so so far we also we are we were Stein autism and you know

29:37this and we saw that only the the Barbarian cells will decrease the chandelier sets but when we study the

29:44cases that in addition to autism have intellectual disability we see that in addition to the parvarium incense other

29:50type of inhibitory cells are also decreased so as you see here they said something depicted when before I show

29:57you I think being blue and and we just get in different color blue

30:03black and white so anyway the point here is that all the cells are decreased and this is where it produce the

30:10intellectual disability decrease

30:18so I think that when I have shown you in this short talk is just a channel

30:24Essence and decreasing autism and that these degrees is related to if his uh generalized so

30:34in addition to the channels are decreasing number and this is related with intellectuality and we

30:41also saw that they decrease in Chinese related to a stereotypic motor behaviors

30:47and this is very interesting because in a schizophrenia there is a condition that shared this the same

30:55um Behavior we have also seen other researchers has seen that there is also adequacy in general assets so I think

31:02that this is interesting so overall I show you a little recover inbound works

31:08I show you that the an example of a

31:13study a histological studies and

31:20and also how this allows you to relate it to a stereotypical behavior and when

31:25this kind of research progress because we have more tissue and since we when you have more tissue you have more reset

31:32more research projects and even more researchers that dedicate themselves to study this this kind of problem then we

31:39will we will be able to to discover things that will help us to to understand the condition and to

31:46establish treatments and also to to to try to

31:53do do um yes to establish treatments and to

31:59and surgery I I’m lucky enough in the world to to prevent and to prevent

32:07comorbidities Associated to the disease and I just want to say thank you to my

32:12team this is my team that are the people who made this this kind of studies possible uh thank you so much everybody

32:19thank you thank you that’s great so much um

32:26we have Dr schlecht here he has his hand raise if he wants to ask a question I let you speak Hans if you want yeah

32:33thanks very much Lauren and thank you Dr Martinez so um

32:39I’m a big proponent of brain donation I realize it’s not the most uh

32:49uh palatable subject I think it was one of the strangest experiences I had in

32:54life to sign up you know my son going back now five years ago

33:02for his donation and then more recently my own donation so that we can go as a

33:08pair um and one even before my son’s diagnosis it

33:16was the New England Journal of Medicine paper on an Autism

33:22brain pathology study I guess it’s probably from 10 years ago now where you know they demonstrated sort of

33:30the the cortical um disorganization within the brains of

33:35of kids and adults with autism and it’s really impressive because you know that

33:41was at least and if a way to tie together

33:47what happens in humans to what is seen in in the animals and the animal models

33:52of autism so it was really an impactful paper and brain donation made that

33:57possible yeah um you know for the late person

34:03I don’t know if you touched upon it I had a meeting but missed it in the first few minutes but um

34:11I think people are worried that there could be you know an inability to have their normal funeral practices if they

34:20donate a brain can you make a comment on that you know

34:25it is is an open casket still an option uh yes yes I mean when when there is a

34:33donation the donation is done very fast and most

34:38of the times people call us before the person before the person pass away so we

34:44are ready and this is very important because when the brain dies

34:49you need to preserve it as close as possible to how it is in life because

34:55you know you start losing properties and it’s more difficult to the study so the

35:00procedure is done very fast and is very aesthetic so you cannot see absolutely

35:06anything I mean you cannot know that the donation has taken place and all the on

35:12the process after that is it’s normal so the people who done that is very professional and normally there is not

35:20any kind of chain in time or foreign

35:27goes through I mean it’s very difficult it’s it’s a very difficult decision and

35:33we understand and that why it’s so difficult to have brains for donation but it doesn’t affect in any way the

35:39process definition or or any of that

35:45fantastic did you say how um how soon you needed

35:50them I might have missed that detail we need it as soon as possible

35:55the person we know that is when I pass away and we are ready and we collect everything two hours after death you

36:02know other things is not possible mainly in these countries in other countries in California is faster because we have all

36:09all this infrastructure and technology and people who can do that but in other

36:15countries perhaps it take longer time anyway every time that is a donation we

36:21try to do the fastest as possible but if it’s not very fast we still get the brain because even if we cannot apply

36:27all the techniques we still can do some and we assume invaluable the the

36:33donation I mean everybody brain is like a threshold so so this is we try to do

36:39our best yeah oh do you have any other question times at

36:45all or any comments no I’m all set it’s just fantastic also for an Outreach to

36:50you know the non-traditional research patient right so you know when when I

36:56was practicing HIV and infectious diseases medicine most of the papers were

37:0390 men and 90 white men exactly and and

37:08that did not reflect the patients I was providing care to in downtown

37:15Philadelphia or Springfield Massachusetts or Boston pretty close but not

37:22necessarily and there has to be a level of diversity to science so that there is a

37:31generalizability to the patients that we see so I I give you all the credit for

37:38putting in what’s probably an incredible amount of effort to make this happen and

37:44involve a community that is not part of the the routine and research yeah

37:53and white like 90 and I don’t know why I think that the main brains are donated

38:00by their wives so they were kind of applying to donate but they may not least likely to donate so they don’t

38:07donate their wives brains this is the only thing that I can think while they deciding them different

38:13ethnicity makes sense because it’s related with with access do not do this

38:19information and also in the Hispanic Community there

38:25is still a lot of um it’s still very hard for them to

38:30donate due to to culture at least in the Hispanic population so that’s why we do

38:35a lot of our Rich programs trying to educate and trying to give more information about how important is this

38:43and is difficult in the United States but mostly figured in the Hispanic countries and in the Hispanic countries

38:51where we are the obtaining is now the Hispanic country but we are in the Dominican Republic and there is a lot of

38:57African-American countries and also in the north of Colombia so we have a population that also donate

39:04African-American Brands but as I say we try to do as diverse as possible work

39:10and not always work so we are very slow but at least we are trying is the message we are trying

39:19super congratulations thank you thank you Dr Martinez this has been very

39:27interesting um I have a couple of questions before we finish up

39:33um as far as Outreach goes I know this is obviously one channel that that’s important but

39:38what is your what are your traditional Outreach channels

39:45in Mexico we do a lot of Outreach to the general population in fairs and in in

39:55any kind of gathering public gathering in the university in associations of

40:02different conditions so this is the kind of things that we do and also we do a lot of teaching in schools our

40:09neurodevelopmental disorders and within the how we take this one sometimes on human tissue to teach

40:16them do not do so then the diesel and we’re spending why it’s important to donate so we do at different levels

40:23and once you have a donation and obviously the medical records are you

40:30looking at autism spectrum disorder as a whole or if they have a specific

40:35diagnosis within that then you’re categorizing we are looking at the symptomatology

40:43really I always like to say there is no work conditions but it’s many under the same name so like each case is different

40:51it’s not so much like we do fragile experience is a motivation in a single Gene so it’s all the patients are more

40:58similar but in autism there is such a various symptoms a person can be very

41:03functional functional or no verbal or no social at

41:09all so to me when there is such a difference in the in the level of symptoms it’s like a different different

41:15thing than you are that you are studying so modern for the agnosis we look at the diagnosis of course but we mainly look

41:22at the the different type of symptoms specific

41:27soup symptoms and the level of them we pay special attention to intellectual

41:33and disability to escape to to epilepsy because a lot of places without this

41:39angles with epilepsy are some of the symptoms that we are interested in okay wow thank you so much that’s

41:47wonderful we really appreciate appreciate your time coming on today and

41:52um thank you bye [Music]

41:59perfect