Good afternoon.
All right.
What is autism?
What is its prevalence?
And what are its symptoms?
And its causes?
And the neurobiological and molecular routes that trigger it?
What if I told you that a small worm
Can you have most of the answers to all these questions?
All right.
The word autism is currently heard very often
and is that in recent years
There has been an increase in cases worldwide.
Above all, in Europe the figure has been reached, quite significantly,
of up to 14 cases per 1000 people.
Autism is one word,
but it encompasses a set of neurodevelopmental diseases
which have two characteristics in common,
or two main characteristics:
One of them are deficits in social communication
and another of them are restricted interests
and repetitive patterns of behavior.
To these symptoms are added other accessories such as:
the presence of anxiety, intellectual disability,
alterations in language, also aggressiveness.
What are all these alterations due to?
The bad news is that there are many causes that trigger
these alterations and, therefore,
we say that autism is a multifactorial disease.
What does it mean?
That in a range of diseases due only to genetic causes,
like hemophilia,
until only due to environmental causes,
such as a car accident or a gunshot wound,
Autism is found throughout that range.
And how do we know
that there are genetic causes that trigger this disease?
Well, in a study of the incidence of autism in twin brothers,
that have identical genetic information,
with respect to twin brothers, who do not have it,
it was seen that this incidence was much greater in twin brothers.
That indicated a high genetic component of this disease.
In fact there are already more than 800 genes associated with autism.
And there are already more than enough tests that make these genes
encode proteins involved in the neuronal synapse.
And what is the neuronal synapse?
Well, the neuronal synapse
is the functional union between two nerve cells,
They are called neurons.
Well, if we were to raise
the study of these neuronal synapse proteins in humans,
the incredible difficulty of the human brain would make that study very, very difficult.
But in biology,
it is not necessary to understand each and every one of the components
of the human brain to understand its functioning;
because those components
we share them with other simpler organisms
which are what we call “model organisms”.
As you can see,
among these model organisms, we find this little worm,
that I showed you at the beginning of the presentation,
and that is called “Caenorhabditis elegans”.
This is the worm that we, in our research group,
We have used to study the biological mechanisms of autism.
And you will ask, what can it have to do with
a small worm with autism in humans?
As well,
the human brain is made up of 100 billion neurons.
Nevertheless,
the nervous system of this worm is made up of only 302 neurons
and also, its structure and its connections between them,
they are perfectly described and perfectly studied.
Other advantages offered:
because it is a very economic system, relatively;
It is small, so it is quite manageable;
it reproduces quickly,
in three or four days is able to put 200 eggs in large quantity,
is able to reproduce in large quantity;
They are also transparent, with which they are easily observed in the microscope;
Your genetic sequence is completed
and the most interesting thing is that 74% of human genes
they have homologous genes in this worm.
What does this mean?
Well, they share, they have a very similar sequence
and therefore they will also develop very similar functions.
In the end it will turn out that we are not so different from the worm.
In our group, which is called Genetics and Behavioral Diseases
one of the study lines
has been the analysis of synaptic proteins associated with autism.
As we have done?
Well analyzing patterns of behavior of worms
that lacked those proteins, one or several,
and we compared it with worms that do have those proteins.
To the first
We have called them mutant worms, or we call them mutant worms,
and the second wild worms.
One of the behaviors that we have studied has been the response
to high concentration barriers of a sugar, which is called fructose.
In the case of the wild worm we can see, it has already been seen,
that has detected the barrier of this sugar and has regressed.
However the mutant in one of the synaptic proteins,
the moment you reach the barrier of high concentration of fructose,
He does not detect it and continues on his way.
It does not change.
All right.
Another of the behavior patterns that we use
is the analysis of the path of the worm in the culture plate where we grow it.
These are the plates.
Well, the wild worm is able to explore the plate,
more or less, to some extent.
This white trail is the trace of the worm that leaves the worm when moving.
One of the mutants, in one of the synaptic proteins,
he explores it with great intensity and yet another mutant,
in another of the proteins studied,
I was not able to explore the plate.
He stayed in the center, making movements about himself,
type well, as shown here, in this image.
Another behavior Another example.
For example, the study of the locomotion rate.
And here what we measure is the number of undulations made by the worm
in its movement with respect to the unit of time.
And this behavior in turn has two sub-responses,
one dependent on dopamine and another on serotonin.
Dopamine and serotonin are two neurotransmitters
And neurotransmitters are the molecules responsible for transmitting information
from one neuron to another, so that if this is a synapse,
the neurotransmitters would be those little dots, bright,
which are located in the synaptic space.
Well, the mutant worms, in some synaptic proteins,
showed alterations in the rate of locomotion
and the most interesting thing is that when we treat these worms with some drugs,
which are methylphenidate and Prozac,
that are curiously used to alleviate symptoms in autism,
with them we managed to partially cure these alterations.
Well, if we go back to the slide of the incidence of the disease
in twin brothers with respect to twins
We can find that not 100% of the twin brothers had the disease.
What does that imply?
Well, there must be other factors that trigger the disease,
which in this case are environmental factors.
Many environmental factors have been described,
such as vaccines, infections during pregnancy,
exposure to certain drugs during pregnancy too,
but there is one that has become quite important in recent years
And it has been the high levels of a hormone called testosterone during pregnancy.
Well, we in the laboratory have verified that this hormone
has been able to alter the functioning of the worm’s nervous system.
Likewise, what we have done has been to add testosterone to the medium
and we have analyzed his other behaviors,
as the response to a mechanical stimulus of an eyebrow hair
or the movement of this structure, which you see here, which is called pharyngeal.
And you will ask, what are you doing now with all this data?
Well, like all these behavior routes
they have all their molecular routes, all molecular mechanisms
and neuronal very well described in the worm, all this will serve us
to be able to integrate all this data and, in the future, to be able to extrapolate
these results to humans and thus be able to explain the causes
or the mechanisms that trigger autism.
And it is that, only knowing the causes of a disease,
we can establish therapeutic strategies,
diagnostic, and even preventive.
And just to say, there are many questions to ask
and many answers to give, but we will keep moving forward.
We will continue believing.
Thank you very much.
(Applause)
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