The smart mouse with the half-human brain

Mice with human glial cells

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The smart mouse with the half-human brain

#1  Postby GrahamH » Dec 02, 2014 10:29 am

http://www.newscientist.com/article/dn2 ... H2Ri8nHCSp

Goldman's team extracted immature glial cells from donated human fetuses. They injected them into mouse pups where they developed into astrocytes, a star-shaped type of glial cell.

Within a year, the mouse glial cells had been completely usurped by the human interlopers. The 300,000 human cells each mouse received multiplied until they numbered 12 million, displacing the native cells.

"We could see the human cells taking over the whole space," says Goldman. "It seemed like the mouse counterparts were fleeing to the margins."

Astrocytes are vital for conscious thought, because they help to strengthen the connections between neurons, called synapses. Their tendrils (see image) are involved in coordinating the transmission of electrical signals across synapses.


Do Your Glial Cells Make You Clever?

http://www.sciencedirect.com/science/ar ... 0913000581

Few neuroscientists would deny that their subject has, by and large, been a neuron-centric one, with the neurons fulfilling the primary functions of the nervous system, helped along by the surrounding glial cells. Indeed, this notion of glial subordinance is encapsulated in the very term glia, which, translated from the original Greek, means “glue.” This is an understandable position—it has been apparent from the time of Galvani in the eighteenth century that the nervous system is bioelectrical and that electrical impulse conduction by nerve fibers is central to brain function. Moreover, an undoubted correlation exists between brain size (with its accompanying complexity of neuronal connections) and an increasing sophistication of neurological function, seemingly culminating in the human brain, with its staggering 1015 synapses. Yet a growing body of data elevates the role of glia beyond that of simply gluing neurons together, and makes a concerted challenge to the centuries-old dominance of the idea of neurons as the aristocrats of the nervous system. In this issue of Cell Stem Cell, Han and colleagues report a remarkable study that assigns a role of previously unexpected importance to glial cells in higher cognitive functions, such as learning, that will come as a surprise to many in the neuroscience community
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Re: The smart mouse with the half-human brain

#2  Postby Made of Stars » Dec 02, 2014 10:48 am

Now if only we could do the same with some humans...
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Re: The smart mouse with the half-human brain

#3  Postby Bubalus » Dec 02, 2014 11:24 am

Made of Stars wrote:Now if only we could do the same with some humans...

:lol: :lol: :lol:
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Re: The smart mouse with the half-human brain

#4  Postby Animavore » Dec 02, 2014 11:27 am

The first step towards The Planet of the Mice.
A most evolved electron.
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Re: The smart mouse with the half-human brain

#5  Postby GrahamH » Dec 02, 2014 11:40 am

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Re: The smart mouse with the half-human brain

#6  Postby The_Piper » Dec 02, 2014 11:58 am

Well, I wouldn't have to trap those mice, just tell them, in plain English, to use a litter box, and stay out of the silverware drawers and we're cool. :mrgreen:
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Re: The smart mouse with the half-human brain

#7  Postby trogs » Dec 02, 2014 12:32 pm

Made of Stars wrote:Now if only we could do the same with some humans...

You joke, but there's actually some of us more-or-less doing this. :-)
http://en.wikipedia.org/wiki/Stem_cell_ ... ord_injury

Next step: figure out how to mass-produce iPS --> glial cells!
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Re: The smart mouse with the half-human brain

#8  Postby kennyc » Dec 02, 2014 1:01 pm

"These creatures you call mice, you see, they are not quite as they appear. They are merely the protrusion into our dimension of vastly hyperintelligent pandimensional beings.”


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Re: The smart mouse with the half-human brain

#9  Postby DavidMcC » Dec 02, 2014 3:19 pm

I suspect that glial cells help make you smart only indirectly - by preventing your neurons from dying prematurely. After all, a massive loss if neurons, caused by glial cell failure, would make you stupid.

EDIT: The reason that people with large areas of their cerebrum removed can function normally is the massive redundancy of neural circuits, which in turn is for protection against individual neuron deaths, that occur all the time.
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Re: The smart mouse with the half-human brain

#10  Postby GrahamH » Dec 02, 2014 4:00 pm

DavidMcC wrote:I suspect that glial cells help make you smart only indirectly - by preventing your neurons from dying prematurely. After all, a massive loss if neurons, caused by glial cell failure, would make you stupid.

EDIT: The reason that people with large areas of their cerebrum removed can function normally is the massive redundancy of neural circuits, which in turn is for protection against individual neuron deaths, that occur all the time.


I think there is more to it that David. After all, the researchers found proliferation of human glial cells, not changes in mouse neurons. Mice aren't less intelligent than humans because their neurons die quickly. The transplant can't make them smarter than usual by making thier neurons live longer unless mice lose neurons at really fast rate. Is that the case?

Did you read my second reference: "Do Your Glial Cells Make You Clever?"
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Re: The smart mouse with the half-human brain

#11  Postby DavidMcC » Dec 02, 2014 5:51 pm

GrahamH wrote:
DavidMcC wrote:I suspect that glial cells help make you smart only indirectly - by preventing your neurons from dying prematurely. After all, a massive loss if neurons, caused by glial cell failure, would make you stupid.

EDIT: The reason that people with large areas of their cerebrum removed can function normally is the massive redundancy of neural circuits, which in turn is for protection against individual neuron deaths, that occur all the time.


I think there is more to it that David. After all, the researchers found proliferation of human glial cells, not changes in mouse neurons. Mice aren't less intelligent than humans because their neurons die quickly.

Of course not, but the primary function of glial cells is to maintain neurons, not to do their job for them.
The transplant can't make them smarter than usual by making thier neurons live longer unless mice lose neurons at really fast rate. Is that the case?
...

No, but living longer is only one of the benefits to neurons of having glial cells. They also enable them to work better, but that is not the same as doing their job for them.
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Re: The smart mouse with the half-human brain

#12  Postby Willie71 » Dec 02, 2014 5:53 pm

Glial cells are being looked at in relation to ADHD and depression, if I remember correctly. It seems that their purpose was not fully understood, or even partially understood for that matter. Its an interesting time in neuroscience.
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Re: The smart mouse with the half-human brain

#13  Postby DavidMcC » Dec 02, 2014 5:55 pm

... I did read the text you quoted from your second reference, but that is consistent with glial cells simply improving the function of neurons, not performing that function for them. I think it has been known for years that glial cells don't merely offer mechancal support to neurons.
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Re: The smart mouse with the half-human brain

#14  Postby DavidMcC » Dec 02, 2014 6:00 pm

Willie71 wrote:Glial cells are being looked at in relation to ADHD and depression, if I remember correctly. It seems that their purpose was not fully understood, or even partially understood for that matter. Its an interesting time in neuroscience.

You are talking about brain conditions that would obviously require glial cells to fight, because the glial cell function of maintaining neurons against stresses is exactly the function that would be expected to be important against that kind of condition. Therefore, it is strange, IMO, if no-one saw the connection, unless they subscribed to the well-out-dated "mechanical support only" model.
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Re: The smart mouse with the half-human brain

#15  Postby GrahamH » Dec 02, 2014 8:15 pm

DavidMcC wrote:... I did read the text you quoted from your second reference, but that is consistent with glial cells simply improving the function of neurons, not performing that function for them. I think it has been known for years that glial cells don't merely offer mechancal support to neurons.


This bit?

Science Direct wrote: OPCs can generate action potentials, previously thought to be the sole preserve of neurons and a key function that distinguished them from glia (Káradóttir et al., 2008). This OPC property strongly hints at important physiological functions in the normal CNS in addition to their role in the regenerative process of remyelination (Zawadzka et al., 2010). (4) Astrocytes, a diverse population of cells with multiple functions, maintain and sculpt the synaptic contacts on which CNS function depends (Ullian et al., 2001). All of these relatively recently revealed properties of glia demand an updated concept of brain function in which neurons and glia work as equal partners, interacting in a mutually dependent manner. But what evidence is there that glia might be in the driver’s seat?

Human astrocytes are larger and have a greater morphological diversity than those of rodents, with distinctive subtypes uniquely present in hominids. Thus, there is a correlation between more complex information processing and astrocyte complexity that might be causal. In their current report, Han and colleagues test this theory using an ingenious stem cell (or more specifically progenitor cell) -based approach. Previously, the laboratory of Steven Goldman (one of this study’s senior authors) produced adult mice with a chimeric CNS consisting of mouse neurons (and oligodendrocytes) and human astrocytes and progenitor cells, achieved by engrafting human glial progenitors into the neonatal mouse CNS (Windrem et al., 2008). Large regions of the CNS in these mice, including the hippocampus, consist of mouse neurons surrounded by human astrocytes, thus providing a configuration with which to compare with wild-type mice.
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Re: The smart mouse with the half-human brain

#16  Postby Willie71 » Dec 03, 2014 3:19 am

DavidMcC wrote:
Willie71 wrote:Glial cells are being looked at in relation to ADHD and depression, if I remember correctly. It seems that their purpose was not fully understood, or even partially understood for that matter. Its an interesting time in neuroscience.

You are talking about brain conditions that would obviously require glial cells to fight, because the glial cell function of maintaining neurons against stresses is exactly the function that would be expected to be important against that kind of condition. Therefore, it is strange, IMO, if no-one saw the connection, unless they subscribed to the well-out-dated "mechanical support only" model.


This hasn't been the focus of psychiatry for some reason. I seem to remember first hearing about the implications glial cells possibly have in psychiatry in 2010, or 2011. I'd have to look back in the journals, but the year isn't that important. Psychiatry is due for a major overhaul. The diagnostic practices are being outgrown by neurological findings, and many psychiatrists still have difficulty assessing symptoms to narrow down probable neurotransmitter involvement. Many are still throwing SSRIs at almost anything, ignoring dopamine and norepinephrine, outside of schizophrenia or bipolar I.
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Re: The smart mouse with the half-human brain

#17  Postby Made of Stars » Dec 03, 2014 6:57 am

Or depression and anxiety, where SSRI/SNRIs are commonly used.
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Re: The smart mouse with the half-human brain

#18  Postby DavidMcC » Dec 03, 2014 5:49 pm

Graham's Science Direct quote wrote:All of these relatively recently revealed properties of glia demand an updated concept of brain function in which neurons and glia work as equal partners, interacting in a mutually dependent manner. But what evidence is there that glia might be in the driver’s seat?

What do they even mean by "equal partners"? I seems ambiguous to me. For example, in the human retina, if you take out the retinal pigment epithelial (RPE) cells, you quickly go blind, because the RPE cells (which wrap themselves around the photoreceptor cells) perform chemical reactions that are essential to the photoreceptors' function, but that does not mean they detect light. However, they could be said to be "equal partners", as both types are essential to vision, just as different links in a chain are "equal partners".
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Re: The smart mouse with the half-human brain

#19  Postby Willie71 » Dec 03, 2014 8:51 pm

Made of Stars wrote:Or depression and anxiety, where SSRI/SNRIs are commonly used.


Most people in mental health still believe serotonin is the major player in depression, but atypical depression, seasonal affective disorder, bipolar II, and some components of OCD are more affected by dopamine. If ADHD is comorbidities, then the probability of a dopamine disorder being present significantly increases. The biological depression we see in teens, often between 12 and 14 is quite often atypical. SSRIs and SNRIs have been shown to increase the probability of developing hypo mania and cycling, yet most psychiatrists go with an SSRI first. Norepinephrine seems to be a secondary neurotransmitter in most conditions. I can't think of any off of the top of my head that are primarily caused by norepinephrine.
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Re: The smart mouse with the half-human brain

#20  Postby GrahamH » Dec 03, 2014 9:49 pm

DavidMcC wrote:
Graham's Science Direct quote wrote:All of these relatively recently revealed properties of glia demand an updated concept of brain function in which neurons and glia work as equal partners, interacting in a mutually dependent manner. But what evidence is there that glia might be in the driver’s seat?

What do they even mean by "equal partners"? I seems ambiguous to me. For example, in the human retina, if you take out the retinal pigment epithelial (RPE) cells, you quickly go blind, because the RPE cells (which wrap themselves around the photoreceptor cells) perform chemical reactions that are essential to the photoreceptors' function, but that does not mean they detect light. However, they could be said to be "equal partners", as both types are essential to vision, just as different links in a chain are "equal partners".


It's there in the quote David.

They make several points. Hers is one:
OPCs can generate action potentials, previously thought to be the sole preserve of neurons and a key function that distinguished them from glia

So OPCs and neurons both generate action potentials.
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