Recent replies to "Astrocytes in Human Evolution"

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Wed, 14 May 2008 11:54:50 -0000

Another Abstract that the Dean sent me:

http://www3.interscience.wiley.com/journal/117934900/abstract
Glia 56(7):699 – 708, 2008
DOI 10.1002/glia.20642
All vertebrates started out with a glial blood-brain barrier 4-500
million years ago
Magnus Bundgaard, N. Joan Abbott

All extant vertebrates have a blood-brain barrier (BBB), a specialized
layer of cells that controls molecular traffic between blood and
brain, and contributes to the regulation (homeostasis) of the brain
microenvironment. Such homeostasis is critical for the stable function
of synapses and neural networks. The barrier is formed by vascular
endothelial cells in most groups, but by perivascular glial cells
(astrocytes) in elasmobranch fish (sharks, skates, and rays). It has
been unclear which is the ancestral form, but this information is
important, as it could offer insights into the roles of the
endothelium and perivascular glia in the modern mammalian BBB. We have
used electron microscopic techniques to examine three further ancient
fish groups, with intravascular horseradish peroxidase as permeability
tracer. We find that in bichir and lungfish the barrier is formed by
brain endothelial cells, while in sturgeon it is formed by a complex
perivascular glial sheath, but with no detectable tight junctions.
From their BBB pattern, and position on the vertebrate family tree, we
conclude that the ancestral vertebrate had a glial BBB. This means
that an endothelial barrier would have arisen independently several
times during evolution, and implies that an endothelial barrier gave
strong selective advantage. The selective advantage may derive partly
from greater separation of function between endothelium and astrocytic
glia. There are important implications for the development,
physiology, and pathology of the mammalian BBB, and for the roles of
endothelium and glia in CNS barrier layers.

Keywords: fish • evolution • brain blood vessels • horseradish
peroxidase • tracer • astrocyte • basal lamina

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Tue, 13 May 2008 13:29:45 -0000

Another publication (with informative Abstract below) that I missed before Malcolm Dean called my attention:

http://jp.physoc.org/cgi/reprint/559/1/3
J Physiol Volume 559(1):3-15, August 15, 2004
DOI: 10.1113/jphysiol.2004.063214
Neurone-to-astrocyte signalling in the brain represents a distinct
multifunctional unit
Tommaso Fellin and Giorgio Carmignoto

Astrocytes can respond to neurotransmitters released at the synapse by
generating elevations in intracellular Ca2+ concentration ([Ca2+]i)
and releasing glutamate that signals back to neurones. This discovery
opens new perspectives for the possible participation of these glial
cells in actual information processing by the brain and raises the
hypothesis that astrocyte activation by neuronal signals plays a key
role in distinct, functional events. Depending on the level of
neuronal activity, the [Ca2+]i response that is activated by
neurotransmitters can either remain restricted to an astrocytic
process or it can propagate as an intracellular [Ca2+]i wave to other
astrocytic processes in contact with different neurones, astrocytes,
microglia or endothelial cells of cerebral arterioles. Glutamate
release triggered by the [Ca2+]i rise at the astrocytic process
represents a feedback, short-distance signal that affects synaptic
transmission locally. The release of glutamate as well as of other
compounds far away from the site of initial activation represents a
feedforward, long-distance signal that can be involved in the
regulation of distinct processes. For instance, through the release of
vasoactive molecules from the astrocytic processes in contact with
cerebral arterioles, the neurone–astrocyte–endothelial cell signalling
pathway plays a pivotal role in the neuronal control of vascular tone.
In this article we will review recent results that should persuade us
to reshape our current thinking on the roles of astroglial cells in
the brain. We propose that neurones and astrocytes represent an
integral unit that has a distinctive role in different fundamental
events in brain function. Furthermore, while recent findings provide
important evidences for the vesicular hypothesis of glutamate release,
we discuss also the proposals for a possible physiological role of
hemichannels and purinergic P2X7 receptors in glutamate release from
astrocytes. A full clarification of the functional significance of the
bidirectional communication that astrocytes establish with neurones as
well as with other brain cells represents one of the most intriguing
challenges in neurobiological research at the moment and should fuel
stimulating debates in years to come.

Reply from Noah Gray

Noah Gray — Fri, 04 Apr 2008 16:23:57 -0000

This is an exciting paper (of course, I’m biased!) Since these cells are technically not fully-differentiated, it will be interesting to see what role the activity plays in causing these cells to become mature oligodendrocytes, or something else…

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Fri, 04 Apr 2008 09:04:30 -0000

Nature Neuroscience 11, 379 – 380 (2008)
doi:10.1038/nn0408-379
Glia get excited

A new study shows that a subset of the glia that express the
proteoglycan NG2 can fire action potentials, contradicting the dogma
that only neurons are excitable in the brain. These glia receive
excitatory and inhibitory synaptic input, are selectively vulnerable
to ischemia and are present into adulthood, though their function
remains mysterious.

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Thu, 29 Nov 2007 11:21:31 -0000

A PubMed search on PG Haydon (one of the leading researchers on astrocytes):

1: J Neurosci. 2007 Jun 13;27(24):6473-7.

Synaptic islands defined by the territory of a single astrocyte.

Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG.

Silvio Conte Center for Integration at the Tripartite Synapse, Department of
Neuroscience, University of Pennsylvania School of Medicine, Philadelphia,
Pennsylvania 19104, USA.

In the mammalian brain, astrocytes modulate neuronal function, in part, by
synchronizing neuronal firing and coordinating synaptic networks. Little,
however, is known about how this is accomplished from a structural standpoint. To
investigate the structural basis of astrocyte-mediated neuronal synchrony and
synaptic coordination, the three-dimensional relationships between cortical
astrocytes and neurons was investigated. Using a transgenic and viral approach to
label astrocytes with enhanced green fluorescent protein, we performed a
three-dimensional reconstruction of astrocytes from tissue sections or live
animals in vivo. We found that cortical astrocytes occupy nonoverlapping
territories similar to those described in the hippocampus. Using
immunofluorescence labeling of neuronal somata, a single astrocyte enwraps on
average four neuronal somata with an upper limit of eight. Single-neuron
dye-fills allowed us to estimate that one astrocyte contacts 300-600 neuronal
dendrites. Together with the recent findings showing that glial Ca2+ signaling is
restricted to individual astrocytes in vivo, and that Ca2+ signaling leads to
gliotransmission, we propose the concept of functional islands of synapses in
which groups of synapses confined within the boundaries of an individual
astrocyte are modulated by the gliotransmitter environment controlled by that
astrocyte. Our description offers a new structurally based conceptual framework
to evaluate functional data involving interactions between neurons and astrocytes
in the mammalian brain.

PMID: 17567808 [PubMed – indexed for MEDLINE]

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Tue, 30 Oct 2007 13:37:04 -0000

Dear All:

Nature Neuroscience (10, 1349, 2007)released a new number focusing on glia. Below I pasted some parts of the Editorial written by Sandra Aamodt.

Best Regards,

Alfredo

“A decade ago, glia were the neglected stepchildren of neuroscience. Although glia outnumber neurons by about ten to 1 in the adult human brain, providing support for neurons has traditionally been viewed as their primary function. Glial biology has come into its own recently, as researchers have shown that glia are critical for the development of the nervous system and have key roles in various neurodegenerative disorders. Glia regulate brain vasculature and the blood-brain barrier, modulating ischemia and migraines. Moreover, they are important in the repair of neurons after injury and also contribute to neuropathology in neurodegenerative diseases. In this issue, we present a focus on glia and disease, which highlights recent efforts in some of these areas and discusses how advances in understanding glial biology may lead to new treatments.
Multiple sclerosis is caused by the malfunction of glia, specifically by the failure of remyelination by oligodendrocytes. ...
Glia are also important in dominantly inherited neurodegenerative diseases, including amyotrophic lateral sclerosis, spinocerebellar ataxia, Parkinson’s disease and Huntington’s disease. ...
Neuropathic pain is triggered by a normally innocuous stimulus or by no stimulus at all. Glia, immune cells and neurons interact to produce neuropathic pain, explain Joachim Scholz and Clifford Woolf in their review. They describe neuropathic pain as a neuroimmune disorder, involving activation of Schwann cells, microglia and astrocytes in a complex temporal and spatial pattern. Blocking the signaling pathways between neurons and non-neuronal cells may offer new ways to prevent or treat this disorder, but a key challenge for the future will be to differentiate the healthy aspects of pathways that are activated in response to pain-inducing stimuli from those that produce neuropathology.
Local control of blood flow in the brain is important for matching neural activity to the brain’s local supply of oxygen and glucose, a process that provides the basis for functional imaging techniques. In their review, Costantino Iadecola and Maiken Nedergaard discuss the mechanisms by which astrocytes regulate microvasculature. Changes in intracellular calcium in astrocytic endfeet regulate vascular tone in the arterioles that they contact. Because synaptic activity is not the only process that influences astrocytic calcium levels and because astrocytes integrate synaptic activity over long time scales, the authors caution that the interpretation of functional brain imaging signals may need to be reevaluated. These results also raise the speculation that astrocytes may participate in cerebrovascular disease.
Astrocytes clearly contribute to one form of cerebrovascular disorder, brain ischemia, which is often caused by stroke. David Rossi, James Brady and Claudia Mohr review the mechanisms by which astrocytes damage and protect neurons that have lost their blood supply. Astrocytic glycogen stores can provide energy to deprived neurons, but can also increase brain damage as a result of lactic acidosis. Release of neurotransmitters such as glutamate from astrocytes can contribute to ischemic brain damage. Because astrocytes are coupled into networks by gap junctions, they are also important in the spread of stroke-induced damage to bystander neurons surrounding the initial injury. Once brain ischemia has begun, it is difficult to deliver drugs to the affected areas, so the authors concentrate on therapeutic agents that could be given to high-risk patients to reduce the damage caused by stroke….”

Reply from Michael Bland

Michael Bland — Tue, 04 Sep 2007 23:15:02 -0000

Hi Alfredo,

When I click on the link, and then click on ‘Full Text’, I read the following: “This item requires a subscription to Proceedings of the National Academy of Sciences Online.” Alternatively, I’m invited to purchase short-term access the article.

Access may be free for you because your university pays for the subscription to National Academy of Sciences, or something like that.

I wouldn’t be inclined to say that autism or schizophrenia are ‘brain illnesses’. Obviously they are, respectively, developmental disorders and mental disorders; they both can be profoundly pathological; and there is no question that understanding the nature of these disorders requires a better understanding of the human nervous system than we currently have.

But equally, they both seem occasionally to be involved in genius.

Moreover, Hans Asperger himself wrote: “The autistic personality is an extreme variant of masculine intelligence, of masculine character.” So if we simply say that autism is a brain illness, then it’s a bit like saying that extreme masculinity is a brain illness. (No doubt some would say that it is indeed.)

Best wishes,
Michael

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Fri, 31 Aug 2007 21:31:40 -0000

Dear Michael:

This publication is free, just click on the link in my first message (“new paper by D. Premack”).

I do not have a good answer for your question.
I will wait for a help from other members of the group.

My suggestion is that the author called “neurodegenerative” to brain illnesses that begin after the first years of life.

Best Regards

Alfredo

Reply from Michael Bland

Michael Bland — Fri, 31 Aug 2007 20:29:28 -0000

Dear Alfredo,

Please could you help me out here:

Everyone knows that the symptoms of Alzheimer’s disease are the result of neurodegeneration.

But that schizophrenia and autism are also neurodegenerative ‘diseases’ – as stated in the above quote – is a new one on me.

Or is it just now accepted that autism and schizophrenia must somehow be neurodegenerative diseases?

I’m afraid I haven’t read the article because I can’t afford to start buying articles online.

With best wishes,
Michael