Astrocytes, the cells
that make the background of the brain and support neurons, might be behind mental
disorders such as depression and schizophrenia, according to new research by a
Portuguese team from the ICVS at the University of Minho.  The study, in this month Molecular Psychiatry, shows how a simple reduction of astrocytes in
the prefrontal cortex (which is linked to cognition) can kill its neurons and
lead to the cognitive deficits that characterise several mental diseases. Although
malfunctioning astrocytes have been found in psychiatric patients before, it was unclear if they were a cause or consequence of the disease.

“This is the first time that cognitive deficits of a
psychiatric illness can be mimicked by solely affecting astrocytes” - says the
team leader, João Filipe Oliveira – “opening a whole new range of possibilities,
both on the causes and potential treatments for these disorders.“  

The research by Ana Raquel Lima, João Filipe Oliveira and colleagues is particularly significant
when we look at the heavy burden in human suffering and financial cost
of mental diseases. Just in the US and Europe about 1 in 4 adults are affected in
every given year (an incredible 26% of their population), while depression alone
uses almost 5% of the total world health budget. And after all, a new player behind a
disease is a door to new and, maybe, more effective treatments.

So what are astrocytes? These star-shaped cells are part of
the so called “glial population” - non-neuron cells that form the brain
background and that for a long time were considered mere  “housekeepers” of the real players - the
neurons. In fact, traditionally, brain
function is the result of electrical impulses passing between neurons,
transmitting the information necessary for all those extraordinary abilities of
this brains ours, from memory storage and motor control to personality quirks.

But astrocytes, even when believed to be “the help”, have already
been the subject of much curiosity since it was claimed by some (and denied by
others) that one of the few uniqueness of Einstein’s brain was larger and more
complex astrocytes 

Images from silent film sdepicting institutionalized patients, and text  defining schizophrenia and some of the symptoms associated with the disorder. Courtesy of the National Library of Medicine. Images from the History of Medicine (IHM), http://ihm.nlm.nih.gov/images/A109142 

within its cerebral cortex than “normal” individuals. Equally
curious, was the fact that these are the
most numerous cells in the mammalian brain, because keeping cells alive costs energy,
which is always in short supply, and astrocytes were not even part of the of main
action/brain activity. Or so it was thought.

In fact, the last decade has seen our ideas on astrocytes
(and glial cells in general) change radically; we now known they perform highly
complex jobs, including several previously associated with neurons. They are,
for example, important for synapses (the
specialised structures that do the contact between different neurons and through
which the electrical signal is transmitted), where astrocytes detect and modulate
activity, so effectively controlling the transmission of information in the
brain.

Supporting their importance in the brain, several studies have
shown that patients with mental diseases - such as depression, bipolar disorder
and schizophrenia – have lower than normal astrocyte density in the brain, especially
in the prefrontal cortex. This can be improved, though, with anti-psychotic
drugs.

This not only supports the importance of astrocytes in
normal brain function, but also suggests they could play a role in mental
disorders. And in fact, in one study killing astrocytes in the prefrontal
cortex of rats seemed to cause a depression-like behaviour. But even if faulty
astrocytes and mental diseases were often seen together, it was not possible to
be sure, at least in psychiatric patients, that these cells were behind the disorder.

It is in this state of affairs that Lima and colleagues, in
the work now published, decided to design a simple but very effective experiment
to understand what was happening.

They start by injecting rats in the prefrontal cortex with a
toxin that specifically kills astrocytes in a very localized way, and then tested
the animals’ cognitive abilities correlating these with the animals’ (changed?)
brain structure. The prefrontal cortex was chosen because it controls cognitive
abilities such as planning, reasoning and problem solving, which are affected not only in the
most common mental diseases, but also on age-related neurodegenerative
illnesses like Alzheimer’s.

As expected toxin-injected animals developed the cognitive deficits
typical of mental disorders where the prefrontal cortex is affected. But what was
really interesting, were the brain changes found - not only the prefrontal
cortex’s astrocytes had died with the toxin (as expected) but, as time passed,
also did its neurons. Control animals injected with a solution free of toxin had
no changes, either in behaviour or brain structure.

So even if faulty astrocytes have been found before in mental
patients, the Portuguese researchers’ results give robust support to the idea
that astrocyte breakdown can be a primordial cause for these disorders (and not
a result of them), and also suggests how it occurs 

 “Until now, we have blamed the poorer performance of the prefrontal
cortex in these diseases on the surrounding astrocyte pathology” - says Oliveira
– “but this study now supports the view that astrocytes, targeted in a
pathological process, may actually lead to neurodegeneration in a specific
brain region. Psychiatric disease can be mimicked by simply affecting
astrocytes!”

This is a totally new perspective on how these diseases can develop,
and consequently on how to treat them. For now, while we do not test other
brain areas, Oliveira’s results are specially relevant for mood disorders
diseases - depression, schizophrenia and bipolarity - which we know to have both
loss of cognitive functions, and abnormalities in the astrocytes of the prefrontal
cortex.  

But Oliveira and his team’s findings are also important challenging the still too present view of
the brain as a simple network of neurons, clearly showing that we need to see
it instead as an interdependent circuit of neural and glial cells (in
particular astrocytes) both in health and disease.

The new work also makes us also wonder if the claims on
the importance of the astrocytes in Einstein’s brain were that crazy after all…