Neurobiology basis for Schizophrenia finally uncovered?

[James Zheng]

Schizophrenia (精神分裂症) is a mental disease compromised by a devastating
array of psychotic, emotional and cognitive symptoms. For those of
you who do not know much about Schizophrenia, go to Blockbuster video
and rent the movie "A beautiful mind". While psychiatric diagnosis
and limited treatments are available, the biological basis for
Schizophrenia is virtually unknown, up until now. While
Schizophrenia has been thought to be a brain disease, neuroscience
research on Schizophrenia has been very slow in making progress (You
can not blame this on scientists - We use mice and rats to study brain
functions and disorders and how can we tell is a mouse or rat is
schizophrenic - Schizophrenia is thought to be a human-unique
disorder). In the May issue of NEURON, two papers provide evidence
that link neuregulin-ErbB signaling in synaptic activity in to
Schizophrenia. For a brief summary of these findings, please read the
news & view on Nature by Lorna Role and David A. Talmage (the pdf file
is provided in this group).

1. Li, B., Woo, R.-S., Mei, L. & Malinow, R. The Neuregulin-1 Receptor
ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity.
Neuron 54, 583–597(2007).
2. Woo, R.-S. et al. Neuregulin-1 Enhances Depolarization-Induced GABA
Release. Neuron 54, 599–610 (2007).

[neuroscience]

Schizophrenia is likely also associated with dopamine D2 receptors.
Is there any link between D2 and NGR1? Or they go through different
pathways (dopamine vs glutamate pathway)?

[Dani]

Although there is a "glutamate" pathway in the brain (but no one
really calls it that), if you read about where it is you would soon
realize that it encompasses the entire brain.....from cortico-cortical
pathways, cortico-thalamic, and cortico-substantia nigra/globus
pallidus etc etc. That is basically most major pathways INCLUDING the
Dopaminergic system and considering glutamate is the major excitatory
NT in the brain and glutamate receptors are found on almost every CNS
neuron many (dopamine neurons will also contain GluRs. This means that
if NRG1 (short for NeuReGulin-1, not NGR1) has now been shown to be
important for GluR functioning then chances are it may play a role in
dopaminergic neurons somewhere. Its a good thought though.

[Dani]

These are elegant papers that deserves to be in Neuron....now if only
we could get some of their cool toys. My only concern is the claim
that this may provide a strong link for an etiology of Schizophrenia.
As I just wrote in my previous post, GluRs are basically everywhere in
the brain and therefore their hypoactivity leading to some sort of
mental disorder is not exactly discovering fire. Glutamate/GluR
dysfunction have already been associated with Autism, fragile X,
William's Syndrome not to mention a host of other mental disorders so
it would not be surprising if it were also implicated in
Schizophrenia. I guess it puts a more modern twist on the DA
hypothesis of the disease, but I don't think at this point much more
can be said. These papers are important because of the work done to
elucidate the cellular roles that NRG1 and erbB4 play at the post-
synaptic level, but thats about it.