Hi Dr. Phelps,
Just saw this on the CABF message board....Thought you might like to read it
Thank YOu for your great work great work!!
Medications and other Treatments for BP
From: Martha (CABF)
Subject: Mitochondria (from Husseini Manji, M.D.)
Date: 1/7/2003 11:17:12 AM
Message Board | Post New Topic
Mitochondria are organelles (within a cell) that generate the major molecule
(ATP) by which cellular energy is transferred or spent. Think of them as the
(rechargeable) batteries of the cell. ATP is used to "power" everything that the
cell does--of interest to us, it is essential in the making of
neurotransmitters, and also contributes to muscle tone.
Dr. Husseini Manji, Chief of the Laboratory of Molecular Pathophysiology at the
NIMH, who is working on bipolar disorder, writes to us this morning:
"...just like not being a "classical" neurodegenerative disease, bipolar does
not have many of the features of classic mitochondrial diseases, but I think
that its quite plausible that we have an impairment of mitochondrial function.
"Its an area *very dear* to my heart (that's what bcl-2 [a neuroprotective
protein enhanced by lithium and some other treatments that promotes cellular
survival and protects the mitochondria, in particular, from apoptosis] mainly
does for a living --regulate mitochondrial function), and it's undoubtedly
involved in *treatment* and potentially at least in subgroups of bipolars. It's
something we are investigating extensively in our animal/cell studies, and
getting geared up to do extensive human studies (where we would
simultaneously look at peripheral (blood cell or skin) mitochondrial
function directly, and at the same time do brain imaging (MRS measures of
lactate might be an indirect "readout" of the neurons' ability to handle
loads/demands). This is one area where I think at least some bipolars
differ from unipolars -- I think that bipolars may have an inherent
impairment of what I call cellular resilience, and therefore even normal
loads are excessive and exact a toll on the brain (is this why we see
white matter hyperintensities in many young bipolars? (something "normally"
associated with aging/cerebrovascular disease?))... *very recent* evidence
suggests that mitochondria in nerve terminals also play an important role in
regulating neurotransmitter release, and so abnormalities could be
associated not only with cell loss/atrophy/white matter hyperintensities, but
also "moment to moment" neurotransmitter release.
[Is this related to] mitochondrial *genes* (these are inherited only from
the mother) in bipolar disorder? -- I think that the current evidence is weak.
However, I think that its pretty likely that we will find abnormal mitochondrial
*function* in bipolars (as I mentioned, maybe a subset) -- could be due to
abnormalities at any step in neurotrophic cascades which regulate bcl-2, some of
its partners, the mitochondrial "pore", etc (doesn't need to be mitochondrial
genes themselves). These abnormalities would also explain the many, many
findings of calcium abnormalities in blood cells in bipolars.
So its a *very important* area, and something we are pursuing preclinically and
hopefully clinically soon.
Dear Ms. B' --
Thanks very much for passing that along. Isn't it a great thing that
somebody like Dr. Manji is taking the time to write to a "patients (and
families)" bulletin board?! I copied his letter into the section of
my website on his work, as his personal expansion of those themes; and wrote to
thank him. So thank you for making that happen.
Published January, 2003