NT-3 Update (another rodent study)

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Neurotrophin-3 prevents mitochondrial dysfunction in sensory neurons

of streptozotocin-diabetic rats.

(NOTE: We have followed the development of NT-3 research here at

for several years. It still remains that there has only been the one

clinical human trial for CMT. If you are new here, you can go back in the

archives to October 2003 to read about the results of this human trial, or go

even farther back to read about how the trial was conducted. I am posting this

for information even though it is about another rodent study and is about

diabetic neuropathy.

~ Gretchen)

Exp Neurol, July 1, 2005; 194(1): 279-83.

Neurotrophin-3 prevents mitochondrial dysfunction in sensory neurons

of streptozotocin-diabetic rats.

TJ Huang, NM Sayers, A Verkhratsky, and P Fernyhough

School of Biological Sciences, University of Manchester, Manchester,

UK.

Sensory neurons from streptozotocin (STZ)-diabetic rats exhibit

depolarization of mitochondria and the related induction of reactive

oxygen species has been proposed to contribute to the etiology of

sensory polyneuropathy in diabetes. There is deficient neurotrophin-3

(NT-3)-dependent neurotrophic support of sensory neurons in diabetes

and treatment of STZ-diabetic rats with NT-3 prevents

neuropathological alterations in peripheral nerve. Therefore, we

hypothesized that loss of NT-3 may contribute to mitochondrial

dysfunction in sensory neurons in diabetic sensory neuropathy. The

specific aim of this study was to determine whether treatment of STZ-

diabetic rats with systemic NT-3 could prevent depolarization of the

mitochondrial inner membrane potential (Deltapsi(m)). In vitro

studies with cultured DRG neurons from control rats revealed that

treatment with 50 ng/ml NT-3 for 6 h enhanced the Deltapsi(m), e.g.,

a higher polarized membrane potential, compared to untreated neurons

(P < 0.05).

Studies on DRG sensory neurons from control vs. STZ-diabetic rats

demonstrated that NT-3 therapy prevented the diabetes-induced

depolarization of Deltapsi(m) (P < 0.05) in parallel with

normalization of diabetes-dependent deficits in sensory nerve

conduction velocity. Furthermore, alterations in mitochondrial

function in vitro and in vivo correlated with the level of

activation/expression of Akt in DRG neurons.