Progesterone and its derivatives are neuroprotective agents in experimental diab

[Guest guest]

(NOTE: I realize this is about diabetic neuropathy, but sometimes

peripheral neuropathy treatments start here. Progesterone and its

derivatives were first discovered in Germany (remember Onapristone?)

so this looks like some 'progress' for PN research in general, and

then hopefully for CMT. ~ Gretchen)

Neuroscience. 2006 Dec 19

Progesterone and its derivatives are neuroprotective agents in

experimental diabetic neuropathy: A multimodal analysis.

Leonelli E, Bianchi R, Cavaletti G, Caruso D, Crippa D, -

Segura LM, Lauria G, Magnaghi V, Roglio I, Melcangi RC.

Department of Endocrinology and Center of Excellence on

Neurodegenerative Diseases, University of Milan, Via Balzaretti 9,

20133 Milano, Italy.

One important complication of diabetes is damage to the peripheral

nervous system. However, in spite of the number of studies on human

and experimental diabetic neuropathy, the current therapeutic

arsenal is meager. Consequently, the search for substances to

protect the nervous system from the degenerative effects of diabetes

has high priority in biomedical research.

Neuroactive steroids might be interesting since they have been

recently identified as promising neuroprotective agents in several

models of neurodegeneration. We have assessed whether chronic

treatment with progesterone (P), dihydroprogesterone (DHP) or

tetrahydroprogesterone (THP) had neuroprotective effects against

streptozotocin (STZ)-induced diabetic neuropathy at the

neurophysiological, functional, biochemical and neuropathological

levels.

Using gas chromatography coupled to mass-spectrometry, we found that

three months of diabetes markedly lowered P plasma levels in male

rats, and chronic treatment with P restored them, with protective

effects on peripheral nerves. In the model of STZ-induced of

diabetic neuropathy, chronic treatment for 1 month with P, or with

its derivatives, DHP and THP, counteracted the impairment of nerve

conduction velocity (NCV) and thermal threshold, restored skin

innervation density, and improved Na(+),K(+)-ATPase activity and

mRNA levels of myelin proteins, such as glycoprotein zero and

peripheral myelin protein 22, suggesting that these neuroactive

steroids, might be useful protective agents in diabetic neuropathy.

Interestingly, different receptors seem to be involved in these

effects.

Thus, while the expression of myelin proteins and Na(+),K(+)-ATPase

activity are only stimulated by P and DHP (i.e. two neuroactive

steroids interacting with P receptor, PR), NCV, thermal nociceptive

threshold and intra-epidermal nerve fiber (IENF) density are also

affected by THP, which interacts with GABA-A receptor.

Because, a therapeutic approach with specific synthetic receptor

ligands could avoid the typical side effects of steroids, future

experiments will be devoted to evaluating the role of PR and GABA-A

receptor in these protective effects.