TY - JOUR
T1 - Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy
AU - Roglio, I.
AU - Bianchi, R.
AU - Giatti, S.
AU - Cavaletti, G.
AU - Caruso, D.
AU - Scurati, S.
AU - Crippa, D.
AU - Garcia-Segura, L. M.
AU - Camozzi, F.
AU - Lauria, G.
AU - Melcangi, R. C.
PY - 2007/5
Y1 - 2007/5
N2 - In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5αandrostan-3α, 17β-diol (3α-diol) therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted in decreased T and increased 3α-diol levels in plasma and in decreased levels of pregnenolone and DHT in the sciatic nerve. Moreover, a reduced expression of the enzyme converting Tinto DHT (i.e., the 5α-reductase) also occurs at the level of sciatic nerve, suggesting that the decrease of DHT levels could be due to an impairment of this enzyme. Chronic treatment for 1 month with DHT or 3α-diol increased tail nerve conduction velocity and partially counteracted the increase of thermal threshold induced by diabetes. Treatment with DHT increased tibial Na+,K+-ATPase activity and the expression of myelin protein P0 in the sciatic nerve.DHT, 3α-diol and T reversed the reduction of intra-epidermal nerve fiber density induced by diabetes. These observations indicate that T metabolites can reverse behavioral, neurophysiological, morphological and biochemical alterations induced by peripheral diabetic neuropathy.
AB - In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5αandrostan-3α, 17β-diol (3α-diol) therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted in decreased T and increased 3α-diol levels in plasma and in decreased levels of pregnenolone and DHT in the sciatic nerve. Moreover, a reduced expression of the enzyme converting Tinto DHT (i.e., the 5α-reductase) also occurs at the level of sciatic nerve, suggesting that the decrease of DHT levels could be due to an impairment of this enzyme. Chronic treatment for 1 month with DHT or 3α-diol increased tail nerve conduction velocity and partially counteracted the increase of thermal threshold induced by diabetes. Treatment with DHT increased tibial Na+,K+-ATPase activity and the expression of myelin protein P0 in the sciatic nerve.DHT, 3α-diol and T reversed the reduction of intra-epidermal nerve fiber density induced by diabetes. These observations indicate that T metabolites can reverse behavioral, neurophysiological, morphological and biochemical alterations induced by peripheral diabetic neuropathy.
KW - 3α-diol
KW - 5α-reductase
KW - Androgen receptor
KW - Dihydrotestosterone
KW - Neuroactive steroids
KW - Rat
KW - Sciatic nerve
KW - Streptozotocin
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U2 - 10.1007/s00018-007-7002-5
DO - 10.1007/s00018-007-7002-5
M3 - Article
C2 - 17417742
AN - SCOPUS:34247584094
VL - 64
SP - 1158
EP - 1168
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 9
ER -