TY - JOUR
T1 - Sex differences in the manifestation of peripheral diabetic neuropathy in gonadectomized rats
T2 - A correlation with the levels of neuroactive steroids in the sciatic nerve
AU - Pesaresi, Marzia
AU - Giatti, Silvia
AU - Cavaletti, Guido
AU - Abbiati, Federico
AU - Calabrese, Donato
AU - Bianchi, Roberto
AU - Caruso, Donatella
AU - Garcia-Segura, Luis Miguel
AU - Melcangi, Roberto C.
PY - 2011/4
Y1 - 2011/4
N2 - Clinical observations suggest a sex-dimorphism in the incidence and symptomatology of diabetic neuropathy, but this possible gender effect has never been investigated in detail in a well-characterized experimental model such as streptozotocin (STZ)-induced diabetes. Therefore, in this study we have compared with a multimodal set of tests the impact of diabetes on the sciatic nerve in male and female rats. To assess whether sex-dimorphism in peripheral diabetic neuropathy is dependent on gonadal hormones we have also analyzed the effect of ovariectomy and orchidectomy on the sciatic nerve of STZ-diabetic rats. Nerve conduction velocity (NCV), Na+,K+-ATPase activity, expression of myelin proteins, thermal sensitivity and reactive oxygen species production were similarly affected in male and female animals by STZ. However, ovariectomy, but not orchidectomy, significantly counteracted STZ-induced alterations on NCV, Na+,K+-ATPase activity, and expression of myelin proteins. This effect of ovariactomy was associated to an increase in the levels of neuroactive steroids, such as dehydroepiandrosterone, testosterone and dihydrotestosterone, in the sciatic nerve of diabetic rats. These neuroactive steroids have been demonstrated to be protective agents in this experimental model of diabetic neuropathy. However, their efficacy has been so far tested only in male animals. Therefore, the present data might represent an important background to evaluate their efficacy also in female diabetic animals.
AB - Clinical observations suggest a sex-dimorphism in the incidence and symptomatology of diabetic neuropathy, but this possible gender effect has never been investigated in detail in a well-characterized experimental model such as streptozotocin (STZ)-induced diabetes. Therefore, in this study we have compared with a multimodal set of tests the impact of diabetes on the sciatic nerve in male and female rats. To assess whether sex-dimorphism in peripheral diabetic neuropathy is dependent on gonadal hormones we have also analyzed the effect of ovariectomy and orchidectomy on the sciatic nerve of STZ-diabetic rats. Nerve conduction velocity (NCV), Na+,K+-ATPase activity, expression of myelin proteins, thermal sensitivity and reactive oxygen species production were similarly affected in male and female animals by STZ. However, ovariectomy, but not orchidectomy, significantly counteracted STZ-induced alterations on NCV, Na+,K+-ATPase activity, and expression of myelin proteins. This effect of ovariactomy was associated to an increase in the levels of neuroactive steroids, such as dehydroepiandrosterone, testosterone and dihydrotestosterone, in the sciatic nerve of diabetic rats. These neuroactive steroids have been demonstrated to be protective agents in this experimental model of diabetic neuropathy. However, their efficacy has been so far tested only in male animals. Therefore, the present data might represent an important background to evaluate their efficacy also in female diabetic animals.
KW - Dehydroepiandrosterone
KW - Diabetes
KW - Dihydrotestosterone
KW - Liquid chromatography-tandem mass spectrometry
KW - Neuroprotection
KW - Neurosteroids
KW - Peripheral nervous system
KW - Streptozotocin
KW - Testosterone
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U2 - 10.1016/j.expneurol.2011.01.005
DO - 10.1016/j.expneurol.2011.01.005
M3 - Article
C2 - 21241692
AN - SCOPUS:79952690529
VL - 228
SP - 215
EP - 221
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 2
ER -