Neuroprotective effects of a ligand of translocator protein-18kDa (Ro5-4864) in experimental diabetic neuropathy

Giatti, Silvia; Pesaresi, Marzia; Cavaletti, Guido; Bianchi, Roberto; Carozzi, Valentina Alda; Lombardi, Raffaella; Maschi, Omar; Lauria, Giuseppe; García‐Segura, Luis M.; Caruso, Donatella; Melcangi, Roberto Cosimo

doi:10.1016/j.neuroscience.2009.08.005

Cited by 83 publications

(68 citation statements)

References 56 publications

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“…The consequences of the regulation of Tspo by 3a-diol are unknown. However, previous observations of STZ-rats have demonstrated that the activation of Tspo by a synthetic ligand such as Ro5-4864, exerts neuroprotective effects on peripheral nerves (Giatti et al 2009), and increases the levels of neuroactive steroids, such as DHT, in the peripheral nerves and the spinal cord (Mitro et al 2012).…”

Section: Discussionmentioning

confidence: 93%

“…A role for TSPO in diabetes (Giatti et al 2009) and neuropathic pain (Wei et al 2013) has been proposed, suggesting that neuroactive steroids may participate in the control of neuropathic pain. Indeed, some neuroactive steroids exert antinociceptive actions in different animal models (Goodchild et al 2000, Winter et al 2003, Todorovic et al 2004, Mensah-Nyagan et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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Diabetic neuropathic pain: a role for testosterone metabolites

Calabrese¹,

Giatti²,

Romano³

et al. 2014

Journal of Endocrinology

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Diabetic neuropathy is associated with neuropathic pain in about 50% of diabetic subjects. Clinical management of neuropathic pain is complex and so far unsatisfactory. In this study, we analyzed the effects of the testosterone metabolites, dihydrotestosterone (DHT), and 3a-diol, on nociceptive and allodynia thresholds and on molecular and functional parameters related to pain modulation in the dorsal horns of the spinal cord and in the dorsal root ganglia of rats rendered diabetic by streptozotocin injection. Furthermore, the levels of DHT and 3a-diol were analyzed in the spinal cord. Diabetes resulted in a significant decrease in DHT levels in the spinal cord that was reverted by DHT or 3a-diol treatments. In addition, 3a-diol treatment resulted in a significant increase in 3a-diol in the spinal cord compared with control values. Both steroids showed analgesic properties on diabetic neuropathic pain, affecting different pain parameters and possibly by different mechanisms of action. Indeed, DHT counteracted the effect of diabetes on the mechanical nociceptive threshold, pre-and post-synaptic components, glutamate release, astrocyte immunoreactivity, and expression of interleukin-1b (IL1b), while 3a-diol was effective on tactile allodynia threshold, glutamate release, astrocyte immunoreactivity and the expression of substance P, toll-like receptor 4, tumor necrosis factor-a, transforming growth factor b-1, IL1b, and translocator protein. These results indicate that testosterone metabolites are potential agents for the treatment of diabetic neuropathic pain.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Diabetic neuropathic pain: a role for testosterone metabolites

Calabrese¹,

Giatti²,

Romano³

et al. 2014

Journal of Endocrinology

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“…[16][17][18] In experimental models of diabetic neuropathy, neuroactive steroids have been shown to be neuroprotective. [17][18][19] A previous study from this laboratory has revealed that koumine could increase allopregnanolone, a type of neuroactive steroids, in the spinal cord of CCI rats, 4) raising the possibility that koumine alleviates diabetes-induced neuropathic pain by increasing neuroactive steroids in the peripheral nervous system.…”

Section: Discussionmentioning

confidence: 99%

Anti-allodynic and Neuroprotective Effects of Koumine, a Benth Alkaloid, in a Rat Model of Diabetic Neuropathy

Ling

Liu

et al. 2014

Biological & Pharmaceutical Bulletin

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Diabetic neuropathy is characterized by progressive degeneration of nerve fibers associated with diabetes mellitus. Antidepressants and anticonvulsants are the mainstay of pharmacological treatment, but are often limited in effectiveness against the core clinical feature of pain. In the current study, we examined the potential effects of koumine, a Gelsemium elegans BENTH alkaloid, using a rat model of diabetic neuropathy. Rats were administered intraperitoneally a single dose of streptozocin (60 mg/kg) to induce type 1 diabetes. Koumine was given at a dose range of 0.056-7 mg/kg subcutaneously for one week starting 3 weeks after streptozocin adminstration. Behavioral responses to mechanical stimuli were evaluated every day after streptozocin injection. At 4 weeks after streptozocin injection, sensory nerve conduction velocity (SNCV) and morphological alternation of sciatic nerves were assessed by electron microscopy. Diabetic rats developed mechanical hyperalgesia within 3 weeks after streptozocin injection and exhibited reduced SNCV and impaired myelin/axonal structure. Koumine treatment of diabetic rats decreased neuropathic pain behavior as early as after the first administration. At a dose of 7 mg/kg, koumine was more effective than gabapentin (100 mg/kg), and decreased mechanical sensitivity threshold to a level comparable to healthy control. Repeated treatment of koumine significantly reduced the damage to axon and myelin sheath of the sciatic nerve and increased SNCV, without affecting body weight and blood glucose. These findings encourage the use of koumine in the treatment of diabetic neuropathy.

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“…The activation of LXRs, inducing genes involved in cholesterol efflux, like the ATP binding cassette family of transporters (i.e., ABCA1, ABCG1), promotes cholesterol utilization [138]. Recently, we have applied with success these two strategies in an experimental model of diabetes, observing that ligands of TSPO or LXRs are able to increase neuroactive steroid levels directly in the central [139] as well as in peripheral nervous system [140,141]. In particular, the effect of the ligand of LXRs was particularly interesting, because at variance to that of TSPO, did not induce significant changes of neuroactive steroid levels in plasma [139].…”

Section: May the Plasma Levels Of Neuroactive Steroids Be Considered mentioning

confidence: 99%