Etifoxine improves peripheral nerve regeneration and functional recovery
Christelle Girard,Song Liu,Françoise Cadepond,David H. Adams,Catherine Lacroix,Marc Verleye,Jean-Marie Gillardin,Etienne-Emile Baulieu,Michael Schumacher,Ghislaine Schweizer-Groyer +9 more
TLDR
This work demonstrates that etifoxine, a clinically approved drug already used for the treatment of anxiety disorders, is remarkably efficient in promoting acceleration of peripheral nerve regeneration and functional recovery.Abstract:
Peripheral nerves show spontaneous regenerative responses, but recovery after injury or peripheral neuropathies (toxic, diabetic, or chronic inflammatory demyelinating polyneuropathy syndromes) is slow and often incomplete, and at present no efficient treatment is available. Using well-defined peripheral nerve lesion paradigms, we assessed the therapeutic usefulness of etifoxine, recently identified as a ligand of the translocator protein (18 kDa) (TSPO), to promote axonal regeneration, modulate inflammatory responses, and improve functional recovery. We found by histologic analysis that etifoxine therapy promoted the regeneration of axons in and downstream of the lesion after freeze injury and increased axonal growth into a silicone guide tube by a factor of 2 after nerve transection. Etifoxine also stimulated neurite outgrowth in PC12 cells, and the effect was even stronger than for specific TSPO ligands. Etifoxine treatment caused a marked reduction in the number of macrophages after cryolesion within the nerve stumps, which was rapid in the proximal and delayed in the distal nerve stumps. Functional tests revealed accelerated and improved recovery of locomotion, motor coordination, and sensory functions in response to etifoxine. This work demonstrates that etifoxine, a clinically approved drug already used for the treatment of anxiety disorders, is remarkably efficient in promoting acceleration of peripheral nerve regeneration and functional recovery. Its possible mechanism of action is discussed, with reference to the neurosteroid concept. This molecule, which easily enters nerve tissues and regulates multiple functions in a concerted manner, offers promise for the treatment of peripheral nerve injuries and axonal neuropathies.read more
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Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders
Rainer Rupprecht,Vassilios Papadopoulos,Gerhard Rammes,Thomas C. Baghai,Jinjiang Fan,Nagaraju Akula,Ghislaine Groyer,David H. Adams,Michael Schumacher +8 more
TL;DR: The translocator protein (18 kDa) (TSPO) is localized primarily in the outer mitochondrial membrane of steroid-synthesizing cells, including those in the central and peripheral nervous system, which is a prerequisite for steroid synthesis.
Journal ArticleDOI
Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis.
Kanako Morohaku,Susanne H. Pelton,Daniel J. Daugherty,W. Ronald Butler,Wenbin Deng,Vimal Selvaraj +5 more
TL;DR: The results show that TSPO function is not essential for steroid hormone biosynthesis and challenge the prevailing dogma that claims an essential role for T SPO in steroid hormone synthesis and force reexamination of functional interpretations made for this protein.
Journal ArticleDOI
Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system
Katharina Zimmermann,Jochen K. Lennerz,Alexander Hein,Andrea S. Link,J. Stefan Kaczmarek,Markus Delling,Serdar Uysal,John D. Pfeifer,Antonio Riccio,David E. Clapham +9 more
TL;DR: It is found that TRPC5 is present in mouse and human sensory neurons of dorsal root ganglia, a substantial number of peripheral nerves including intraepithelial endings, and in the dorsal lamina of the spinal cord that receives sensory input from the skin, consistent with a potentialTRPC5 function as an innocuous cold transducer in nociceptive and thermosensory nerve endings.
Journal ArticleDOI
CuCl/DABCO/4-HO-TEMPO-Catalyzed Aerobic Oxidative Synthesis of 2-Substituted Quinazolines and 4H-3,1-Benzoxazines
TL;DR: The Cu/N-ligand/TEMPO catalytic system was first applied to the aerobic oxidative synthesis of heterocycles and 2-substituted quinazolines and 4H-3,1-benzoxazines were synthesized efficiently from the one-pot reaction of aldehydes with 2-aminobenzylamines and 2 -aminobenzyl alcohols.
Journal ArticleDOI
Macroglia-Microglia Interactions via TSPO Signaling Regulates Microglial Activation in the Mouse Retina
TL;DR: The inducibility and effects of DBI-TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence.
References
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Journal ArticleDOI
Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function.
Vassilios Papadopoulos,Mario Baraldi,Tomás R. Guilarte,Thomas B. Knudsen,Jean Jacques Lacapère,Peter Lindemann,Michael D. Norenberg,David J. Nutt,Abraham Weizman,Ming Rong Zhang,Moshe Gavish +10 more
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Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation
Susan Y. Fu,Tessa Gordon +1 more
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Progesterone synthesis and myelin formation by Schwann cells
H. Koenig,Michael Schumacher,Badia Ferzaz,Anh N. Do Thi,Annie Ressouches,Rachida Guennoun,Ingrid Jung-Testas,Paul Robel,Yvette Akwa,Etienne-Emile Baulieu,Etienne-Emile Baulieu +10 more
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