Role of thyroid hormones and their receptors in peripheral nerve regeneration

Barakat‐Walter, Ibtissam

doi:10.1002/(sici)1097-4695(19990915)40:4<541::aid-neu10>3.0.co;2-q

Cited by 44 publications

(30 citation statements)

References 109 publications

(125 reference statements)

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“…However, direct use of trophic factors in clinical practice is extremely challenging as they are difficult to administer and have severe side effects (8). However, molecules that easily diffuse into nerve tissues, including ligands of the progesterone and thyroid hormone receptors, and immunophilins, have beneficial effects on peripheral nerves in various experimental lesion and disease models (9)(10)(11)(12). We hypothesize that clinically established drugs may be suitable to elevate trophic factor levels to improve the outcome of peripheral nerve injuries.…”

Section: Introductionmentioning

confidence: 99%

Etifoxine promotes glial-derived neurotrophic factor-induced neurite outgrowth in PC12 cells

Zhou

et al. 2013

Molecular Medicine Reports

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Abstract. Nerve regeneration and functional recovery are major issues following nerve tissue damage. Etifoxine is currently under investigation as a therapeutic strategy for promoting neuroprotection, accelerating axonal regeneration and modulating inflammation. In the present study, a well-defined PC12 cell model was used to explore the underlying mechanism of etifoxine-stimulated neurite outgrowth. Etifoxine was found to promote glial-derived growth factor (GDNF)-induced neurite outgrowth in PC12 cells. Average axon length increased from 50.29±9.73 to 22.46±5.62 µm with the use of etifoxine. However, blockage of GDNF downstream signaling was found to lead to the loss of this phenomenon. The average axon length of the etifoxine group reduces to a normal level after the blockage of the GDNF family receptor α1 (GFRα1) and receptor tyrosine kinase (RETS) receptors (27.46 ± 3.59 vs. 22.46 ± 5.62 µm and 25.31±3.68 µm vs. 22.46±5.62 µm, respectively, p>0.05). In addition, etifoxine markedly increased GDNF mRNA and protein expression (1.55-and 1.36-fold, respectively). However, blockage was not found to downregulate GDNF expression. The results of the current study demonstrated that etifoxine stimulated neurite outgrowth via GDNF, indicating that GDNF represents a key molecule in etifoxine-stimulated neurite outgrowth in PC12 cells. IntroductionTraumatic injury to peripheral nerves results in considerable loss of sensory and motor function, decreasing quality of life in patients (1). Peripheral nerve injuries substantially impact quality of life through loss of function and increased risk of secondary disabilities from falls, fractures and other injuries. Several research groups have attempted to improve the regeneration of traumatized nerves by developing favorable microsurgical techniques. However, clinicians soon noted that despite advancement in these techniques, complete recovery is rarely achieved (2,3). Therefore, complete recovery remains an important clinical challenge for the improvement of functional recovery following peripheral nerve injury. In a discussion of future trends in the management of brachial plexus injuries, Birch hypothesized that the administration of nerve growth factor may represent a useful treatment strategy (4).Neurotrophic factors are important in a number of biological processes, including survival, proliferation, differentiation and apoptosis of neurons in the nervous system (5-7). However, direct use of trophic factors in clinical practice is extremely challenging as they are difficult to administer and have severe side effects (8). However, molecules that easily diffuse into nerve tissues, including ligands of the progesterone and thyroid hormone receptors, and immunophilins, have beneficial effects on peripheral nerves in various experimental lesion and disease models (9-12). We hypothesize that clinically established drugs may be suitable to elevate trophic factor levels to improve the outcome of peripheral nerve injuries.Previous studies have demonstrated that the drug, etifoxi...

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Section: Introductionmentioning

confidence: 99%

Etifoxine promotes glial-derived neurotrophic factor-induced neurite outgrowth in PC12 cells

Zhou

et al. 2013

Molecular Medicine Reports

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“…However, some reports have suggested that thyroid hormones contribute to the reduction of neurologic deficits after injury. For example, thyroid hormones seem to be essential for peripheral nerve repair by acceleration of axonal regeneration and neuromuscular reinnervation (for a review, see Barakat-Walter, 1999). Thyroid hormones would also promote axonal growth in the spinal cord and brain of adult animals (Harvey and Srebnik, 1967;Fertig et al, 1971;Guth, 1974;Heinicke, 1977).…”

Section: Introductionmentioning

confidence: 99%

Induction of Type 2 Iodothyronine Deiodinase in Astrocytes after Transient Focal Cerebral Ischemia in the Rat

Margaill

Royer

Lerouet

et al. 2005

J Cereb Blood Flow Metab

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This study investigated the expression of deiodinases of thyroid hormones in the rat brain after transient occlusion of the middle cerebral artery. The activity of type 2 deiodinase (D2), which catalyzes the deiodination of thyroxine into the more active thyroid hormone 3,5,3 0 -triiodothyronine, was strongly increased by cerebral ischemia at 6 and 24 hours in the striatum and at 24 hours in the cerebral cortex. The activity of type 3 deiodinase, which catalyzes the inactivation of thyroid hormones, was not affected by ischemia. In situ hybridization showed, as soon as 6 hours, an upregulation of the expression of D2 mRNA in the ipsilateral striatum, which disappeared at 24 hours. In the ipsilateral cortex, the induction of D2 mRNA started at 6 hours, was increased at 24 hours and finally declined at 72 hours. These results were confirmed by reverse transcription-PCR for D2 mRNA in the striatum and cerebral cortex. The upregulation of D2 mRNA after ischemia was mainly localized in astrocytic cell bodies. These results show that D2 is rapidly induced in astrocytes after ischemic stroke. Future work will include the exploration of the role of the upregulation of this enzyme, responsible for local 3,5,3 0 -triiodothyronine production as a neuroprotective mechanism in the brain.

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“…Since our interest is focused on the study of the effect of a local administration of T 3 on the regeneration of transected adult rat sciatic nerve (Voinesco et al, 1998;Barakat-Walter, 1999;Schenker et al, 2002), we used the physical disector method to estimate the total number of surviving neurons in lumbar DRG in control and experimental animals. To this aim we analysed a large number of disector pairs separated by 50 m and we found that the mean number of neurons in PBS-control is 8744 ± 748 and the mean number of neurons in T 3 -treated ganglion is 12046 ± 930 (Schenker et al, 2003).…”

Section: Physical Disector and Direct Counting Methods Confirmed Thatmentioning

confidence: 99%

Does the physical disector method provide an accurate estimation of sensory neuron number in rat dorsal root ganglia?

Delaloye¹,

Kraftsik²,

Küntzer³

et al. 2009

Journal of Neuroscience Methods

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Calibration of physical dissector method Computer ganglion model Total number of sensory neurons Dorsal root ganglia a b s t r a c tThe physical disector is a method of choice for estimating unbiased neuron numbers; nevertheless, calibration is needed to evaluate each counting method. The validity of this method can be assessed by comparing the estimated cell number with the true number determined by a direct counting method in serial sections. We reconstructed a 1/5 of rat lumbar dorsal root ganglia taken from two experimental conditions. From each ganglion, images of 200 adjacent semi-thin sections were used to reconstruct a volumetric dataset (stack of voxels). On these stacks the number of sensory neurons was estimated and counted respectively by physical disector and direct counting methods. Also, using the coordinates of nuclei from the direct counting, we simulate, by a Matlab program, disector pairs separated by increasing distances in a ganglion model. The comparison between the results of these approaches clearly demonstrates that the physical disector method provides a valid and reliable estimate of the number of sensory neurons only when the distance between the consecutive disector pairs is 60 m or smaller. In these conditions the size of error between the results of physical disector and direct counting does not exceed 6%. In contrast when the distance between two pairs is larger than 60 m (70-200 m) the size of error increases rapidly to 27%.We conclude that the physical dissector method provides a reliable estimate of the number of rat sensory neurons only when the separating distance between the consecutive dissector pairs is no larger than 60 m.

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Role of thyroid hormones and their receptors in peripheral nerve regeneration

Cited by 44 publications

References 109 publications

Etifoxine promotes glial-derived neurotrophic factor-induced neurite outgrowth in PC12 cells

Etifoxine promotes glial-derived neurotrophic factor-induced neurite outgrowth in PC12 cells

Induction of Type 2 Iodothyronine Deiodinase in Astrocytes after Transient Focal Cerebral Ischemia in the Rat

Does the physical disector method provide an accurate estimation of sensory neuron number in rat dorsal root ganglia?

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