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The aim of this study was to determine whether chronic administration of GnRH improves performance of learning tasks and expression of spinophilin in the hippocampus of gonadectomized old rats. Eighteen-month-old male Wistar rats were used and divided into three groups: control (intact rats); gonadectomized; and gonadectomized + GnRH. The latter group was injected intramuscularly with GnRH (100 nM) twice a day for five weeks. The learning tasks we used were the novel object recognition task (NOR), elevated T-maze (ETM) and active avoidance test (AAT). Results showed that in NOR and ETM learning tasks, gonadectomized rats treated with GnRH had a significantly better performance than gonadectomized rats without treatment. GnRH-treated gonadectomized rats displayed performance comparable to that of intact rats. Furthermore, the expression of spinophilin in the hippocampus of gonadectomized rats treated with GnRH increased with respect to untreated gonadectomized rats. In conclusion, the chronic administration of GnRH improves learning in old gonadectomized rats. It is possible that the mechanism could involve a greater number of dendritic contacts associated with a higher expression of spinophilin.

Electromyographic studies have shown that external anal sphincter activity is modified in response to distension in animals with spinal cord injury. Gonadotropin-releasing hormone and its agonist leuprolide acetate have neurotrophic properties in animals with spinal cord injury. This study was to determine the effects of leuprolide acetate treatment on electromyographic activity of the external anal sphincter and anorectal manometry in ovariectomized rats with spinal cord injury. Adult ovariectomized rats were divided in three groups: (a) sham of spinal cord injury, (b) spinal cord injury treated with saline solution, and (c) spinal cord injury treated with leuprolide acetate. The spinal cord injury was induced by clamping at level T9. Leuprolide acetate dosage of 10 μg/kg was proctored intramuscular for 5 weeks, commencing the day after the lesion. Electromyography of the external anal sphincter, anorectal manometry, and volume of the cecum were evaluated in all groups. The electromyographic study of the external anal sphincter activity showed a significant improvement in injured rats treated with leuprolide acetate. Manometric analysis and cecum volume data obtained in animals with leuprolide acetate were very similar to those found in the sham group. These results demonstrate that leuprolide acetate treatment improves the neurogenic colon in ovariectomized rats with spinal cord injury.

It has been reported that the Gonadotropin-releasing hormone (GnRH) and its agonist leuprolide acetate (LA) can act as promoters of nerve regeneration. The aim of this study is to evaluate the effect of LA in a complete transection model. Sciatic nerve injury (SNI) was performed using a complete nerve transection and immediately repaired by epineural sutures. Rats were divided into three groups: SHAM, SNI treated with LA (SNI + LA) or saline solution (SNI + SS) for 5 weeks. Sciatic nerve regeneration was evaluated by kinematic gait analyzes, electrophysiological, morphological and biochemical tests. SNI + LA group had a functional recovery in kinematic gait, an increase in ankle angle value and a faster walking speed, compound muscle action potential amplitude, nerve conduction velocity (NCV). Furthermore, the number of myelinated axons and microtubule-associated protein 2 (MAP-2) expression were also higher compared to SS group. In conclusion, LA treatment improves of gait, walking speed, NCV, axons morphometry and MAP-2 expression in rats with sciatic nerve complete transection. These results suggest that LA can be a potential treatment for peripheral nerve injuries.

It has been previously described the presence of GnRH receptor in spinal cord neurons of rat embryos and adult rats. However, the functional role of these receptors has not been studied. In this work, the effect of GnRH on neurite outgrowth and cytoskeletal protein expression in cultured spinal cord neurons of rat embryos was analyzed. Specifically, neurofilaments of 68 and 200 kDa by immunoblot assays and spinophilin mRNA expression by RT-PCR. Results show that GnRH stimulates neurite outgrowth in addition to an increase in neurofilaments and spinophilin expression. These findings suggest that GnRH may play a role as neuromodulator in neuronal plasticity and that could be considered as a potential factor for neuronal regeneration in spinal cord injuries.

Gonadotropin-releasing hormone (GnRH) and GnRH receptor are produced locally by immune cells, suggesting an autocrine or paracrine role for GnRH within the immune system. The lymphocytes (T, B and NK cells), monocytes, macrophages, neutrophils, eosinophils and mast cells are affected directly or indirectly by GnRH. GnRH or GnRH agonists regulate immune cells, the expression of various receptors, cell proliferation, IFN secretion, the adhesion proteins of extracellular matrix, chemotactic migration, the cell cytotoxicity, and angiogenic chemokines. IL-4 production is suppressed and both nitric oxide and nuclear factor-kappa B are inhibited. Furthermore, GnRH has been reported to exacerbate the responses in autoimmune diseases such as systemic lupus erythematosus, autoimmune thyroiditis and autoimmune diabetes. However, GnRH administration reduces the severity of experimental autoimmune encephalomyelitis. Thus, GnRH may modulate multiple functions involved in the immune system through the integration of a set of homeostatic mechanisms.

Mammalian gonadotropin-releasing hormone (GnRH) and its receptor have been found in the neuroendocrine reproductive axis. However, they can be localized in other extra-pituitary tissues as well including the central nervous system. The present study reports the expression of GnRH receptor and its mRNA in spinal cord neurons of rat embryos and adult rats, using immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemistry showed that the spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor. The study of GnRH receptor mRNAs revealed that both cultured spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor mRNA. Additional in vitro experiments showed that the expression of GnRH receptor mRNA was less in the spinal cord neurons exposed to GnRH compared to unexposed ones. These results raise the possibility that GnRH may play other roles independently from its participation in reproductive function.

The presence of GnRH receptor in cerebral cortical neurons of rat embryos and adult rats has been described. In this work, we studied the effects of GnRH on outgrowth and length of neurites and cytoskeletal neurofilament proteins expression (NF-68 and NF-200 kDa) by immunoblot of cultured cerebral cortical neurons of rat embryos. Our results show that GnRH increases both outgrowth and length of neurites accompanied by an increase in neurofilaments expression. It is conceivable that GnRH plays a role in neuronal plasticity parallel to its gonadal function.

Several studies have shown that gonadotropin-releasing hormone (GnRH) have extra-pituitary roles, including neurotrophic effects. This study was to evaluate the effects of GnRH treatment on the spinal cord injury (SCI) of rats. Ovariectomized rats were divided into: sham SCI surgery (Sham), SCI treated with saline solution (SCI + SS), and SCI treated with GnRH (SCI + GnRH). The SCI was induced by compression. One day after the lesion, SCI + GnRH group was injected with GnRH (60 µg/kg/twice/day; i.m.) for 15 days and the other groups with saline solution. To kinematic gait analysis, length and velocity of the stride were measured. In spinal cord, axonal morphometry and spared white and gray matter were analyzed by histochemistry. Protein expression of spinophilin was evaluated by western blot. The results showed that, 5 weeks after the injury, the group of animals treated with GnRH, significantly increased the length and velocity of the stride compared to SCI + SS group and they were similar to Sham group. In spinal cord, GnRH treatment increased the number and caliber of nerve axons and in the case of white matter, spared tissue was significantly higher than those animals treated with saline solution. The expression of spinophilin in spinal cord of SCI + GnRH group was slightly increased with respect to those not treated. In conclusion, GnRH treatment improves recovery of gait and decreases histopathological damage in the injured spinal cord of rat. These findings suggest that GnRH acts as a neurotrophic factor and can be used as a potential therapeutic agent for treatment of SCI.

Gonadotrophin-releasing hormone (GnRH), a well known hypothalamic neuropeptide, has been reported to possess neurotrophic properties. Leuprolide acetate, a synthetic analogue of GnRH is considered to be a very safe and tolerable drug and it has been used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. The present study was designed to determine whether Leuprolide acetate administration, exerts neurotrophic effects on clinical signs, body weight gain, neurofilaments (NFs) and myelin basic protein (MBP) expression, axonal morphometry and cell infiltration in spinal cord of experimental autoimmune encephalomyelitis (EAE) rats. In this work, we have found that Leuprolide acetate treatment decreases the severity of clinical signs of locomotion, induces a significantly greater body weight gain, increases the MBP and NFs expression, axonal area and cell infiltration in EAE animals. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.

It was reported that the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH) produces neurotrophic effects and that the spinal cord possesses GnRH receptors. The aim of the present study was to determine whether administration of GnRH improves locomotor activity, urinary function and neurofilament (NFs) protein expression after spinal cord injury (SCI) in ovariectomized rats. SCI was induced by balloon inflation model resulting in paraplegia. Locomotion was evaluated according to the Basso, Beattie, and Bresnahan Scale. Rats were subjected to bladder compression, twice daily until bladder reflex was established. NFs of 68, 160 and 200 kDa from spinal cords were analyzed by electrophoresis. GnRH (60 μg/kg) or physiologic NaCl solution was administered at 1 day after SCI and then daily for 15 days and the functional evaluation was realized for 5 weeks. Our results indicate that locomotor activity, restoration of urinary dysfunction and NFs expression of 160 and 200 kDa were improved in SCI animals given GnRH compared to those without treatment. These findings suggest that GnRH acts as a neurotrophic factor and may be used as a potential therapeutic agent for treatment of SCI.

It has been reported that the spinal cord possesses Gonadotropin-releasing hormone (GnRH) receptor and that GnRH has neurotrophic properties. Experimental autoimmune encephalomyelitis (EAE) causes neurodegeneration in spinal cord. Thus, the present study was designed to determine whether administration of GnRH reduces the severity of EAE. The clinical signs of locomotion, axonal morphometry and neurofilaments (NFs) expression were evaluated. Clinical signs remained significantly lower in EAE rats with GnRH administration compared to animals without treatment. Morphometric analysis, there were more axons of larger areas in the spinal cord of EAE + GnRH group compared to EAE animals. Western blot analysis demonstrated that GnRH administration significantly increased the expression of NFs of 68, 160 and 200 kDa in the spinal cord of EAE animals. Our results indicate that GnRH administration reduces the severity of EAE in the rat.

The protein SNAP-25 is located in the plasma membrane and is known to participate in hormone exocytosis process. In the present work we studied the role of SNAP-25 on LH secretion in permeabilized adenohypophyseal cultured cells. The question of whether GnRH regulates SNAP-25 expression in adenohypophyseal cultured cells and in the adenohypophyses in vivo was also investigated.In digitonin-permeabilized cells incubated with anti-SNAP-25, stimulated LH secretion with Ca2+ was analysed. The presence and expression of SNAP-25 in adenohypophyseal cultured cells incubated with GnRH and in adenohypophyses of orchidectomized rats with GnRH administration was studied by immunochemistry and immunoblotting.Immunochemical study revealed that SNAP-25 was present in cultured adenohypophyseal cells and in adenohypophysis of orchidectomized rats both with GnRH treatment. We found that LH secretion can be blocked by antibodies raised against SNAP-25 in permeabilized cells. Likewise, GnRH administration induced a significant decrease of SNAP-25 expression in cultured adenohypophyseal cells and in adenohypophysis of orchidectomized rats.Our study showed that SNAP-25 is present in adenohypophyses in vitro as well as in vivo and that is involved in LH release and that GnRH can modify its expression.