The effects of the combination of temozolomide and Eribulin on T98G human glioblastoma cell line: an ultrastructural study.

Glioblastoma tumors are the most aggressive primary brain tumors that develop resistance to temozolomide (TMZ). Eribulin (ERB) exhibits a unique mechanism of action by inhibiting microtubule dynamics during the G2/M cell cycle phase. We utilized the T98G human glioma cell line to investigate the effects of ERB and TMZ, both individually and in combination. The experimental groups were established as follows: control, E5 (5 nM ERB), T0.75 (0.75 mM TMZ), T1 (1.0 mM TMZ), and combination groups (E5+T0.75 and E5+T1). All groups showed a significant decrease in cell proliferation. Apoptotic markers revealed a time-dependent increase in annexin-V expression, across all treatment groups at the 48-hour time point. Caspase-3, exhibited an increase in the combination treatment groups at the 48-hour mark. Transmission electron microscopy (TEM) revealed normal ultrastructural features in the glioma cells of the control group. However, treatments induced ultrastructural changes within the spheroid glioblastoma model, particularly in the combination groups. These changes included a dose-dependent increase in autophagic vacuoles and apoptotic morphology of the cells. In conclusion, the similarity in the mechanism of action between ERB and TMZ suggests the potential for synergistic effects when combined. Our results highlight that this combination induced severe damage and autophagy in glioma spheroids after 48 hours.

Expression of brain-derived neurotrophic factor and formation of migrasome increases in the glioma cells induced by the adipokinetic hormone.

OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 µM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.

Effect of sugammadex, rocuronium and sevoflurane on oxidative stress and apoptosis in cerebral ischemia reperfusion model in rats.

OBJECTIVE: Cerebral ischemia-reperfusion (I/R) injury causes neurological dysfunction and cell death. Sugammadex, as a large molecule, is normally difficult to pass through the blood-brain barrier (BBB). In ischemia, molecules can pass into the brain tissue. In this study, we aimed to evaluate the effect of sugammadex in the presence of cerebral I/R damage in rats with a general anesthesia model with sevoflurane and rocuronium. METHODS: Rats were divided into 7 groups; Group 1 (Control), Group 2 (Sham), Group 3 (Sevoflurane), Group 4 (Sugammadex), Group 5 (Sevoflurane + Rocuronium), Group 6 (Sevoflurane + Sugammadex), Group 7 (Sevoflurane + Rocuronium + Sugammadex). Brain tissues of rats with cerebral I/R damage with bilateral carotid occlusion were removed. Tissue Malondialdehyde (MDA), Myeloperoxidase (MPO), and Superoxide dismutase (SOD) levels were examined with ELISA and apoptosis was examined by Caspase-3. RESULTS: The number of caspase-3 positive cells decreased the most in Group 4 compared to the other groups. Group 4's mean MDA and MPO levels were lower than Group 2. There was no significant difference in terms of SOD levels. CONCLUSION: The apoptotic effect of sugammadex was lowest compared to other agent groups, and it did not increase oxidative damage as much as the other groups.

Expression of brain-derived neurotrophic factor and formation of migrasome increases in the glioma cells induced by the adipokinetic hormone

SUMMARY OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 μM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.

Investigation of Demyelination and Remyelination Processes of the Compressed Optic Chiasm: An Experimental Model.

AIM: To demonstrated demyelination and remyelination of the optic nerve histologically by electron microscopy in an experimental model similar to the compression of pituitary adenomas on the optic chiasm. MATERIAL AND METHODS: The rats were fixed to a stereotaxic device under deep anesthesia, and a balloon catheter was placed under the optic chiasm through a burr hole which was in front of the bregma in accordance with the brain atlas of rats. The animals were divided into five groups (n=8): control, mild compression demyelination, severe compression demyelination, mild compression remyelination, severe compression remyelination. The fine structures of the tissues obtained were evaluated using electron microscopy. RESULTS: We found a significant difference in the severity of degeneration when comparing group 1 with group 5 (p < 0.001); there was no degeneration in group 1 rats and severe degeneration in all of the group 5 rats. Oligodendrocytes were found in all rats in group 1 and none of the rats in no group 2. The nuclei were preserved in the group 1 rats but damaged in all of the group 5 rats. There were no lymphocytes or erythrocytes in group 1 and all positives in group 5. CONCLUSION: This technique, which induced degeneration without causing damage to the optic nerve with toxic or chemical agents, revealed Wallerian degeneration similar to tumoral compression. After compression relief, the optic nerve remyelination process can be better understood, particularly for sellar lesions. In our opinion, this model may guide future experiments to identify protocols to induce and accelerate remyelination.

Neonatal Tactile Stimulation Downregulates Dendritic Spines in Layer V Pyramidal Neurons of the WAG/Rij Rat Somatosensory Cortex.

Objective: The aim of our study is to examine the effects of neonatal tactile stimulations on the brain structures that previously defined as the focus of epilepsy in the Wistar-Albino-Glaxo from Rijswijk (WAG/Rij) rat brain with genetic absence epilepsy. Methods: In the present research, morphology and density of dendritic spines were analyzed in layer V pyramidal neurons of the somatosensory cortex (SoCx) of WAG/Rij rats (nonstimulated control, tactile-stimulated, and maternal separated rats) and healthy Wistar (nonepileptic) rats. To achieve this, a Golgi-Cox method was used. Results: Dendritic spine number in layer V of the SoCx has been detected significantly higher in adult WAG/Rij rats at postnatal day 150 in comparison to nonepileptic adult control Wistar rats (p < 0.001). Moreover, quantitative analyses of dendrite structure in adult WAG/Rij rats showed a decrease in dendrite spine density of pyramidal neurons of SoCx which occurred in early neonatal exposure to maternal separation (MS) and tactile stimulation (TS) (p < 0.001). Conclusions: Our findings provide the first evidence that tactile stimulations during the early postnatal period have a long-term impact on dendrite structure in WAG/Rij rat's brain and demonstrate that neonatal tactile stimulation can regulate dendritic spines in layer V in pyramidal neurons of SoCx in epileptic brains.

Anatomic and histologic features of diaphragma sellae that effects the suprasellar extension.

This study aimed to determine the anatomical and histological features of diaphragma sellae that affect the suprasellar extension of intrasellar tumours. Twenty-four fresh adult cadavers were dissected for the study. Diaphragma sellae and pituitary capsules with sellar structures were resected. The diaphragma sellae was anatomically reviewed in detail. Immunohistochemical staining was performed for collagen types I, II, III, and IV. We examined the suprasellar growth of 13 sellar tumours extending superiorly through the diaphragma sellae by performing a series of 2704 endoscopic transnasal operations to analyse the anatomic and histologic results of the study. The diameter of the foramen of diaphragma sellae varied between specimens. Of 24 specimens, the diaphragma sellae in five (21%) had a tight-type foramen and those in 19 (79%) were more spacious. An increased expression of collagen types I and IV was observed in the pituitary capsule and the diaphragma sellae. In this clinical series, we observed that all types of sellar tumours could expand through the foramen. We observed radiologically and intraoperatively that the diaphragma sellae was displaced laterally and formed a dome in two cases with an adenoma extending to the suprasellar area. Two types of suprasellar extension through the diaphragma sellae are possible: 1) The collagen structure of diaphragma sellae can be destroyed by invasive tumours; 2) The morphology of the foramen of the diaphragma sellae facilitates suprasellar tumoural extension. All sellar tumours, including non-invasive cystic tumours, may invade the suprasellar area by expanding through the foramen of the diaphragma sellae.

Positive outcomes of phosphodiesterase type 5 inhibitor on histopathologic and biochemical changes induced by ureteral obstruction.

OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss.The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-ß (TGF-ß) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-ß decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-ß in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

Positive outcomes of phosphodiesterase type 5 inhibitor on histopathologic and biochemical changes induced by ureteral obstruction

SUMMARY OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

RESUMO OBJETIVOS: Examinamos os efeitos do tadalafil em um dos inibidores da fosfodiesterase tipo 5 (PDE5) em um modelo de rato com obstrução ureteral unilateral parcial e completa (UUO). MÉTODOS: Os ratos foram divididos em cinco grupos: sham (n = 6), obstrução ureteral unilateral parcial (PUUO, n = 6), PUUO com tadalafil (PUUO T; Cialis, 10 mg/72 h, intragástrica; Lilly, Indianapolis, Indiana, EUA), completa obstrução ureteral unilateral (CUUO, n = 6) e CUUO com tratamento com tadalafil (CUUO T). RESULTADOS: Quinze dias após a UUO, o ureter apresentou alterações nas camadas de urotélio e infiltração significativa de células inflamatórias nos grupos PUUO e CUUO. Em comparação com os grupos sham, PUUO e CUUO, houve um aumento grave da infiltração de células inflamatórias. O epitélio urotelial exibiu degeneração e perda celular devido às células epiteliais inchadas, atróficas e desnudas nos grupos PUUO e CUUO. Nos grupos PUUO T e CUUO T, o urotélio revelou menor degeneração e perda de células epiteliais. Nós mostramos que a expressão da actina do músculo liso-α (α-SMA) e do fator de crescimento transformador-β (TGF-β) foram exibidas como sub-regulação nos grupos PUUO e CUUO. A expressão do TGF-β foi diminuída positivamente correlacionada com a da α-SMA nos grupos de terapia com tadalafil, PUUO T e CUUO T. CONCLUSÃO: O tadalafil do inibidor da fosfodiesterase tipo 5 reduziu as expressões α-SMA e TGF-β nos ureteres obstruídos, medidos por exames bioquímicos. Além disso, o tadalafil diminuiu a degeneração do urotélio devido à diminuição da perda de células epiteliais e da infiltração de células inflamatórias. Nossos resultados mostram que o tadalafil previne ou retarda o início da inflamação do ureter e degeneração urotelial em ratos com UUO.

Effects of Asenapine and Paliperidone on Depression, Anxiety and Analgesy in Mice: Alterations in Brain Neurotrophic Factors, Neurogenesis, and Blood Enzyme Levels.

Schizophrenia, an important brain neurodevelopmental disorder, is observed in 1% of the global population. New-generation antipsychotics have been developed as alternatives to typical antipsychotics for more effective and safe therapy. Chronic administration of asenapine and paliperidone compared to haloperidol on depression, anxiety and analgesy in the forced swimming test (FST), elevated plus maze (EPM) and hot plate tests were examined in mice. Moreover effects of drugs, on expression levels of brain neurotrophic factors [brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB),nerve growth factor (NGF), synapsin and fibroblast growth factor 2 (FGF2)] in the hippocampus of mice, neurogenesis and neurodegeneration, and blood enzyme levels were also investigated. In FST, haloperidol (0.25 mg/kg) significantly increased immobility time while both asenapine (0.075 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly diminished this parameter. In EPM test, haloperidol significantly increased both % time spent in open arms and % open arm entries. Asenapine (0.075 mg/kg) and paliperidone (0.50 mg/kg) significantly increased % time spent in the open arms. They also increased % open arm entries, but this parameter failed to reach a statistically significant value. In hot plate test, haloperidol (0.125 and 0.25 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly increased the latency to lick the hind paws but asenapine had no effect. Asenapine and paliperidone upregulated more neurotrophic factors in the brain and caused less neurodegeneration compared to haloperidol. Investigated drugs had no effect on liver enzymes and plasma glucose levels. Asenapine and paliperidone may be preferred over classical antipsychotics since they have antidepressant-like effect, upregulate more neurotrophic factors and cause less neurodegeneration in naive mice without having diabetogenic and liver damaging effects. Paliperidone seems to possess superior effects compared to asenapine since it also exerts analgesic-like effect.

The relationship between glomerular function and podocyte structure of pre-proteinuria and acute nephrosis in puromycin aminonucleoside-induced rat models: a comparative electron microscopic study.

Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.

The effect of tadalafil therapy on kidney damage caused by sepsis in a polymicrobial septic model induced in rats: a biochemical and histopathological study

ABSTRACT Introduction Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). Materials and Methods Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. Results Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p<0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p<0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p<0.05). Conclusion In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.

The effect of tadalafil therapy on kidney damage caused by sepsis in a polymicrobial septic model induced in rats: a biochemical and histopathological study.

INTRODUCTION: Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). MATERIALS AND METHODS: Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. RESULTS: Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p < 0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p < 0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p < 0.05). CONCLUSION: In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.

Effects of a dragonfly (Anax i.) homeopathic remedy on learning, memory and cell morphology in mice.

BACKGROUND: Homeopathy is a form of alternative medicine in which uses highly diluted preparations that are believed to cause healthy people to exhibit symptoms similar to those exhibited by patients. The aim of this study was to investigate the effects of dragonfly (Anax imperator, Anax i.) on learning and memory in naive mice using the Morris water maze (MWM) test; moreover, the effects of dragonfly on MK-801-induced cognitive dysfunction were evaluated. METHODS: Male balb-c mice were treated with dragonfly (30C and 200C) or MK-801 (0.2 mg/kg) alone or concurrently (n = 10). Dragonfly (D) and MK-801 were administered subchronically for 6 days intraperitoneally 60 min and 30 min, respectively, before the daily performance of the MWM test. RESULTS: This study revealed that in the familiarization session and first session of the MWM test, Anax i. D30 significantly decreased escape latency compared to the control group, although MK-801, D30 and D200 significantly increased escape latency at the end of five acquisition sessions. Anax i. combined with dizocilpine maleate (MK-801) also significantly decreased escape latency in the familiarization session and first session of the MWM test, although this combination increased escape latency compared to the MK-801 alone group at the end of the test. Time spent in escape platform's quadrant in the probe trial significantly decreased while mean distance to platform significantly increased in MK-801, D30 and D200 groups. In the MWM test, Anax i. combined with MK-801 significantly decreased speed of the animals compared to the MK-801 alone group. General cell morphology was disturbed in the MK-801 group while D30 and D200 seemed to improve cell damage in the MK-801 group. CONCLUSIONS: These results suggest that the homeopathic Anax i. can impair learning acquisition and reference memory, and it has beneficial effects on disturbed cell morphology.

Effects of chronic administration of adipokinetic and hypertrehalosemic hormone on animal behavior, BDNF, and CREB expression in the hippocampus and neurogenesis in mice.

Neurosecretory cells in corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosaemic or hyperprolinaemic, depending on insect in question. This study investigated effects of chronic administration of Anax imperator adipokinetic hormone (Ani-AKH), Libellula auripennis adipokinetic hormone (Lia-AKH), and Phormia-Terra hypertrehalosaemic hormone (Pht-HrTH) on depression, anxiety, analgesy, locomotion in forced swimming (FST), elevated plus-maze (EPM), hot plate, and locomotor activity tests. Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH (1 and 2 mg/kg) had antidepressant effects in forced swimming test. Lia-AKH (2 mg/kg) and Pht-HrTH (1 and 2 mg/kg) had anxiolytic effects when given chronically in elevated plus-maze test. Ani-AKH (1 and 2 mg/kg) and Pht-HrTH (2 mg/kg) had antinociceptive effects in hot plate test in male balb-c mice. Ani-AKH (2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH had locomotion-enhancing effects in locomotor activity test in male balb-c mice. Drug treatment significantly increased brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) gene expression levels compared to control levels. Pht-HrTH and Ani-AKH groups had significantly increased numbers of BrdU-labeled cells, while neurodegeneration was lower in the Pht-HrTH group. Our study showed that AKH/RPCH family peptides may be used in treatment of psychiatric illness such as depression and anxiety, in treatment of pain and in diseases related to locomotion system. AKH/RPCH family peptides increase neurotrophic factors in brain and have potential proliferative and neuroprotective effects in hippocampal neurogenesis and neurodegeneration.

Effects of homeopathic Anax imperator on behavioural and pain models in mice.

BACKGOUND: Homeopathy is a medical theory and practice that asserts that disease can be cured by remedies that produce symptoms in a healthy person similar to those suffered by a patient with a malady. METHODS: The aim of this study was to investigate effects of homeopathic Anax imperator (dragonfly) (Anax-i 30c and Anax-i 200c) in the forced swim test (FST), elevated plus-maze (EPM) test, hot plate (HP) test and open field test and examined NPY1 receptor expression, in naive mice. RESULTS: In the FST, treatment with Anax-i 30c or Anax-i 200c significantly diminished immobility time while in EPM test, Anax-i 200c increased the percentage of time spent in open arms as well as the percentage of open arm/total arms. In the HP test, Anax-i 30c or Anax-i 200c decreased the total time mice spent licking their hind paws while in open field test, treatment with Anax-i 200c increased the total distance and speed mice traveled compared to the control group. Three weeks of daily injections with Anax-i 30c or Anax-i 200c caused significant weight loss in mice. Anax-i 30c or Anax-i 200c treatment significantly decreased NPY1 receptor expression, and Anax-i 30c also decreased NPY2 receptor expression. CONCLUSION: These results suggest that the homeopathic Anax-i exerts antidepressant, anxiolytic and analgesic-like effects and causes hyperlocomotion and weight loss.

The effect of etanercept and methylprednisolone on functional recovery of the facial nerve after crush injury.

OBJECTIVE: To establish whether etanercept, a TNF-α antagonist, is an alternative and effective treatment on facial nerve after crush injury. METHOD: Fifty-four rats underwent exposure of the left main trunk of the facial nerve followed by a standard crush injury. Animals were randomly divided into 3 groups: control group, methylprednisolone-treated group, and etanercept-treated group. All these groups were divided into 2 subgroups; animals were sacrificed on the 4th day after facial crush injury in the first subgroup and on the 28th day in the second subgroup. Functional recovery of vibrissae movement, eye blink reflex, and vibrissae orientation was measured on a 3-point scale (1 = no recovery, 2 = partial recovery, and 3 = complete recovery) during the recovery process. Facial nerve, from the main trunk at the stylomastoid foramen to the zygomatic, buccal, and marginal branches, were dissected and postfixed in the same fixative. The paraffin sections were studied with macrophage marker, GAP-43 and T Cell Marker. RESULTS: Animals receiving etanercept demonstrated significantly better functional recovery compared with control and methylprednisolone-treated animals. The etanercept-treated group showed highest GAP-43 immunoreactivity in the nerves. After the macrophage marker and T cell marker staining, the etanercept and methylprednisolone groups demonstrated statistically significant difference compared with the control group (p < 0.001). CONCLUSION: The present study demonstrates accelerated functional recovery associated with etanercept treatment after facial nerve crush injury in rats.

Effect of Lycopersicon esculentum extract on apoptosis in the rat cerebellum, following prenatal and postnatal exposure to an electromagnetic field.

The expansion of mobile phone technology has raised concerns regarding the effect of 900-MHz electromagnetic field (EMF) exposure on the central nervous system. At present, the developing human brain is regularly exposed to mobile telephones, pre- and postnatally. Several studies have demonstrated the acute effects of EMF exposure during pre- or postnatal periods; however, the chronic effects of EMF exposure are less understood. Thus, the aim of the present study was to determine the chronic effects of EMF on the pre- and postnatal rat cerebellum. The control group was maintained in the same conditions as the experimental groups, without the exposure to EMF. In the EMF1 group, the rats were exposed to EMF during pre- and postnatal periods (until postnatal day 80). In the EMF2 group, the rats were also exposed to EMF pre- and postnatally; in addition, however, they were provided with a daily oral supplementation of Lycopersicon esculentum extract (∼2 g/kg). The number of caspase-3-labeled Purkinje neurons and granule cells present in the rats in the control and experimental groups were then counted. The neurodegenerative changes were studied using cresyl violet staining, and these changes were evaluated. In comparison with the control animals, the EMF1 group demonstrated a significant increase in the number of caspase-3-labeled Purkinje neurons and granule cells present in the cerebellum (P<0.001). However, in comparison with the EMF1 group, the EMF2 group exhibited significantly fewer caspase-3-labeled Purkinje neurons and granule cells in the cerebellum. In the EMF1 group, the Purkinje neurons were revealed to have undergone dark neuron degenerative changes. However, the presence of dark Purkinje neurons was reduced in the EMF2 group, compared with the EMF1 group. The results indicated that apoptosis and neurodegeneration in rats exposed to EMF during pre- and postnatal periods may be reduced with Lycopersicon esculentum extract therapy.

Morinda citrifolia L. (noni) and memantine attenuate periventricular tissue injury of the fourth ventricle in hydrocephalic rabbits.

This study was designed to evaluate the neuroprotective effects of Morinda citrifolia L. (Rubiaceae), commonly known as noni, and memantine (a N-methy-D-aspartate receptor inhibitor) on hydrocephalus-induced neurodegenerative disorders. Kaolin was injected into the cistern magna of male adult New Zealand rabbits to establish a hydrocephalus animal model. Memantine (20 mg/kg, intraperitoneally; memantine-treated group) or noni (5 mL/kg, intragastrically; noni-treated group) was administered daily for 2 weeks. Microtubule-associated protein-2 and caspase-3 immunohistochemistry were performed to detect neuronal degeneration and apoptosis in the periventricular tissue of the fourth ventricle of rabbits. Microtubule-associated protein-2 staining density was significantly decreased in the hydrocephalic group, while the staining density was significantly increased in the memantine- and noni-treated groups, especially in the noni-treated group. Noni treatment decreased the number of caspase-3-positive cells in rabbits with hydrocephalus, while memantine had no effect. These findings suggest that noni exhibits more obvious inhibitory effects on hydrocephalus-induced neurodegenerative disorders than memantine in periventricular tissue of the fourth ventricle.

Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice.

AIMS: Tianeptine is an atypical antidepressant drug that has a different mechanism of action than other antidepressants. Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia. The present study was undertaken to investigate effects of chronic administration of tianeptine or olanzapine on unpredictable chronic mild stress (UCMS)-induced depression-like behavior in mice compared to a widely used SSRI antidepressant, fluoxetine. MAIN METHODS: Male inbred BALB/c mice were subjected to different kinds of stressors several times a day for 7weeks and were treated intraperitoneally with tianeptine (5mg/kg), olanzapine (2.5mg/kg), fluoxetine (15mg/kg) or vehicle for 5weeks (n=7-8 per group). KEY FINDINGS: All the drugs tested prevented stress-induced deficit in coat state during UCMS procedure, in grooming behavior in the splash test, decreased the attack frequency in the resident intruder test and decreased the immobility time in the tail suspension test. In the open field test olanzapine had anxiolytic-like effects in both stressed and non-stressed mice. Tianeptine, olanzapine and fluoxetine decreased the enhanced levels of plasma ACTH and IL-6. Chronic treatment with tianeptine resulted in a significant increase in both total number and density of BrdU-labeled cells in stressed animals, while fluoxetine and olanzapine had a partial effect. SIGNIFICANCE: The results of this study support the hypothesis that tianeptine can be as effective as fluoxetine for the treatment of depression in spite of the differences in the mechanism of action of these drugs. Moreover, olanzapine could be used effectively in psychotic patients with depression.