Journal of chemical neuroanatomy最新文献

Aim

Gamma radiation, a form of ionizing radiation, is used in many different areas, especially in the health field and in the treatment of cancer. However, gamma radiation used for therapeutic purposes also has numerous harmful effects on human health. This study was planned to investigate the impacts of exposure to gamma radiation on the hippocampal area and the preventive effects of myricitrin and chebulinic acid against that damage.

Material and method

Thirty-six male Wistar albino rats were randomly divided into six groups. The control group was exposed to no treatment. The chebulinic acid and myricitrin groups were injected with the relevant drug at a dosage of 0.033 mg/kg) (vehicle; normal saline) per day. The gamma groups were placed in a plexiglass test setup with their heads positioned close to the source. The subjects were exposed to radiation with a mixed source containing radioactive Cs-137 and Co-60 isotopes obtained from Ondokuz Mayıs University Physics Department Nuclear Physics Laboratory for 1 h. Gamma radiation was applied 16 mGy for one hour per day for 10 days. The gamma radiation+chebulinic acid and the gamma radiation myricitrin groups also received 0.033 mg/kg per day of these drugs via injection. Immediately after the experimental procedure, all animals were subjected to behavioural tests, and perfused brain tissues were analyzed using stereological methods.

Results

Stereological analysis showed that gamma radiation caused a decrease in the numbers of neurons in the hippocampal area (p < 0.01; One-way ANOVA) and that chebulinic acid and myricitrin reduced this decrease (p < 0.01; One-way ANOVA). Decreases in learning and memory capacity were detected in behavioural tests in rats from the Gamma group.

Conclusion

The study findings showed that that the adverse health effects of Gamma radiation can be ameliorated using myricitrin and chebulinic acid. Myricitrin was more effective in terms of cell proliferation and defence against oxidative stress than chebulinic acid, and exhibited a more neuroprotective effect. However, more detailed analyses should be performed before using either antioxidant for therapeutic purposes.

Background

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. Lacosamide, an anti-epileptic drug, has shown promising results in preclinical studies as a potential neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD.

Methods

Twenty-one adult male rats were randomly divided into the following three groups (n = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, immunohistochemistry and biochemistry were used to assess the dopaminergic neuron loss in the substantia nigra and MDA, TNF-α and HVA levels, respectively.

Results

In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function.

Conclusion

In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.

Tramadol is analgesic medication to relief acute and chronic pain, referred to as alternative to opioid drugs however its abuse or overdosage may resulted in neuronal toxicity. This is attributed to severe fluctuations of neurotransmitters pattern along with cerebral inflammation and oxidative damage. Present work was undertaken to illustrate the cytoprotective effect of 10-dehydrogingerdione (10-DHGD) on the brain tissues of experimental rats due to Tramadol intake and its underlying mechanism. 24 male wistar rats were randomized into 4 equal groups. Group (1), received tramadol in a dose level 20 mg/kg intrapertioneal (i.p) daily for 30 days and referred to Tramadol group. Group (2), received both of 10-DHGD (10 mg/kg, orally) one hour before tramadol intake (dose as mentioned before) daily for 30 days. Group (3) received 10-DHGD only (10 mg/kg, orally) and daily for 30 days. Group (4), received no drugs and referred to control group for comparison. Tramadol significantly reduced Norepinephrin (NE), dopamine, serotonin and glutathione (reduced) contents of Cerebral cortex. lipid peroxidation, nuclear factor kappa B (NFkB), inducible nitric oxide synthase (INOS) levels and caspase-3 immunoreactivity showed however significant increase. Of note, 10-DHGD significantly increased neurotransmitters, glutathione contents while Malondialdehyde (MDA), Nitric oxide (NO), NFkB, INOS additionally caspase-3 immunoexpression showed significant decrease i.e counteracted to certain extent tramadol effect. These findings may refer to the cytoprotective potential of 10-DHGD against the neurotoxicity exerted by tramadol intake, most probably mediated via enhancement of endogenous antioxidants system.

Background

Ethanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear.

Methods

Twenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups.

Results

While the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters.

Conclusion

The memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes.

Semaphorin 4 C (SEMA4C) and its cognate receptor Plexin B2 are important regulators of axon guidance and are involved in many neurological diseases, in which SEMA4C acts not only as a ligand ("forward" mode) but also as a signaling receptor ("reverse" mode). However, the role of SEMA4C/Plexin B2 in intracerebral hemorrhage (ICH) remains unclear. In this study, ICH in adult male Sprague-Dawley rats was induced by autologous blood injection in the right basal ganglia. In vitro, cultured primary neurons were subjected to OxyHb to imitate ICH injury. Recombinant SEMA4C (rSEMA4C) and overexpressing lentiviruses encoding full-length SEMA4C or secretory SEMA4C (sSEMA4C) were administered to rats by intraventricular injection. First, we found that elevated levels of sSEMA4C in the cerebrospinal fluid (CSF) of clinical patients were associated with poor prognosis. Both SEMA4C and sSEMA4C were increased in brain tissue around the hematoma after ICH in rats. Overexpression of SEMA4C attenuated neuronal apoptosis, neurosis, and neurologic impairment after ICH. However, treatment with rSEMA4C or sSEMA4C overexpression exacerbated neuronal injury. In addition, when treated with SEMA4C overexpression, the forward mode downstream protein RhoA and the reverse mode downstream ID1/3 transcriptional factors of SEMA4C/Plexin B2 signaling were all activated. Nevertheless, when exposed to rSEMA4C or sSEMA4C overexpression, only the forward mode was activated. Thus, sSEMA4C may be a novel molecular biomarker to predict the prognosis of patients with ICH, and the prevention of SEMA4C cleavage is expected to be a promising therapeutic target.

Gliomas are the highest prevalent primary central nervous system (CNS) cancers with poor overall survival rate. There is an urgent need to conduct more research into molecular therapies targeting critical elements of gliomas. This study herein targeted to assess the impact of tripartite motif protein 6 (TRIM6) on gliomas. Using public databases, we found the increased TRIM6 expression in tissues of glioma which was linked with worst overall survival. Silencing TRIM6 promoted glioma cell proliferation, migration and angiogenesis, suggesting the promoting effects of TRIM6 on gliomas. Knockdown of TRIM6 expression downregulated the expression levels of Forkhead box M1 (FOXM1) and vascular endothelial growth factor A (VEGFA) in glioma cells. Afterwards, impact of TRIM6 on VEGFA expression was regulated by FOXM1. VEGFA overexpression reversed the decreased abilities of glioma cell proliferation, migration and angiogenesis caused by silencing TRIM6. Furthermore, we also found that TRIM6 promoted the growth of gliomas in the xenograft mouse model. In summary, the expression of TRIM6 was increased which was related to poor prognosis of glioma patients. TRIM6 promoted glioma cell proliferation, migration and angiogenesis through the FOXM1-VEGFA pathway. Therefore, TRIM6 carries capacity to be explored as a novel therapeutic target in clinical.

Cisplatin is a chemotherapeutic agent usually used in treating different patterns of malignancies. One of the significant apparent complications of cisplatin chemotherapy is brain toxicity. The present study was conducted to evaluate the protective effects of lansoprazole on cisplatin-induced cortical intoxication. Thirty-two rats were allocated into four groups (8 rats/group); group I: received only a vehicle for 10 days, group II: lansoprazole was administered (50 mg/kg) via oral gavage for 10 days, group III: On 5th day of the experiment, rats were given cisplatin (10 mg/kg) i.p. once to induce cortical injury. Group IV: rats were given lansoprazole for 5 days before cisplatin and 5 days afterward. Lansoprazole administration significantly improved cisplatin-induced behavioral changes, as evidenced by decreasing the immobility time in forced swimming and open field tests. Besides, lansoprazole improved cortical histological changes, restored cortical redox balance, enhanced Nrf2/ARE expression, cisplatin-induced neuronal apoptosis, and dampened cisplatin inflammation. In addition, lansoprazole modulated cortical Akt/p53 signal. The present work was the first to show that lansoprazole co-administration reduced cortical toxicity in cisplatin-treated rats via multiple signaling pathways. The current findings provided crucial information for developing novel protective strategies to reduce cisplatin cortical toxicity.

The use of e-cigarettes/e-vapour, and the consumption of a high-fat diet (HFD), are two popular lifestyle choices associated with alterations in the hippocampus. This study, using a mouse model, investigated the effects of exposure to e-vapour ($\pm$ nicotine) and HFD (43% fat) consumption, on the expression of nicotinic acetylcholine receptor (nAChR) subunits $\alpha$3, $\alpha$4, $\alpha$7 and $\beta$2, apoptosis markers caspase-3 and TUNEL, microglial marker Iba-1, and astrocyte marker GFAP, in hippocampal subregions of dentate gyrus (DG) and cornu ammonis (CA) 1–3. The major findings included: (1) HFD alone had minimal effect with no consistent pattern or interaction between the markers, (2) E-vapour ($\pm$ nicotine) predominantly affected the CA2 subregion, decreasing α7 and β2 nAChR subunits and Iba-1, (3) Nicotine e-vapour increased TUNEL across all subregions, and (4) HFD, in the presence of nicotine-free e-vapour, decreased caspase-3 and increased TUNEL across all regions, and decreased Iba-1 in the CA subregions, while HFD and nicotine-containing e-vapour, subregion specifically affected the $\alpha$3, $\alpha$4 and $\alpha$7 nAChR subunits, with a protective effect against change in GFAP in the DG and Iba-1 in the CA1 and CA3. These findings highlight that e-vapour itself alters nAChRs, particularly in the CA2 subregion, associated with a decrease in neuroinflammatory response (Iba-1) across the whole hippocampus, and the addition of nicotine increases cell apoptosis across the whole hippocampus. HFD alone was not detrimental in our model, but in the presence of nicotine-free e-vapour, it differentially affected apoptosis, while the addition of nicotine increased nAChR subunits.

Depression is a clinically common and easily overlooked mental disease. Quercetin is a flavonoid compound, which has anti-inflammatory and antioxidant roles. Previous reports presented the anti-depressant role of quercetin. Nevertheless, the latent mechanism of the anti-depressant function of quercetin is blurry. This research aimed to probe its effects on corticosterone (CORT)-induced depression-like behaviors and explore the underlying mechanism. A depression model was established by subcutaneous injection of CORT (20 mg/kg). Thereafter, CORT-treated mice were given 40 mg/kg and 80 mg/kg of quercetin by gavage. This study found that quercetin mitigated depression-like behaviors, as evidenced by increased the number of line crossings, swimming time, and time spent in open arm and reduced thigmotaxis time in CORT-challenged mice in open field test and decreased immobility time as well as the swimming and climbing time in forced swim test and increased number of head dips, time spent and entries in open arm elevated plus maze test. Also, quercetin exerted anti-inflammatory and anti-oxidation effects in hippocampus and prefrontal cortex of CORT-induced mice. Additionally, quercetin alleviated the pathological injury of the liver tissue and weakened alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations of the serum in CORT-induced mice. Quercetin also suppressed Caspase-3 content but advanced vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) contents in hippocampus of CORT-treated mice. Based on these results, quercetin mitigated CORT-induced depression-like behaviors, and the mechanism was partly related to the repression of neuroinflammation and oxidative damage.