Melatonin attenuates affective disorders and cognitive deficits induced by perinatal exposure to a glyphosate-based herbicide via antioxidant pathway in adult male and female rats.

The massive use of herbicides, particularly glyphosate-based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4 mg/kg) from postnatal days 30-58. Our results show that GBH increases anxiety-like behavior levels in offspring, as well as depression-like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate-based pesticides. It will then be interesting to further our work to fully understand the sex-dependent effect of melatonin.

Exploring the neuroprotective role of melatonin against nickel-induced neurotoxicity in the left hippocampus.

Previous studies have demonstrated that the hippocampus, a crucial region for memory and cognitive functions, is particularly vulnerable to adverse effects of exposure to heavy metals. Nickel (Ni) is a neurotoxic agent that, primarily induces oxidative stress, a process known to contribute to cellular damage, which consequently affects neurological functions. The antioxidant properties of melatonin are a promising option for preventing the adverse effects of Ni, especially by protecting cells against oxidative stress and related damage. In our investigation of the potential neuroprotective effects of melatonin against Ni-induced neurotoxicity, we chose to administer melatonin through intraperitoneal injection in rats following an intrahippocampal injection of Ni into the left hippocampus. This approach allows us a targeted investigation into the influence of melatonin on the neurotoxic effects of Ni, particularly within the crucial context of the hippocampus. In the present study, we demonstrated that melatonin efficiency reduced lactate dehydrogenase level, and preserved antioxidant enzyme activities in Ni-exposed hippocampal tissue. It also mitigated the decline in superoxide dismutase and catalase activities. On the other hand, melatonin could act directly by reducing reactive oxygen species Ni-induced overproduction. Taking to gather these two potential mechanisms of action could be responsible for the adverse effect of Ni on the behavioral alteration observed in our study. This study provides significant insights into the potential of melatonin to mitigate the detrimental effects of Ni on the brain, particularly into the hippocampal region, suggesting its possible implications for the treatment of neurological disorders related to Ni exposure.

Subchronic Exposure to Mixture of Cadmium, Copper, and Nickel Induces Neurobehavioral Deficits and Hippocampal Oxidative Stress of Wistar Rats.

The present study was aimed at evaluating the influence of the subchronic exposure of cadmium (Cd), copper (Cu), and nickel (Ni) mixtures on affective behaviors, memory impairment, and oxidative stress (OS) in the hippocampus. Thirty male Wistar rats were divided into 5 equal groups. Group 1 (control) received a saline solution (NaCl 0.9%). Groups 2, 3, and 4 received Cd (0.25 mg/kg), Cu (0.5 mg/kg), and Ni (0.25 mg/kg), respectively, while group 5 received a Cd, Cu, and Ni mixture through intraperitoneal injections for 2 months. After the exposure period, all rats were submitted to behavioral tests. Subsequently, OS markers and histological changes in the rats' hippocampi were assessed. Results showed that a 2-month exposure to the mixtures of metals (MM) has led to higher anxiety-like and depression-like behaviors and cognitive deficits in rats when compared to the control group and the individual metals. Furthermore, the MM induced heightened OS, evidenced by the rise in lipid peroxidation and nitric oxide levels. These effects were accompanied by a decrease in superoxide dismutase and catalase activities in the hippocampus. The histopathological analysis also supported that MM caused a neuronal loss in the CA3 sub-region. Overall, this study underscores that subchronic exposure to the Cd, Cu, and Ni mixture induces an OS status and histological changes in the hippocampus, with important affective and cognitive behavior variations in rats.

Melatonin is a Neuroprotective and Antioxidant Agent against Neurotoxicity Induced by an Intrahippocampal Injection of Nickel in Rats.

The investigation into the hippocampal function and its response to heavy metal exposure is crucial for understanding the mechanisms underlying neurotoxicity, this can potentially inform strategies for mitigating the adverse effects associated with heavy metal exposure. Melatonin is an essential neuromodulator known for its efficacy as an antioxidant. In this study, we aimed to determine whether melatonin could protect against Nickel (Ni) neurotoxicity. To achieve this, we performed an intracerebral injection of Ni (300 µM NiCl2) into the right hippocampus of male Wistar rats, followed by melatonin treatment. Based on neurobehavioral and neurobiochemical assessments, our results demonstrate that melatonin efficiently enhances Ni-induced behavioral dysfunction and cognitive impairment. Specifically, melatonin treatment positively influences anxious behavior, significantly reduces immobility time in the forced swim test (FST), and improves learning and spatial memory abilities. Moreover, neurobiochemical assays revealed that melatonin treatment modulates the Ni-induced alterations in oxidative stress balance by increasing antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase (CAT). Additionally, we observed that melatonin significantly attenuated the increased levels of lipid peroxidation (LPO) and nitric oxide (NO). In conclusion, the data from this study suggests that melatonin attenuates oxidative stress, which is the primary mechanism responsible for Ni-induced neurotoxicity. Considering that the hippocampus is the main structure involved in the pathology associated with heavy metal intoxication, such as Ni, these findings underscore the potential therapeutic efficacy of melatonin in mitigating heavy metal-induced brain damage.

Melatonin modulates copper-induced anxiety-like, depression-like and memory impairments by acting on hippocampal oxidative stress in rat.

Copper (Cu) is a heavy metal with the ability to induce, at high levels, neurobehavioral alterations, and oxidative stress (OS). On the other hand, melatonin (Mel) is a neurohormone that protects neurons from OS and has a modulatory effect on several behavioral processes. The present experiment was aimed to examine the effect of Mel treatment on Cu-induced anxiety-like, depression-like behaviors, memory impairment, and OS in hippocampus. Herein, adult Wistar rats of both genders received daily Mel (4 mg/kg) thirty minutes before CuCl2 (1 mg/kg), by intraperitoneal injections for 8 weeks. After the administration period, all rats were submitted to the behavioral tests. Thereafter, OS parameters and histology of the hippocampus were evaluated. The results demonstrate that Mel treatment attenuated Cu-induced anxiety-like and depression-like behaviors, and it improved memory deficits Cu-treated rats. Furthermore, Mel attenuated Cu-provoked OS by reducing lipid peroxidation (LPO) and nitric oxide (NO) levels and enhancing superoxide dismutase (SOD) and catalase (CAT) activities in the hippocampus. The histopathological analysis also supported these results. In conclusion, these findings show that Mel treatment exerted neuroprotective effects against Cu-induced neurobehavioral changes which may be related to reduction of hippocampal OS. Besides, the effects of Cu and Mel were gender dependent, being more marked in females compared to male rats.

Melatonin Ameliorates Cadmium-Induced Affective and Cognitive Impairments and Hippocampal Oxidative Stress in Rat.

The present work aims to evaluate the effect of melatonin (Mel) on affective and cognitive disorders induced by chronic exposure to Cadmium (Cd). Male and female Wistar rats received either an intraperitoneal injection of saline solution NaCl (0.9%), Mel (4 mg/kg), Cd (1 mg/kg), or Cd (1 mg/kg) + Mel (4 mg/kg) for 8 weeks. Behavioral disorders were evaluated by different tests mainly the open field and elevated plus maze tests for anxiety-like behavior, forced swimming test (FST) for depression-like behavior, and the Y-maze and Morris water maze (MWM) tests for cognitive disorders. Thereafter, oxidative stress indices and histology of the hippocampus were evaluated. The results confirm that Cd administration has anxiogenic-like effects in both anxiety tests and depressive-like effects in the FST and leads to memory and learning disabilities in the Y-maze and MWM. We also report that Mel counteracts these neurobehavioral disorders. Biochemical assays showed that rats intoxicated with Cd significantly increased levels of nitric oxide (NO) and lipid peroxidation (LPO), while the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly decreased in the hippocampus. In contrast, Mel administration attenuates the Cd-induced changes. The histopathological studies in the hippocampus of rats also supported that Mel markedly reduced the Cd-induced neuronal loss in CA3 sub-region. Overall, our results suggest that Mel could be used to protect against Cd-induced neurobehavioral changes via its antioxidant properties in the hippocampus. The effects of Cd and Mel are sex-dependent, knowing that Cd is more harmful in males, while Mel is more protective in females.

Intrahippocampal Effects of Nickel Injection on the Affective and Cognitive Response in Wistar Rat: Potential Role of Oxidative Stress.

The present study focused on affective and cognitive behaviors in male Wistar rats, following direct and unique exposure to nickel chloride (NiCl2), as well as the possible involvement of oxidative stress. The rats were exposed to NiCl2 (300 µM), by intracerebral administration of 2 µL of this metal at the right hippocampus, using the stereotaxic approach. Five days after the surgery, a battery of behavioral tests was performed, including the open-field test (OFT) and elevated plus maze test (EPM) to assess the state of anxiety-like behavior and forced swimming test (FST) for depressive-like behavior. Y-maze and Morris Water Maze (MWM) were used to evaluate working memory and spatial learning. Thereafter, oxidative stress markers of the hippocampus were evaluated. The results confirm that NiCl2 exerts anxiogenic effects in both anxiety tests and depressogenic effects in the FST. In addition, MWM and Y-maze data show that NiCl2 causes memory and spatial learning disorders. The biochemical assay results showed that intrahippocampal injection of NiCl2 increased the levels of nitric oxide and lipid peroxidation (p < 0.001), while the activities of catalase and superoxide dismutase were significantly decreased in the hippocampus (p < 0.01). Overall, these results suggest that NiCl2 causes affective and cognitive disorders and oxidative stress in rats.

Chronic copper exposure leads to hippocampus oxidative stress and impaired learning and memory in male and female rats.

Environmental and occupational exposures to copper (Cu) play a pivotal role in the etiology of some neurological diseases and reduced cognitive functions. However, the precise mechanisms of its effects on cognitive function have not been yet thoroughly established. In our study, we aimed to investigate the behavior and neurochemical alterations in hippocampus of male and female rats, chronically exposed to copper chloride (CuCl2) and the possible involvement of oxidative stress. Twenty-four rats, for each gender, were divided into control and three test groups (n = 6), and were injected intraperitoneally with saline (0.9% NaCl) or CuCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After the treatment period, Y-maze test was used for the evaluation of spatial working memory and the Morris Water Maze (MWM) to test the spatial learning and memory. Biochemical determination of oxidative stress levels in hippocampus was performed. The main results of the present work are working memory impairment in spatial Y-maze which induced by higher Cu intake (1 mg/kg) in male and female rats. Also, In the MWM test, the spatial learning and memory were significantly impaired in rats treated with Cu at dose of 1 mg/kg. Additionally, markers of oxidative stress such as catalase, superoxide dismutase, lipid peroxidation products and nitric oxide levels were significantly altered following Cu treatments. These data propose that compromised behavior following Cu exposure is associated with increase in oxidative stress.

Neuroprotective effect of melatonin on nickel-induced affective and cognitive disorders and oxidative damage in rats.

The present work is carried out to explore the neuroprotective potential of Melatonin(Mel), on Ni-induced neurobehavioral, biochemical and histological alterations in male and female rats. The rats were intraperitoneally administered by nickel chloride (NiCl2, 1 mg/kg) and Mel (4 mg/kg) for 60 days. A neurobehavioral assessment was performed. Biochemical determinations of oxidative stress (OS) levels, and histological analysis of hippocampal tissues were also performed. Results showed that Nickel (Ni) treatment increased anxiety-like and depression-like behavior in rats. Besides, cognitive behavior on the Morris water maze was compromised following Ni treatment. Alongside this, Ni elevated hippocampal OS markers like lipid peroxidation and nitric oxide formation with a decrease in superoxide dismutase and catalase activities. Histological observations confirmed these results. Significantly, Mel administration alleviated neurobehavioral changes in Ni-treated rats of both genders. Also, Mel attenuated Ni-induced OS and increased the activities of antioxidant enzymes. The histopathological studies in the hippocampus supported that Mel markedly reduced the Ni-induced neuronal loss. In conclusion, this study suggests that Mel has a neuroprotective effect against Ni-induced neurobehavioral alterations, which may be related to lowering OS in the hippocampus.

Effect of Chronic Administration of Nickel on Affective and Cognitive Behavior in Male and Female Rats: Possible Implication of Oxidative Stress Pathway.

Nickel (Ni) toxicity has been reported to produce biochemical and behavioral dysfunction. The present study was undertaken to examine whether Ni chronic administration can induce alterations of affective and cognitive behavior and oxidative stress in male and female rats. Twenty-four rats, for each gender, divided into control and three test groups (n = 6), were injected intraperitoneally with saline (0.9% NaCl) or NiCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. The Morris Water Maze was used to evaluate the spatial learning and memory. The hippocampus of each animal was taken for biochemical examination. The results showed that Ni administration dose dependently increased anxiety-like behavior in both tests. A significant increase in depression-like symptoms was also exhibited by Ni treated rats. In the Morris Water Maze test, the spatial learning and memory were significantly impaired just in males treated with 1 mg/kg of Ni. With regard to biochemical analysis, activity of catalase (CAT) and superoxide dismutase (SOD) were significantly decreased, while the levels of nitric oxide (NO) and lipid peroxidation (LPO) in the hippocampus were significantly increased in the Ni-treated groups. Consequently, chronic Ni administration induced behavioral and biochemical dysfunctions.