Oxidative Stress In Cerebellum Research Articles

N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stress and inflammation may contribute to ASD-related behaviors is still poorly understood. Here, we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, an established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleens of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB and impaired the production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated Shank3b-/- animals. Taken together, our results provide clear evidence of the key role of cerebellar oxidative stress and inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder.

Lead induced cerebellar toxicology of developmental Japanese quail (Coturnix japonica) via oxidative stress-based Nrf2/Keap1 pathway inhibition and glutathione-mediated apoptosis signaling activation

Lead (Pb) is a heavy metal that has been recognized as a neurotoxin, meaning it can cause harmful effects on the nervous system. However, the neurotoxicology of Pb to birds still needs further study. In this study, we examined the neurotoxic effects of Pb exposure on avian cerebellum by using an animal model-Japanese quail (Coturnix japonica). The one-week old male chicks were exposed to 50, 200 and 500mg/kg Pb of environmental relevance in the feed for five weeks. The results showed Pb caused cerebellar microstructural damages charactered by deformation of neuroglia cells, granule cells and Purkinje cells with Nissl body changes. Moreover, cerebellar neurotransmission was disturbed by Pb with increasing acetylcholine (ACh) and decreasing acetylcholinesterase (AChE), dopamine (DA), γ-Aminobutyric Acid (GABA) and Na+/K+ ATPase. Meanwhile, cerebellar oxidative stress was caused by Pb exposure represented by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) as well as decreasing catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH) and superoxide dismutase (SOD). Moreover, RNA-Seq analysis showed that molecular signaling pathways in the cerebellum were disrupted by Pb exposure. In particular, the disruption of nuclear factor erythroid-2-related factor 2 (Nfr2)/kelch-like ECH-associated protein 1 (Keap1) pathway and glutathione metabolism pathway indicated increasing cell apoptosis and functional disorder in the cerebellum. The present study revealed that Pb induced cerebellar toxicology through structural injury, oxidative stress, neurotransmission interference and abnormal apoptosis.

Pomegranate Extract Administration Reverses Loss of Motor Coordination and Prevents Oxidative Stress in Cerebellum of Aging Mice.

The cerebellum is responsible for complex motor functions, like maintaining balance and stance, coordination of voluntary movements, motor learning, and cognitive tasks. During aging, most of these functions deteriorate, which results in falls and accidents. The aim of this work was to elucidate the effect of a standardized pomegranate extract during four months of supplementation in elderly mice to prevent frailty and improve the oxidative state. Male C57Bl/6J eighteen-month-old mice were evaluated for frailty using the "Valencia Score" at pre-supplementation and post-supplementation periods. We analyzed lipid peroxidation in the cerebellum and brain cortex and the glutathione redox status in peripheral blood. In addition, a set of aging-related genes in cerebellum and apoptosis biomarkers was measured via real-time polymerase chain reaction (RT-PCR). Our results showed that pomegranate extract supplementation improved the motor skills of C57Bl/6J aged mice in motor coordination, neuromuscular function, and monthly weight loss, but no changes in grip strength and endurance were found. Furthermore, pomegranate extract reversed the increase in malondialdehyde due to aging in the cerebellum and increased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the blood. Finally, aging and apoptosis biomarkers improved in aged mice supplemented with pomegranate extract in the cerebellum but not in the cerebral cortex.

Amelioration of neurobehavioral, biochemical, and morphological alterations associated with silver nanoparticles exposure by taurine in rats.

The adverse effect of silver nanoparticles (AgNPs) on the nervous system is an emerging concern of public interest globally. Taurine, an essential amino acid required for neurogenesis in the nervous system, is well-documented to possess antioxidant, anti-inflammatory, and antiapoptotic activities. Yet, there is no report in the literature on the effect of taurine on neurotoxicity related to AgNPs exposure. Here, we investigated the neurobehavioral and biochemical responses associated with coexposure to AgNPs (200 µg/kg body weight) and taurine (50 and 100 mg/kg body weight) in rats. Locomotor incompetence, motor deficits, and anxiogenic-like behavior induced by AgNPs were significantly alleviated by both doses of taurine. Taurine administration enhanced exploratory behavior typified by increased track plot densities with diminished heat maps intensity in AgNPs-treated rats. Biochemical data indicated that the reduction in cerebral and cerebellar acetylcholinesterase activity, antioxidant enzyme activities, and glutathione level by AgNPs treatment were markedly upturned by both doses of taurine. The significant abatement in cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, hydrogen peroxide, and lipid peroxidation was evident in rats cotreated with AgNPs and taurine. Further, taurine administration abated nitric oxide and tumor necrosis factor-alpha levels cum myeloperoxidase and caspase-3 activities in AgNPs-treated rats. Amelioration of AgNPs-induced neurotoxicity by taurine was confirmed by histochemical staining and histomorphometry. In conclusion, taurine via attenuation of oxido-inflammatory stress and caspase-3 activation protected against neurotoxicity induced by AgNPs in rats.

Neurobehavioral and biochemical responses to artemisinin-based drug and aflatoxin B1 co-exposure in rats.

Populations in malaria endemic areas are frequently exposed to mycotoxin-contaminated diets. The possible toxicological outcome of co-exposure to dietary aflatoxin B1 (AFB1) and artemisinin-based combination therapy warrants investigation to ascertain amplification or attenuation of cellular injury. Here, we investigated the neurobehavioral and biochemical responses associated with co-exposure to anti-malarial drug coartem, an artemether-lumefantrine combination (5mg/kg body weight, twice a day and 3days per week) and AFB1 (35 and 70µg/kg body weight) in rats. Motor deficits, locomotor incompetence, and anxiogenic-like behavior induced by low AFB1 dose were significantly (p < 0.05) assuaged by coartem but failed to rescue these behavioral abnormalities in high AFB1-dosed group. Coartem administration did not alter exploratory deficits typified by reduced track plot densities and greater heat map intensity in high AFB1-dosed animals. Furthermore, the reduction in cerebral and cerebellar acetylcholinesterase activity, anti-oxidant enzyme activities, and glutathione and thiol levels were markedly assuaged by coartem administration in low AFB1 group but not in high AFB1-dosed animals. The significant attenuation of cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, xanthine oxidase activity, and lipid peroxidation by coartem administration was evident in low AFB1 group but not high AFB1 dose. Although coartem administration abated nitric oxide level, activities of myeloperoxidase, caspase-9, and caspase-3 in animals exposed to both doses of AFB1, these indices were significantly higher than the control. Coartem administration ameliorated histopathological and mophometrical changes due to low AFB1 exposure but not in high AFB1 exposure. In conclusion, contrary to AFB1 alone, behavioral and biochemical responses were not altered in animals singly exposed to coartem. Co-exposure to coartem and AFB1 elicited no additional risk but partially lessened neurotoxicity associated with AFB1 exposure.

Preventive effect of quercetin-Loaded nanophytosome against autistic-like damage in maternal separation model: The possible role of Caspase-3, Bax/Bcl-2 and Nrf2

The autism is an abnormality in the neuronal advance which starts before age 3 recognized by defective behaviors. This study aimed to make quercetin-loaded nanophytosomes (QNP) on behavioral deficits, cerebellar oxidative stress and apoptosis in an autistic-like model caused by maternal separation (MS). The newborn rats are randomly categorized into seven groups, including control, positive control, disease, and diseases treated with quercetin (10 and 40mg/kg) and QNP (10 and 40mg/kg). Pups exposed to MS for 3h per day from postnatal days (PND) 1-9 showed behavioral impairment in adult rats compared to control group. The oral administration of quercetin and QNP was constantly started after the lactation period (21 postnatal days) for three weeks. Autistic-like behaviors, antioxidant parameters, and Nrf2, Bax/Bcl-2, and Caspase-3 expressions were surveyed in the cerebellum. Quercetin (40mg/kg) treated improved some behavioral disorders. Also, the improvement of oxidative stress parameters, Nrf2 and apoptotic factors gene expression was observed in the cerebellum of quercetin (40mg/kg) treated (p<0.01). QNP treatment (10 and 40mg/kg) significantly ameliorated anxiety-like behaviors, line crossing, and grooming index (p<0.001), lipid peroxidation (p<0.001), and increased catalase (CAT) (p<0.001), superoxide dismutase (SOD) (p<0.001), glutathione peroxidase (GPx) (p<0.001) activity, and glutathione (GSH) levels (p<0.05). Moreover, QNP significantly reduced Caspase-3 and Bax expression (p<0.001), but increased Bcl-2, and Nrf2 expressions (p<0.001). These findings indicated that QNP due to its high bioavailability was more effective than quercetin can be reduced autistic-like behavior, oxidative and apoptotic damages in the model of MS rats.

Calcium Supplementation Ameliorates Cerebellar Oxidative Stress in Lactational Aluminum-induced Neurotoxicity in Rats.

The neurotoxic effects of aluminum exposure during the critical period of neurodevelopment have been well documented. This study investigated the known protective effects of calcium supplementation on the cerebellum of juvenile Wistar rats following aluminum-induced neurotoxicity during lactation. Four groups of juvenile rats were exposed via lactation to distilled water (control group), aluminum (40 mg/kg/d), calcium supplement (50 mg/kg/d), and a combination of both aluminum and calcium from postnatal day 4 to day 28. The cerebella of the animals were excised to access the levels of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]), lipid peroxidation (malondialdehyde), histomorphological alterations (hematoxylin and eosin staining), Nissl profile (cresyl fast violet staining), and glial activation (glial fibrillary acidic protein immunohistochemistry). Lactational aluminum significantly decreased the activities of superoxide dismutase and glutathione peroxidase while exacerbating lipid peroxidation and reactive astrocyte in cerebellar lysates. Lactational calcium supplementation normalized the activities of SOD and GPx, thereby preventing excessive lipid peroxidation and glial activation. Despite no apparent changes in the general histology of the cerebellum, aluminum-induced chromatolysis changes in the Purkinje cell layer, which was counteracted by the antioxidant propensities of calcium supplementation. These findings support that calcium supplementation significantly protects the cerebellum against aluminum-induced oxidative stress, chromatolysis, and neuroinflammation.

Protective Role of Vitamin C Against Biochemical Enzymes Alterations Induced by Exposure of Allethrin Based Mosquito Coil Smoke on Cerebellum of Male Albino RatsAn Experimental Study

Introduction: Among synthetic pyrethroids allethrin is widely used as active ingredient in mosquito coils. Many experimental studies have proved that pyrethroids cause neurotoxicity and result into derangements of biochemical enzymes including oxidative stress markers and antioxidant levels in brain. Aim: To study alterations in biochemical markers (oxidative and antioxidant enzymes) in cerebellum of male albino Wistar rats induced by the exposure of allethrin based mosquito coil smoke along with protective role of withdrawal and exogenously administered vitamin C on these markers. Materials and Methods: This experimental study was conducted in the Department of Anatomy, King George's Medical University, Lucknow, Uttar Pradesh, India, during October 2014-September 2015. Total 42 male albino Wistar rats were divided into four groups. The first group contained 12 rats was used as control, group II with 12 rats was given 8 hours daily exposure of allethrin based mosquito coil smoke via whole body inhalation for 6 days in a week for a total of 12 weeks. Group III contained eight rats and was given exposure same as group II and were further kept for 8 weeks to see the withdrawal effect. Group IV with 10 rats was given same exposure as group II, along with oral administration of 20 mg/kg body weight vitamin C. After 12 weeks of exposure cerebellum was dissected and then sent for biochemical enzyme estimation. Rats in group III were dissected after 8 weeks post 12 weeks of exposure. Comparisons were made between groups by using one way Analysis of Variance (ANOVA). Results: The exposure Group II showed significant rise (p&lt;0.001) in level of oxidative stress marker enzyme Malondialdehyde (MDA) and significant (p&lt;0.001) reduction in activities of antioxidants Glutathione Peroxidase (GPO), reduced Glutathione (GSH), Superoxide Dismutase (SOD) and Catalase (CAT) in comparison to Group I, III and IV. In vitamin C administered group IV the above parameters were found to be less affected. Intergroup comparison of oxidative stress markers level showed significant intergroup difference between Group I, II, group II, III and group II, IV. Conclusion: Allethrin based mosquito coil smoke causes oxidative stress in cerebellum of albino Wistar rats and vitamin C has ameliorative effect on biochemical alterations induced by sub-chronic whole body exposure of mosquito coil smoke.

Ultra-Endurance Associated With Moderate Exercise in Rats Induces Cerebellar Oxidative Stress and Impairs Reactive GFAP Isoform Profile.

Ultra-endurance (UE) race has been associated with brain metabolic changes, but it is still unknown which regions are vulnerable. This study investigated whether high-volume training in rodents, even under moderate intensity, can induce cerebellar oxidative and inflammatory status. Forty-five adult rats were divided into six groups according to a training period, followed or not by an exhaustion test (ET) that simulated UE: control (C), control + ET (C-ET), moderate-volume (MV) training and MV-ET, high-volume training (HV) and HV-ET. The training period was 30 (MV) and 90 (HV) min/day, 5 times/week for 3 months as a continuous running on a treadmill at a maximum velocity of 12 m/min. After 24 h, the ET was performed at 50% maximum velocities up to the animals refused to run, and then serum lactate levels were evaluated. Serum and cerebellar homogenates were obtained 24 h after ET. Serum creatine kinase (CK), lactate dehydrogenase (LDH), and corticosterone levels were assessed. Lipid peroxidation (LP), nitric oxide (NO), Interleukin 1β (IL-1β), and GFAP proteins, reduced and oxidized glutathione (GSH and GSSG) levels, superoxide dismutase (SOD) and catalase (CAT) activities were quantified in the cerebellum. Serum lactate concentrations were lower in MV-ET (∼20%) and HV-ET (∼40%) compared to the C-ET group. CK and corticosterone levels were increased more than ∼ twofold by HV training compared to control. ET increased CK levels in MV-ET vs. MV group (P = 0.026). HV induced higher LP levels (∼40%), but an additive effect of ET was only seen in the MV-ET group (P = 0.02). SOD activity was higher in all trained groups vs. C and C-ET (P < 0.05). CAT activity, however, was intensified only in the MV group (P < 0.02). The 50 kDa GFAP levels were enhanced in C-ET and MV-ET vs. respective controls, while 42 kDa (∼40%) and 39 kDa (∼26%) isoform levels were reduced. In the HV-ET group, the 50 KDa isoform amount was reduced ∼40–60% compared to the other groups and the 39 KDa isoform, increased sevenfold. LDH levels, GSH/GSSG ratio, and NO production were not modified. ET elevated IL-1β levels in the CT and MV groups. Data shows that cerebellar resilience to oxidative damage may be maintained under moderate-volume training, but it is reduced by UE running. High-volume training per se provoked systemic metabolic changes, cerebellar lipid peroxidation, and unbalanced enzymatic antioxidant resource. UE after high-volume training modified the GFAP isoform profile suggesting impaired astrocyte reactivity in the cerebellum.

Locomotor mal-performance and gait adaptability deficits in sickle cell mice are associated with vascular and white matter abnormalities and oxidative stress in cerebellum

Patients with sickle cell disease (SCD) can develop strokes and as a result, present neurologic and neurocognitive deficits. However, recent studies show that even without detectable cerebral parenchymal abnormalities on imaging studies, SCD patients can have significant cognitive and motor dysfunction, which can present as early as during infancy. As the cerebellum plays a pivotal role in motor and non-motor functions including sensorimotor processing and learning, we examined cerebellar behavior in humanized SCD mice using the Erasmus ladder. Homozygous (sickling) mice had significant locomotor malperformance characterized by miscoordination and impaired locomotor gait/stepping pattern adaptability. Conversely, Townes homozygous mice had no overall deficits in motor learning, as they were able to associate a conditioning stimulus (high-pitch warning tone) with the presentation of an obstacle and learned to decrease steptimes thereby increasing speed to avoid it. While these animals had no cerebellar strokes, these locomotor and adaptive gait/stepping patterns deficits were associated with oxidative stress, as well as cerebellar vascular endothelial and white matter abnormalities and blood brain barrier disruption, suggestive of ischemic injury. Taken together, these observations suggest that motor and adaptive locomotor deficits in SCD mice mirror some of those described in SCD patients and that ischemic changes in white matter and vascular endothelium and oxidative stress are biologic correlates of those deficits. These findings point to the cerebellum as an area of the central nervous system that is vulnerable to vascular and white matter injury and support the use of SCD mice for studies of the underlying mechanisms of cerebellar dysfunction in SCD.

Evaluation of Varied Modalities of Tocotrienol Supplementations to Counter the Cerebellar Oxidative Stress Caused by Low-to-moderate Doses of Ethanol in Rats

Background and Objectives: Self-intoxication with Ethanol (Et) is a common problem worldwide. Being a psychoactive drug, neurotoxic effects of Et are well known. Cerebellum is highly vulnerable to Et exposure. Tocotrienols (T3) are relatively rare components of vitamin E and have the potential to prevent the oxidative stress and act as neuroprotective. Varied modalities of T3 supplementations were evaluated to identify the possibilities of countering cerebellar oxidative stress caused by low-to-moderate doses of Et exposure. Methods: Four phase of experiments were carried out with nil (Et-0) and three doses of Et exposures (Et-I, Et-II and Et-III) for 4 weeks. In each phase, 4 groups of Wistar rats were maintained with sham supplementation (NT3), Prior Supplementation (PT3), Simultaneous Supplementation (ST3) and Total Supplementation (TT3) with T3 for 6 weeks. Cerebellar levels of reduced Glutathione (GSH), Lipid Peroxidation (LPO) and activities of catalase, Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Glutathione Reductase (GR) were estimated and Superoxide and Peroxide Handling Capacities (SPHCs) were calculated. Results: All the tested cerebellar oxidative stress parameters and handling capacities were significantly influenced by the modalities of T3 supplementation. However, low-to-moderate doses of Et exposures contributed significantly in alterations of LPO level, GPx activity, GR activity and glutathione-dependent SPHC of cerebellum. Conclusion: Critical evaluation of studied parameters suggest insufficient overall performance of ST3 type of supplementation, whereas, TT3 type of supplementation was the best among the modalities of T3 supplementation. However, excess T3 supplementation may not be beneficial in some cases of oxidative stress parameters and SPHC of cerebellum.

Early Celastrol Administration Prevents Ketamine-Induced Psychotic-Like Behavioral Dysfunctions, Oxidative Stress and IL-10 Reduction in The Cerebellum of Adult Mice.

Administration of subanesthetic doses of ketamine during brain maturation represents a tool to mimic an early insult to the central nervous system (CNS). The cerebellum is a key player in psychosis pathogenesis, to which oxidative stress also contributes. Here, we investigated the impact of early celastrol administration on behavioral dysfunctions in adult mice that had received ketamine (30 mg/kg i.p.) at postnatal days (PNDs) 7, 9, and 11. Cerebellar levels of 8-hydroxydeoxyguanosine (8-OHdG), NADPH oxidase (NOX) 1 and NOX2, as well as of the calcium-binding protein parvalbumin (PV), were also assessed. Furthermore, celastrol effects on ketamine-induced alterations of proinflammatory (TNF-α, IL-6 and IL-1β) and anti-inflammatory (IL-10) cytokines in this brain region were evaluated. Early celastrol administration prevented ketamine-induced discrimination index decrease at adulthood. The same was found for locomotor activity elevations and increased close following and allogrooming, whereas no beneficial effects on sniffing impairment were detected. Ketamine increased 8-OHdG in the cerebellum of adult mice, which was also prevented by early celastrol injection. Cerebellar NOX1 levels were enhanced at adulthood following postnatal ketamine exposure. Celastrol per se induced NOX1 decrease in the cerebellum. This effect was more significant in animals that were early administered with ketamine. NOX2 levels did not change. Ketamine administration did not affect PV amount in the cerebellum. TNF-α levels were enhanced in ketamine-treated animals; however, this was not prevented by early celastrol administration. While no changes were observed for IL-6 and IL-1β levels, ketamine determined a reduction of cerebellar IL-10 expression, which was prevented by early celastrol treatment. Our results suggest that NOX inhibition during brain maturation prevents the development of psychotic-like behavioral dysfunctions, as well as the increased cerebellar oxidative stress and the reduction of IL-10 in the same brain region following ketamine exposure in postnatal life. This opens novel neuroprotective opportunities against early detrimental insults occurring during brain development.

Cynodon dactylon extract ameliorates cognitive functions and cerebellar oxidative stress in whole body irradiated mice

Objective: To explore the effect of hydroalcoholic extract of Cynodon dactylon on the whole body radiation-induced oxidative status of the cerebellum and cognitive impairments in mice.Methods: Swiss albino mice were randomly divided into the control group, radiation control group, low dose and high dose Cynodon dactylon extract treated groups and pre-treated with Cynodon dactylon extract before irradiation. Cynodon dactylon extract was administered for 7 d daily in low dose (0.25 g/kg) and high dose (1 g/kg). On day 7, mice were irradiated with a sublethal dose of 5 Gy gamma rays. Motor coordination was assessed by elevated rotarod test and spatial memory was studied by water maze test. Subsequently, biochemical markers (glutathione, lipid peroxidation and nitric oxide levels) in the cerebellum were evaluated.Results: The gamma irradiated group showed significant impairment in motor coordination and spatial memory compared to normal mice. Mice treated by Cynodon dactylon extract prior to gamma radiation showed good improvement in both paradigms compared to the radiation control group. Moreover, glutathione level was increased, while lipid peroxidation and nitric oxide levels were significantly reduced in mice receiving low dose and high dose of Cynodon dactylon extract compared to the radiation control group.Conclusions: The present study suggests the neuroprotective role of Cynodon dactylon against radiation-induced cognitive impairment and oxidative stress on the cerebellum of mice.

Postnatal Administration of Homocysteine Induces Cerebellar Damage in Rats: Protective Effect of Folic Acid

A widely held view suggests that homocysteine (Hcy) can contribute to neurodegeneration through promotion of oxidative stress. There is evidence that homocysteine is toxic to cerebellar Purkinje neurons in vitro; however, in vivo action of Hcy on Purkinje cell has not been investigated so far. Thus, this study was designed to evaluate the Hcy effects on neonatal rat cerebellum and cerebellar oxidative stress. We also evaluated the folic acid effects on biochemical alterations elicited by hyperhomocysteinemia (hHcy) in the cerebellum. Group I received normal saline, group II received Hcy subcutaneously twice a day at 8-h intervals (0.3-0.6μmol/g body weight), group III received Hcy + folic acid (0.011μmol/g body weight), and group IV received folic acid on postnatal day (PD) 4 until 25. On day 25, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in the cerebellum and motor cortex were assayed. Malondialdehyde (MDA) levels were also evaluated as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed in PD 25-27. Our results indicated that administration of Hcy increased plasma, cortical, and cerebellar total Hcy levels; reduced GPx activity; and induced lipid peroxidation in the cerebellum. Hcy impaired performance on the rotarod in rats. However, treatment with folic acid significantly attenuated motor coordination impairment, GPx activity reduction, the lipid peroxidation process, and significantly reduced plasma total Hcy levels. Histological analysis indicated that Hcy could decrease Purkinje cell count and folic acid prevented this toxic effect. We conclude that Hcy can induce neurotoxicity and folic acid has neuroprotective effects against cerebellar Hcy toxicity.

Morphological and Biochemical Features of Cerebellar Cortex After Exposure to Zinc Oxide Nanoparticles: Possible Protective Role of Curcumin.

Zinc oxide nanoparticles (ZnONPs) are widely used in the last decades. Therefore, investigation of its neurotoxic effect is important. This work aimed to investigate the potential adverse effects of ZnONPs on rat's cerebellar cortex and the possible neuroprotective role of curcumin (Cur). Forty male albino rats were randomly divided into four equal groups. Two groups were injected with ZnONPs and one group was previously received Cur before ZnONPs. At the end of the experiment, cerebellar tissue samples were prepared for histological, morphometric, immunohistochemical study, and tissue levels of oxidative stress markers and cytokine analysis. cerebellar damage is clearly visible with ZnONPs. Degeneration, loss, disorganization of cerebellar neurons was observed. Histopathological degeneration of Purkinje and granular cells together with loss of Nissl substance, astrocyte gliosis, and affection of cerebellar blood brain barrier were detected. Moreover, an apoptotic marker (caspase-3) was significantly expressed in Purkinje and granular layers together with elevated gene expression of P53 and COX-2 in cerebellar tissue of ZnONPs intoxicated group. Astrocyte gliosis and inflammatory markers IL-1, IL-6, and TNF-α were expressed significantly in ZnONPs intoxicated cerebellum. These changes were associated with evidence of cerebellar oxidative stress. Strikingly, treatment with Cur together with ZnONPs recorded morphological improvement, with increased number of Purkinje cells and decreased caspase +ve cells. These findings were confirmed by morphometric and statistical analysis. Cur ameliorates the deterious effect of ZnONPs on the cerebellar cortex through its antioxidant, antiapoptotic, and anti-inflammatory efficacies. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Cerebellar oxidative stress and fine motor impairment in adolescent rats exposed to hyperthermia-induced seizures is prevented by maternal caffeine intake during gestation and lactation

Febrile seizures (FS) is one of the most common convulsive disorders in infants and young children that only occurs during the first years of life in humans, when the cerebellum is still developing. Several works have shown that maternal caffeine consumption during gestation and lactation can exert protective effects on developing brain under pathological conditions. Here, we have used an animal model of FS to know whether maternal caffeine consumption during gestation and lactation exhibited protective effects on rat cerebellum. Pregnant rats were allowed to freely drink water or caffeine (1 g/l) during gestation and lactation. At PD13, neonates were submitted to hyperthermia-induced seizures (HIS) whereas pups not subject to hyperthermic stimulus were used as controls. 48 h, 5 and 20 days after HIS, rats were killed and plasma membranes and cytosolic fractions were isolated from cerebella. The enzymatic activities of glutathione reductase, glutathione S-transferase, caspase-3, 5´-nucleotidase and the levels of thiobarbituric acid reacting substances, adenosine A1 and A2A receptors were studied in these preparations. Furthermore, rats were tested in balance beam test and footprint test 20 days after HIS (PD33) in order to investigate the effect on fine motor coordination and gait patterns. Results obtained suggest that maternal caffeine consumption during gestation and lactation exerts two kinds of beneficial effects on cerebellum from rats submitted to HIS: a) at short term, maternal caffeine abolishes hyperthermic seizures induced-oxidative stress and caspase-3 activation and b) in adolescent rats (PD33), maternal caffeine prevents fine motor coordination impairment and gait disturbances.

Neuroprotective effect of mucuna pruriens seed extract on methyl mercury-induced oxidative stress in cerebellum of rats

Neuroprotective effect of mucuna pruriens seed extract on methyl mercury-induced oxidative stress in cerebellum of rats

Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain.

Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5mg/kg b.w. for 21days. Experimental rats were given MeHg and also administered with POEE (4mg/kg, orally) 1h prior to the administration of MeHg for 21days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity.

Chronic retinyl palmitate supplementation to middle-aged Wistar rats disrupts the brain redox homeostasis and induces changes in emotional behavior.

Aging process makes older adults especially vulnerable to neurodegeneration and mental disorders. Overconsumption-related neurotoxic effects of certain dietary nutrients by older population could represent a contribution factor for the development of neuropsychiatric conditions by this subpopulation. Thus, we here investigated whether chronic supplementation with retinyl palmitate, at doses commonly found in vitamin supplements (300, 600, and 3000 mcg of RAE/kg/day), could have an impact on emotional behavior of middle-aged Wistar rats. We report that supplementation with retinyl palmitate for 28 days induces an altered emotional state of middle-aged Wistar rats and oxidative stress in cerebellum, cerebral cortex, hippocampus, and striatum, associated with imbalance of enzymatic antioxidant defenses, decrease in non-enzymatic antioxidant defenses, and increase in protein and lipid damages. Our data show evidence for (i) changes in emotional reactivity, similar to anxiety, in middle-aged rats chronically supplemented with retinyl palmitate; and (ii) suggest a possible interrelation between pro-oxidant events in the brain and these differences in the behavioral profile that cannot be attributed to hepatotoxicity. Our results invite for additional studies to further investigate such interrelation.

Ameliorative effects of ferulic Acid against lead acetate-induced oxidative stress, mitochondrial dysfunctions and toxicity in prepubertal rat brain.

Epidemiological evidence has shown higher susceptibility of Children to the adverse effects of lead (Pb) exposure. However, experimental studies on Pb-induced neurotoxicity in prepubertal (PP) rats are limited. The present study aimed to examine the propensity of ferulic acid (FA), a commonly occurring phenolic acid in staple foods (fruits, vegetables, cereals, coffee etc.) to abrogate Pb-induced toxicity. Initially, we characterized Pb-induced adverse effects among PP rats exposed to Pb acetate (1,000-3,000ppm in drinking water) for 5weeks in terms of locomotor phenotype, activity of 5-aminolevulinic acid dehydratase (ALAD) in the blood, blood Pb levels and oxidative stress in brain regions. Further, the ameliorative effects of oral supplements of FA (25mg/kg bw/day) were investigated in PP rats exposed to Pb (3,000ppm). Pb intoxication increased the locomotor activity and FA supplements partially reversed the phenotype, while the reduced ALAD activity was also restored. FA significantly abrogated the enhanced oxidative stress in cerebellum (Cb) and hippocampus (Hc) as evidenced in terms of ROS generation, lipid peroxidation and protein carbonyls. Further, Pb-mediated perturbations in the glutathione levels and activity of enzymic antioxidants were also markedly restored. Furthermore, the protective effect of FA was discernible in striatum in terms of reduced oxidative stress, restored cholinergic activity and dopamine levels. Interestingly, reduced activity levels of mitochondrial complex I in Cb and enhanced levels in Hc among Pb-intoxicated rats were ameliorated by FA supplements. FA also decreased the number of damaged cells in cornu ammonis area CA1 and dentate gyrus as reflected by the histoarchitecture of Hc among Pb intoxicated rats. Collectively, our findings in the PP model allow us to hypothesize that ingestion of common phenolics such as FA may significantly alleviate the neurotoxic effects of Pb which may be largely attributed to its ability to abrogate oxidative stress.