Neurobehavioral Activity Research Articles

AMELIORATION OF ALUMINUM- AND FLUORIDE-INDUCED BEHAVIORAL ALTERATIONS THROUGH RESVERATROL IN RATS.

Objective: The objective of the study was to investigate the ameliorative effects of resveratrol against aluminum- and fluoride-altered neurobehavioral activities.Methods: Aluminum chloride (100 mg/kg body weight [bw])+sodium fluoride (10 mg/kg bw), aluminum chloride (100 mg/kg bw) + sodium fluoride (10 mg/kg bw) + resveratrol (30 mg/kg bw), and resveratrol (30 mg/kg bw) alone were given orally to II, III, and IV groups, respectively, and Group-I was served as control for 8 weeks. The bw, brain weight, grip strength, learning ability, and behavioral activities were assayed.Results: The results showed significantly (*p<0.05) altered body and brain weights, learning ability, grip strength, and behavioral activities in Group- II, whereas significant (*p<0.05) reversal was observed in Group-III.Conclusion: Taken together, the above findings conclude that resveratrol ameliorated aluminum and fluoride-altered neurobehavioral activities.

AMELIORATION OF ALUMINUM- AND FLUORIDE-INDUCED BEHAVIORAL ALTERATIONS THROUGH RESVERATROL IN RATS.

Objective: The objective of the study was to investigate the ameliorative effects of resveratrol against aluminum- and fluoride-altered neurobehavioral activities.Methods: Aluminum chloride (100 mg/kg body weight [bw])+sodium fluoride (10 mg/kg bw), aluminum chloride (100 mg/kg bw) + sodium fluoride (10 mg/kg bw) + resveratrol (30 mg/kg bw), and resveratrol (30 mg/kg bw) alone were given orally to II, III, and IV groups, respectively, and Group-I was served as control for 8 weeks. The bw, brain weight, grip strength, learning ability, and behavioral activities were assayed.Results: The results showed significantly (*p<0.05) altered body and brain weights, learning ability, grip strength, and behavioral activities in Group- II, whereas significant (*p<0.05) reversal was observed in Group-III.Conclusion: Taken together, the above findings conclude that resveratrol ameliorated aluminum and fluoride-altered neurobehavioral activities.

Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer’s disease

Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. There is evidence that brain tissue in patients with AD is exposed to oxidative stress during the course of the disease. Hesperetin (Hst) is a natural flavonoid, which has been reported to exert various biological activities such as antioxidant and anti-inflammatory effect. The present study aimed to investigate the effects of hesperetin and nano-hesperetin on neurobehavioral activity and superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx) and catalase (CAT) enzymes activity, malondialdehyde (MDA) and glutathione (GSH) levels in hippocampal area of rats in an experimental model of AD. The AD was induced in animals by intracerebroventricular injection of STZ (icv-STZ) unilaterally. Animals were treated with the Hst and nano-Hst (10, 20 mg/kg body weight), then after three successive weeks, recognition memory was examined (passive avoidance test and novel object recognition test) and antioxidant parameters were evaluated. In our study behavioral testes showed improvement on memory retrieval and recognition memory consolidation. Furthermore the Hst and nano-Hst increased the activity of antioxidant enzymes (SOD, glutathione GPx, GRx and CAT) and GSH levels and decreased MDA in the hippocampal area. These results suggested that Hst and nano-Hst may inhibit STZ-induced oxidative stress, and that it may possess therapeutic potential for the treatment of AD.

The effects of betulinic acid on neurobehavioral activity, electrophysiology and histological changes in an animal model of the Alzheimer’s disease

Alzheimer's disease (AD) is a common disorder characterized by aggregation and conversion of amyloid beta (Aβ) monomers to fibrils. Betulinic acid (BA) strongly accelerated this pathway through circumventing the oligomeric intermediate state. BA at doses of 0.2 and 0.4μM/10μl/rat (intra-hippocampal or i.h injection, vehicle: DMSO) was bilaterally administrated 180 and 10min before co-administration of Aβ (0.1μM/5μl/rat, i.h injection, vehicle: PBS) and Streptozotocin (STZ, 1.5mg/kg/10μl/rat, intracerebroventricular or i.c.v. injection, vehicle: aCSF). The behavioral assessments (spatial and passive avoidance memory, anxiety, locomotion, depression, and motor coordination), electrophysiological evaluations (hippocampal long- term potentiation (LTP)) as well as histological changes were evaluated 30days after injections. The indices of spatial and passive avoidance memory, anxiety/depression and LTP records were significantly impaired in AD rats in comparison with the sham. Pretreatment of BA (0.4μM) showed a more significant effect on memory, anxiety, all LTP parameters, and histological damage compared to a low dose in contrast to the AD group. Overall, BA pretreatment was able to prevent AD-induced neurobehavioral and LTP deficits in rats and the best effect was observed in molar ratio of 1:4 (Aβ to BA).

Effects of Beta-Adrenergic Blockade on Diabetes-Induced Neurobehavioral Alterations in Mice

Neurobehavioral activities were estimated in three groups of male albino mice using the open field, elevated plus maze, light/dark board, and hole-board tests. The control group included intact animals, while alloxan-induced diabetes was evoked in the other two groups (single i.p. injection of 120 mg/kg alloxan). In the third group, a nonspecific beta-adrenoreceptor antagonist, propranolol, was i.p. injected (40 mg/kg) before the induction of diabetes. In diabetic mice, all neurobehavioral indices tested in the four above-mentioned tests were significantly (P< 0.05) smaller than those in the control group. The frequencies of rearings and grooming episodes in the open field, number of entries into the open arms and time spent in these arms in the elevated plus maze test, and number of head dips in the hole-board test demonstrated the most intense drops (more than twofold). Pretreatment with propranolol provided significant (P < 0.05) normalization of all neurobehavioral indices in diabetic mice; such normalization with respect to the locomotion intensity, frequency of grooming, time spent in the open arms, and both indices in the light/dark board was nearly complete. Thus, diabetes in the animal model used is accompanied by the development of the state of abnormally high anxiety. The activity of the betaadrenergic system is noticeably involved in the formation of this state; pharmacological blocking of beta-adrenoreceptors provides significant anxiolytic effects.

Omega-3 fatty acid attenuates oxidative stress in cerebral cortex, cerebellum, and hippocampus tissue and improves neurobehavioral activity in chronic lead-induced neurotoxicity

Objectives: In view of the increasing risk of lead on human health, the present study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid on chronic lead-induced neurotoxicity and behavioral impairment in rats.Methods: Different neurobehavioral parameters, biochemical assays, and histopathological analyses in brain regions of rats were conducted.Results: Rats exposed to different doses of lead (lead acetate 2.5, 5.0, 7.5 mg/kg body weight p.o. for 90 days) caused a significant decrease in body weight, brain weight, and behavioral changes as compared to controls. Abnormal histopathological and increased levels of lead in blood and brain regions increased the levels of ROS, LPO, PCC and decreased the levels of GSH with concomitant reduction in SOD, CAT, and GPx activities in the brain region of rats treated with different doses of lead as compared to controls. Co-treatment of lead with omega-3 fatty acid (500 mg/kg body weight p.o. for 90 days) decreased the levels of ROS, LPO, PCC, and increased the level of GSH, also increased SOD, CAT, and GPx activity and showed improvements in behavioral as well as histopathological changes as compared to lead-treated groups.Discussion: Our results proved that omega-3 fatty acid improved behavioral deficits, altered histopathological and oxidative stress in lead-intoxicated rats. Among three different doses, 2.5 mg/kg b.wt. of lead along with omega-3 fatty acid was the most preventive dose for the neurotoxicity. This work reveals the potential of omega-fatty acid as a protective drug for lead neurotoxicity.

Rosuvastatin ameliorates cognitive impairment in rats fed with high-salt and cholesterol diet via inhibiting acetylcholinesterase activity and amyloid beta peptide aggregation.

Amyloid beta (Aβ) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aβ1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ1-42 aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aβ1-42 peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aβ1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.

HSP90 and pCREB alterations are linked to mancozeb-dependent behavioral and neurodegenerative effects in a marine teleost

The pesticide mancozeb (mz) is recognized as a potent inducer of oxidative stress due to its ability to catalyze the production of reactive oxygen species plus inhibiting mitochondrial respiration thus becoming an environmental risk for neurodegenerative diseases. Despite numerous toxicological studies on mz have been directed to mammals, attention on marine fish is still lacking. Thus, it was our intention to evaluate neurobehavioral activities of ornate wrasses (Thalassoma pavo) exposed to 0.2mg/l of mz after a preliminary screening test (0.07–0.3mg/l). Treated fish exhibited an evident (p<0.001) latency to reach T-maze arms (>1000%) while exploratory attitudes (total arm entries) diminished (−50%; p<0.05) versus controls during spontaneous exploration tests. Moreover, they showed evident enhancements (+111%) of immobility in the cylinder test. Contextually, strong (−88%; p<0.01) reductions of permanence in light zone of the Light/Dark apparatus along with diminished crossings (−65%) were also detected. Conversely, wrasses displayed evident enhancements (160%) of risk assessment consisting of fast entries in the dark side of this apparatus. From a molecular point of view, a notable activation (p<0.005) of the brain transcription factor pCREB occurred during mz-exposure. Similarly, in situ hybridization supplied increased HSP90 mRNAs in most brain areas such as the lateral part of the dorsal telencephalon (Dl; +68%) and valvula of the cerebellum (VCe; +35%) that also revealed evident argyrophilic signals. Overall, these first indications suggest a possible protective role of the early biomarkers pCREB and HSP90 against fish toxicity.

Cyclooxygenase-2 Directs Microglial Activation-Mediated Inflammation and Oxidative Stress Leading to Intrinsic Apoptosis in Zn-Induced Parkinsonism.

Inflammation is decisive in zinc (Zn)-induced nigrostriatal dopaminergic neurodegeneration; however, the contribution of cyclooxygenase-2 (COX-2) is not yet known. The present study aimed to explore the role of COX-2 in Zn-induced Parkinsonism and its association with the microglial activation. Male Wistar rats were treated intraperitoneally (i.p.) with Zn as zinc sulphate (20mg/kg) along with respective controls for 2-12weeks. In a few sets, animals were also treated with/without celecoxcib (CXB, 20mg/kg, i.p.), a selective COX-2 inhibitor. Indexes of the nigrostriatal neurodegeneration, oxidative stress, inflammation and apoptosis were measured in the animals/nigrostriatal tissue. Zn induced time-dependent increase in the expression of COX-2 while COX-1 expression was unaltered. Zn reduced the neurobehavioral activities, striatal dopamine content, tyrosine hydroxylase (TH) expression and number of dopaminergic neurons. While oxidative stress; microglial activation; expression of microglial cell surface marker-CD11b; cytochrome c release; caspase-9/3 activation; level of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 and Bcl-2-associated protein x (Bax) translocation from the cytosol to mitochondria were induced in the Zn-treated group, expression of B-cell lymphoma-2 (Bcl-2) was found to be reduced. CXB significantly attenuated Zn-induced increase in COX-2 expression and restored TH-expression, dopamine content, level of inflammatory cytokines and neurobehavioral indexes towards normalcy. Moreover, CXB also attenuated Zn-induced increase in microglial activation, oxidative stress and apoptotic markers towards normal levels. Results of the study thus demonstrate that COX-2 induces microglial activation that provokes the release of inflammatory mediators, which in turn augments oxidative stress and intrinsic apoptosis leading to dopaminergic neurodegeneration in Zn-induced Parkinsonism.

Neuregulin1β Effects on Brain Tissue via ERK5-Dependent MAPK Pathway in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

Neuregulin1β (NRG1β), a member of the excitomotor of tyrosine kinase receptor (erbB) family, was recently shown to play a neuroprotective role in cerebral ischemia-reperfusion injury. The present study analyzed the effects and its possible signaling pathway of NRG1β on brain tissues after cerebral ischemia-reperfusion injury. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion, followed by an NRG1β injection via the internal carotid artery. NRG1β injection resulted in significantly improved neurobehavioral activity according to the modified neurological severity score test. Tetrazolium chloridestaining revealed a smaller cerebral infarction volume; hematoxylin-eosin staining and transmission electron microscopy showed significantly alleviated neurodegeneration in the middle cerebral artery occlusion rats. Moreover, expression of phosphorylated MEK5, phosphorylated ERK5, and phosphorylated MEK2C increased after NRG1β treatment, and the neuroprotective effect of NRG1β was attenuated by an injection of the MEK5 inhibitor, BIX02189. Results from the present study demonstrate that NRG1β provides neuroprotection following cerebral ischemia-reperfusion injury via the ERK5-dependent MAPK pathway.

Neurobehavioural Changes in a Hemiparkinsonian Rat Model Induced by Rotenone.

Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study. To assess all the motor deficits in lesioned animals that are due to the depletion of dopaminergic neurons or its terminals, the lesioned animals were administered with anti-parkinsonian drug, Levodopa which should counteract motor deficits in rats. The unilateral partially lesioned PD model was induced by rotenone stereotaxically into two sites of striatum of male Wistar albino rats at a dosage of 25 μg of rotenone/site. Rats were tested for its neurobehavioural activity on 7th day, 14th day, 21st day and on 30th day after rotenone infusion and compared with the sham group and sacrificed on 21st and 30th day for microscopic studies. L-DOPA was administered from 21st day to 30th day after lesion and compared with the lesioned group for the motor performance and sacrificed on 30th day for histology. Statistical analysis using One-way Analysis of variance followed by Tukey's test was applied for behavioural studies. Statistical analysis showed that the signs and symptoms like motor in-coordination and postural disturbances are highly significant (p<0.05) on 14th and 21st day after administration of rotenone when compared to sham group. In L-DOPA treated rats, all the motor deficits were reversed. The neuronal cell death was minimal and sprouting of nerve terminals was detected. In lesioned group, the degeneration of nerve terminals and striatal neurons were in progressive manner. These findings suggest that intrastriatal infusion of rotenone at a moderate dose could be used for producing hemiparkinsonian partially lesioned animal model without any mortality. Hence, this model is suitable for evaluating behavioural studies and in drug screening programs even for a long term study.

ALTERATION OF NEUROBEHAVIOURAL ACTIVITIES BY CARBAMAZEPINE, PHENYTOIN AND THEIR COMBINATION IN WISTAR RATS: A MINI REVIEW

Antiepileptic drugs (AEDs) have been used for centuries in the treatment of seizures in both humans and animals. There are different varieties of AEDs to choose from, the choice of an AED is determined by the seizure type, effectiveness of the drug in controlling seizure, cost and the side effects of the drug used. Epilepsy therapy could be monotherapy, that is, the use of an appropriate AED or polytherapy in which case, two AEDs are combined particularly in the case of refractory epilepsy. The side effects of AEDs are diverse and affect virtually all the systems of the body. This review is aimed at studying the side effects associated with the administration of carbamazepine, phenytoin and their combination on learning, memory, locomotion and rearing activities in Wistar rats. Generally, the side effects of AEDs observed are not so detrimental because the discontinuation of the drugs usually cause a reverse of the effects observed. For this review, available informations on the effects of antiepileptic drugs on neurobehavioural activities were accessed from electronic databases.

Effects of different vehicles used in preclinical studies on the neurobehavioral profile and general activity of Sprague Dawley rats

Effects of different vehicles used in preclinical studies on the neurobehavioral profile and general activity of Sprague Dawley rats

The Anti-inflammatory Effects of Agmatine on Transient Focal Cerebral Ischemia in Diabetic Rats.

In the previous study, we observed agmatine (AGM) posttreatment immediately after 30 minutes of suture occlusion of the middle cerebral artery (MCAO) reduced the infarct size and neurological deficit in diabetic rats. The aim of the present study was to investigate the anti-inflammatory effect of AGM to reduce cerebral ischemic damage in diabetic rats. Normoglycemic (n=20) and streptozotocin-induced diabetic rats (n=40) were subjected to 30 minutes of MCAO followed by reperfusion. Twenty diabetic rats were treated with AGM (100 mg/kg, intraperitoneal) immediately after 30 minutes of MCAO. Modified neurological examinations and rotarod exercises were performed to evaluate motor function. Western blot and immunohistochemical analysis were performed to determine the expression of inflammatory cytokines in ischemic brain tissue. Real-time polymerase chain reaction was performed to measure the mRNA expression of high-mobility group box 1, receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4 RESULTS AND CONCLUSIONS:: AGM posttreatment improved the neurobehavioral activity and motor function of diabetic MCAO rats at 24 and 72 hours after reperfusion. Immunohistochemical analysis showed that AGM treatment significantly decreased the expression of inflammatory cytokines in diabetic MCAO rats at 24 and 72 hours after reperfusion (P<0.01). Western blotting and real-time polymerase chain reaction results indicated that AGM treatment significantly decreased the expression of high-mobility group box 1, RAGE, TLR2, and TLR4 in diabetic rats at 24 hours after reperfusion (P<0.05). This neuroprotective effect of AGM after MCAO was associated with modulation of the postischemic neuronal inflammation cascade.

Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia

ObjectiveRutin, a potent antioxidant, has been reported to reduce the risk of ischemic disease. Our study aims to prepare rutin-encapsulated-chitosan nanoparticles (RUT-CS-NPs) via ionic gelation method and determine its results, based on different parameters i.e. surface morphology characterization, in-vitro or ex-vivo release, dynamic light scattering and differential scanning calorimetry (DSC), for treating cerebral ischemia. MethodsUPLC-ESI-Q-TOF-MS/MS was used to evaluate the optimized RT-CS-NPs1 for brain-drug uptake as well as to follow-up the pharmacokinetics, bio-distrbution, brain-targeting efficiency and potential after intranasal administration (i.n.). Key findingsA particle size of <100nm for the formulation, significantly affected by drug:CS ratio, and entrapment efficiency and loading capacity of 84.98%±4.18% and 39.48%±3.16%, respectively were observed for RUT. Pharmacokinetics, bio-distribution, brain-targeting efficiency (1443.48±39.39%) and brain drug-targeting potential (93.00±5.69%) showed enhanced bioavailability for RUT in brain as compared to intravenous administration. In addition; improved neurobehavioral activity, histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO) induced cerebral ischemic rats model after i.n. administration of RUT-CS-NPs. ConclusionA significant role of mucoadhesive-RT-CS-NPs1 as observed after high targeting potential and efficiency of the formulation prove; RUT-CS-NPs are more effectively accessed and target easily the brain.

Quantification and evaluation of thymoquinone loaded mucoadhesive nanoemulsion for treatment of cerebral ischemia

Stroke is an important cause of deaths worldwide, resulting in an irreversible deterioration of the central nervous system. Finally, production of more free radicals. Therefore, Thymoquinone is having antioxidant property and reported to have a potential role in the amelioration of cerebral ischemia but due to low solubility and poor absorption; they exhibit low serum and tissue levels. Present work aims to prepare nanoemulsions in order enhance the bioavailability of drug and hence evaluate the drug targeting in brain via non-invasive nasal route administration. Thymoquinone Mucoadhesive Nanoemulsion (TMNE) was prepared by ionic gelation method; characterized for particles size, entrapment efficiency, zeta potential, and ex vivo permeation study. Optimized TMNE ended up with a mean globule size 94.8±6.61nm; zeta potential −13.5±1.01mV; drug content 99.86±0.35% and viscosity 110±12cp. Ultra Performance Liquid Chromatography-Photodiode Array (UPLC-PDA) based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (628.5786±44.79%) and brain drug-targeting potential (89.97±2.94%) studies via post intranasal administration which revealed enhanced bioavailability of TQ in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of TMNE.

Quality control analysis of Khamira Abresham Hakim Arshad Wala and Khamira Marwareed

Background: Unani system of medicine is based on the principles proposed by Galen, a Greek practitioner. Since then, many Arab and Persian scholars have contributed to the system. Among them, Ibn-e-Sina, an Arab philosopher and Physicist, who wrote “Kitab-al-shifa” are worth mentioning. This system has an extensive and inspiring record in India. Khamira Abresham Hakim Arshad Wala (KAHAW) and Khamira Marwareed (KM) are semisolid sugar-based preparations with potent cardiac tonic and well-known antioxidant properties. It has been studied that therapeutic intervention of KAHAW may be used to prevent or to decrease the deterioration of cognitive function and neurobehavioral activities, often associated with the generation of a free radical. However, no considerable attempt has been made for quality evaluation of KAHAW. Materials and Methods: In the present investigations, KAHAW and KM were evaluated for their phytochemical screening, physicochemical standards, presence of minerals, contaminants such as aflatoxins, pesticide residues, thin layer chromatography, and high performance thin layer chromatography (HPTLC) as per WHO and AYUSH guidelines for development of quality standards, which can be used by Unani industries. Results: Physicochemical parameters of the prepared compound formulation KAHAW and KM were studied such as total ash, acid insoluble ash, water soluble ash, solubility matter in alcohol and water, and loss on drying at 105°C, pH as per the methods described in WHO guidelines. The heavy metal, aflatoxins, and pesticide residues were also determined for safety evaluation. The total phenolic and flavonoid contents were estimated using catechin and quercetin as standard after preparing calibration plot, respectively. HPTLC fingerprinting of hydrolyzed chloroform extracts of KAHAW and KM was carried out to determined a number of spots present in them. Conclusions: This study on pharmacognostical standardization of KAHAW and KM will provide useful information for its identification and quality control and can be applied by different manufacturers of these formulations.

Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model

Parkinson's disease (PD) is characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of brain. Oxidative stress and inflammation plays important role in the neurodegeneration and development of PD. Ursolic Acid (UA: 3β-hydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpenoid found in various medicinal plants. Its anti-inflammatory and antioxidant activity is a well-established fact. In this paper, the neuroprotective efficiency of UA in MPTP induced PD mouse model has been explored. For this purpose, we divided 30 mice into 5 different groups; first was control, second was MPTP-treated, third, fourth and fifth were different doses of UA viz., 5mg/kg, 25mg/kg, and 50mg/kg body weight (wt) respectively, along with MPTP. After 21 days of treatment, different behavioral parameters and biochemical assays were conducted. Tyrosine hydroxylase (TH) immunostaining of SN dopaminergic neurons as well as HPLC quantification of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) were also performed. Our results proved that, UA improves behavioral deficits, restored altered dopamine level and protect dopaminergic neurons in the MPTP intoxicated mouse. Among three different doses, 25mg/kg body wt was the most effective dose for the PD. This work reveals the potential of UA as a promising drug candidate for PD treatment.

Neurobehavioral alterations plus transcriptional changes of the heat shock protein 90 and hypoxia inducible factor-1α in the crucian carp exposed to copper

The various physiological alterations caused by copper (Cu) exposure in fish have attracted great interests toward neuronal strategies against Cu toxicity. Here, neurobehavioral activities (including anxiety-like behaviors) and transcriptional levels of heat shock protein (Hsp)90 and hypoxia inducible factor-1alpha (HIF-1α) were evaluated in the crucian carp (Carassius carassius) treated with nominal sub-lethal higher (1.45mg/L) and lower (0.30mg/L) concentrations of CuCl2. Both concentrations accounted for diminished swimming speed and food intake plus a strong preference for the dark side of the light/dark apparatus together with a reduction of crossings between the two compartments with respect to controls. Contextually, Hsp90 and HIF-1α transcripts were largely down- and up-regulated, respectively, in some brain areas such as in the medial part of the dorsal telencephalon (Dm, −52%) and in the ventral part of the ventral telencephalon (Vv, +68%). When carps were transferred to CuCl2-free water, some behaviors were rescued especially for fish previously exposed to 0.30mg/L concentration. In this same condition, Hsp90 mRNA levels were recuperated (−94%) in the medial preglomerular nucleus (NPGm) with respect to exposed fish while HIF-1α mRNA was mostly down-regulated in telencephalic stations. Moreover, recovery capacities of this extraordinary resistant fish was exhibited by evident reductions (−80%) of the dark argyrophilic granules such as in the ventral telencephalon (VTel). Overall, our results point to interesting responses against Cu toxicity involving Hsp90 and HIF-1α transcripts that may constitute early indicators of environmental stressors leading to the repair of metal-induced damages in fish with notable brain plasticity properties.

Age Associated Fluoride Induced Ultra Structural and Biochemical Changes in Rat Brain

Fluoride (F) ingestion is well known to be associated with oxidative stress in experimental animals, but the precise mechanism of its toxicity associated with advancing age has not yet been delineate. The present study attempts to assess the learning and memory capacity of rats using water maze test for cognitive functioning. The markers of oxidative stress i.e., Reacting oxygen species (ROS), protein carbonyl content (PC), lipid peroxide levels (LPx), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) were measured in the brain hippocampus of young and aged rats fed with fluoride (100 ppm) with drinking for 90 days. We observed significant changes of fluoride treated young and aged rat as compared with their respective controls. Lipofuscin content was significantly increased in fluoride treated aged rats. Ultra structural studies of the CA1 region in hippocampus of fluoride exposed rats revealed that the changes were more pronounced in the aged treated rats in terms of presence of clustered lipofuscin, vacuolization, lysosomal degradation and nucleolar fragmentation. On the basis of the results it may conclude that fluoride may be linked with neuro lipofuscinogenesis and alteration in neurobehavioral activity and these changes may be responsible for the development of age related disorders.