Geraniol improved memory impairment and neurotoxicity induced by zinc oxide nanoparticles in male wistar rats through its antioxidant effect.

AIMS: Zinc oxide nanoparticles (ZnO-NPs) are currently applied in food and pharmaceutical industries whose neurotoxic effect on the central nervous system (CNS) is a major concern. Considering the pharmacological properties (antioxidant, anti-inflammatory) of the geraniol (GE), we aimed to investigate the efficacy of geraniol on ZnO-NPs neurotoxicity. MATERIALS AND METHODS: We used 32 male Wistar rats, randomly assigned to four groups (n = 8): Control, GE (daily received 100 mg/kg of GE by gavage), ZnO-NPs (received intraperitoneal injection of 75 mg/kg of ZnO-NPs twice a week), and ZnO-NPs + GE (received both GE and ZnO-NPs at same doses above during 4 weeks). Morris water maze (MWM) and Y-maze tasks were done to evaluate learning and memory function. Biochemical assays were done to measure total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and ZnO-NPs bioaccumulation. Nissl and H&E staining were performed for histological evaluations. KEY FINDINGS: The results of behavioral study revealed that GE improved learning and memory impairment induced by ZnO-NPs. Moreover, neuroprotective effect of GE significantly decreased pathological parameters such as necrosis and gliosis, and consequently increased the number of nerve cells in the cortex and different hippocampal areas. Furthermore, biochemical studies demonstrated that GE significantly increased antioxidant indices (namely, TAC, SOD, and GPX) and reduced oxidative stress marker (MDA) and Zn bioaccumulation in ZnO-NPs treated animals. SIGNIFICANCE: Our results provide experimental evidence to further investigate the precise mechanisms underlying the geraniol as a promising therapeutic approach for improvement of cognitive function and neurotoxicity induce by ZnO-NPs.

Protective effect of raisin (currant) against spatial memory impairment and oxidative stress in Alzheimer disease model.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive pathological changes of the brain. A number of studies demonstrated compelling evidence of the importance of oxidative processes in AD pathogenesis. Raisin contains polyphenol, phenolic acid, and tannin compounds, which have antioxidant and anti-inflammatory properties. The present study was aimed to evaluate the protective effect of raisin on neurobehavioral and histological changes in rats with Alzheimer. Methods: Animal model of AD was induced by intraperitoneal injection of aluminium chloride for 60 days (100 mg/kg body weight). During these 60 days both Alzheimer's and control rats were given 6 g of raisin per rat. At the end of the treatment, blood was collected for biochemical assessment. We used a Morris water task and passive avoidance test to assess spatial memory. Results: Our results showed that aluminium exposure significantly decreased the memory in the MWT and passive avoidance test, but in the raisin + AlCl3 group, it significantly increased spatial memory in both tests. Also, Aluminium exposure significantly increased malondialdehyde (MDA) and decreased ferric reducing ability of plasma (ferric reducing/antioxidant power (FRAP)), while treatment with raisin significantly decreased MDA and increased FRAP in plasma of blood. Discussion: Our findings showed that raisin has a neuroprotective effect and improves the spatial memory in AD animal models.

Spatial Memory and Antioxidant Protective Effects of Raisin (Currant) in Aged Rats.

Diets rich in fruits and vegetables can prevent age-related diseases. This research was conducted to evaluate the effects of raisin consumption on the spatial memory and morphometric parameters of brain tissue in aging rats. Old rats (20 months of age) were divided into 2 groups: control and raisin, with 6 rats in each group. The raisin group received 6 g of raisins daily in addition to their food and water for 90 days. After treatments, all animals were evaluated by behavioral tests to assess spatial memory and learning alongside other tests including the ferric reducing antioxidant power (FRAP), malondialdehyde, and histological examinations. The results showed that there are significant differences in the Morris water task and passive avoidance learning of behavioral tests and biochemical tests (FRAP and thiobarbituric acid reactive substances) between the two groups. The histological study indicated that the cell count of the hippocampus, the diameter of the lateral ventricle, and area of the corpus callosum in the raisin group changed in comparison with the control group but they were not significant. The results demonstrated that raisins significantly raise antioxidant levels in blood and promotes cognitive and motor performance in aging rats.

Oxytocin-mediated social enrichment promotes longer telomeres and novelty seeking.

The quality of social relationships is a powerful determinant of lifetime health. Here, we explored the impact of social experiences on circulating oxytocin (OT) concentration, telomere length (TL), and novelty-seeking behaviour in male and female rats. Prolonged social housing raised circulating OT levels in both sexes while elongating TL only in females. Novelty-seeking behaviour in females was more responsive to social housing and increased OT levels than males. The OT antagonist (OT ANT) L-366,509 blocked the benefits of social housing in all conditions along with female-specific TL erosion and novelty-seeking deficit. Thus, females seem more susceptible than males to genetic and behavioural changes when the secretion of endogenous OT in response to social life is interrupted. Social enrichment may, therefore, provide a therapeutic avenue to promote stress resiliency and chances of healthy aging across generations.

Intergenerational Sex-Specific Transmission of Maternal Social Experience.

The social environment is a major determinant of individual stress response and lifetime health. The present study shows that (1) social enrichment has a significant impact on neuroplasticity and behaviour particularly in females; and (2) social enrichment in females can be transmitted to their unexposed female descendants. Two generations (F0 and F1) of male and female rats raised in standard and social housing conditions were examined for neurohormonal and molecular alterations along with changes in four behavioural modalities. In addition to higher cortical neuronal density and cortical thickness, social experience in mothers reduced hypothalamic-pituitary-adrenal (HPA) axis activity in F0 rats and their F1 non-social housing offspring. Only F0 social mothers and their F1 non-social daughters displayed improved novelty-seeking exploratory behaviour and reduced anxiety-related behaviour whereas their motor and cognitive performance remained unchanged. Also, cortical and mRNA measurements in the F1 generation were affected by social experience intergenerationally via the female lineage (mother-to-daughter). These findings indicate that social experience promotes cortical neuroplasticity, neurohormonal and behavioural outcomes, and these changes can be transmitted to the F1 non-social offspring in a sexually dimorphic manner. Thus, a socially stimulating environment may form new biobehavioural phenotypes not only in exposed individuals, but also in their intergenerationally programmed descendants.

Lack of Social Support Raises Stress Vulnerability in Rats with a History of Ancestral Stress.

Stress is a primary risk factor for psychiatric disorders. However, it is not fully understood why some stressed individuals are more vulnerable to psychiatric disorders than others. Here, we investigated whether multigenerational ancestral stress produces phenotypes that are sensitive to depression-like symptoms in rats. We also examined whether social isolation reveals potentially latent sensitivity to depression-like behaviours. F4 female rats born to a lineage of stressed mothers (F0-F3) received stress in adulthood while housed in pairs or alone. Social isolation during stress induced cognitive and psychomotor retardation only in rats exposed to ancestral stress. Social isolation also hampered the resilience of the hypothalamic-pituitary-adrenal axis to chronic stress and reduced hippocampal volume and brain-derived neurotrophic factor (BDNF) expression. Thus, synergy between social isolation and stress may unmask a latent history of ancestral stress, and raises vulnerability to mental health conditions. The findings support the notion that social support critically promotes stress coping and resilience.

Evidence for Ancestral Programming of Resilience in a Two-Hit Stress Model.

In a continuously stressful environment, the effects of recurrent prenatal stress (PS) may accumulate across generations and alter stress vulnerability and resilience. Here, we report in female rats that a family history of recurrent ancestral PS facilitates certain aspects of movement performance, and that these benefits are abolished by the experience of a second hit, induced by a silent ischemia during adulthood. Female F4-generation rats with and without a family history of cumulative multigenerational PS (MPS) were tested for skilled motor function before and after the induction of a minor ischemic insult by endothelin-1 infusion into the primary motor cortex. MPS resulted in improved skilled motor abilities and blunted hypothalamic-pituitary-adrenal (HPA) axis function compared to non-stressed rats. Deep sequencing revealed downregulation of miR-708 in MPS rats along with upregulation of its predicted target genes Mapk10 and Rasd2. Through miR-708 stress may regulate mitogen-activated protein kinase (MAPK) pathway activity. Hair trace elemental analysis revealed an increased Na/K ratio, which suggests a chronic shift in adrenal gland function. The ischemic lesion activated the HPA axis in MPS rats only; the lesion, however, abolished the advantage of MPS in skilled reaching. The findings indicate that MPS generates adaptive flexibility in movement, which is challenged by a second stressor, such as a neuropathological condition. Thus, a second "hit" by a stressor may limit behavioral flexibility and neural plasticity associated with ancestral stress.

Prevalence of flatfoot among school students and its relationship with BMI.

OBJECTIVE: The aim of this study was to analyze the relation between the flat-footedness and obesity. MATERIALS AND METHODS: A total of 1158 school children (653 male and 505 female) participated in this cross sectional descriptive study. According to their age, children were divided into three groups for each gender (6-10, 11-13, 14-18 years old). Diagnosis and severity of flatfoot was assessed in using the Dennis method. BMI of children were calculated as body weight divided by height squared (kg*m-2). RESULTS: Majority (83.9%) of respondents had normal feet. The prevalence of flatfoot was 16.1% with a decreasing trend with age. Boys had a higher frequency of flatfoot than girls; however the difference was not significant (p > 0.05). The prevalence of flatfoot was 17.5% in boys and 14.5% in girls. The percentage of overweight and obese children was 10.3%. A significant difference in the prevalence of flatfoot occurred between; under-weight (13.9%), normal-weight (16.1%), overweight (26.9%), and obese (30.8%); children. CONCLUSION: The increasing prevalence of childhood obesity is one of the most serious health challenges across the globe, and a positive correlation between increased BMI; and flatfoot is one of the potential complications.

Regional vulnerability of the hippocampus to repeated motor activity deprivation.

Spontaneous vertical and horizontal exploratory movements are integral components of rodent behavior. Little is known, however, about the structural and functional consequences of restricted spontaneous exploration. Here, we report two experiments to probe whether restriction in vertical activity (rearing) in rats could induce neuro-hormonal and behavioral disturbances. Rearing movements in rats were deprived for 3h/day for 30 consecutive days by placing the animal into a circular tunnel task. Rats temporarily deprived of rearing behavior showed elevated plasma corticosterone levels but no detectable psychological distress and/or anxiety-related behavior within an elevated plus maze. However, rats emitted a greater number of 22-kHz ultrasonic vocalizations and spent significantly more time vocalizing than controls when deprived of their rearing behavior. Despite intact spatial performance within wet- and dry-land spatial tasks, rearing-deprived rats also exhibited a significant alteration in search strategies within both spatial tasks along with reduced volume and neuron number in the hippocampal subregion CA2. These data suggest a new approach to test the importance of free exploratory behavior in endocrine and structural manifestations. The results support a central role of the CA2 in spontaneous exploratory behavior and vulnerability to psychological stress.

Topographical disorientation after ischemic mini infarct in the dorsal hippocampus: whispers in silence.

Silent focal ischemic mini infarcts in the brain are thought to cause no clinically overt symptoms. Some populations of hippocampal cells are particularly sensitive to ischemic events, however, rendering hippocampal functions especially vulnerable to ischemia-induced deficits. The present study investigated whether an otherwise silent ischemic mini infarct in the hippocampus (HPC) can produce impairments in spatial performance in rats. Spatial performance was assessed in the ziggurat task (ZT) using a 10-trial spatial learning protocol for 4 days prior to undergoing hippocampal ischemic lesion or sham surgery. Hippocampal silent ischemia was induced by infusion of endothelin-1 (ET-1), a potent vasoconstrictor, into either the dorsal or the ventral hippocampus (dHPC and vHPC). When tested postoperatively in the ZT using a standard testing protocol for 8 days, rats with hippocampal lesions exhibited no spatial deficit. Although spatial learning and memory in the ZT were not affected by the ET-1-induced silent ischemia, rats with dHPC stroke showed more returns when navigating the ZT as opposed to the vHPC rats. Comparison of region-specific HPC lesions in the present study indicated that dorsal hippocampal function is critically required for topographic orientation in a complex environment. Topographic disorientation as reflected by enhanced return behaviors may represent one of the earliest predictors of cognitive decline after silent ischemic insult that may be potentially traced with sensitive clinical examination in humans.

Stress inhibits psychomotor performance differently in simple and complex open field environments.

Stress affects psychomotor profiles and exploratory behavior in response to environmental features. Here we investigated psychomotor and exploratory patterns induced by stress in a simple open-field arena and a complex, multi-featured environment. Groups of rats underwent seven days of restraint stress or no-stress conditions and were individually tested in three versions of the ziggurat task (ZT) that varied according to environmental complexity. The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis due to stress procedure was evaluated by the pre- and post-stress levels of circulating corticosterone (CORT). Horizontal activity, exploration, and motivation were measured by the number of fields entered, the time spent in the central fields, path length and speed, and stop duration. In addition, vertical exploratory behavior was measured by the times rats climbed onto ziggurats. Stress-induced psychomotor changes were indicated by reduced path length and path speed and increased duration of stops only within the complex arena of the ZT. Rats in stress groups also showed a significant decline in the vertical movements as measured by the number of climbing onto ziggurats. No stress-induced changes were revealed by the simple open-field arena. The exploratory patterns of stressed animals suggest psychomotor inhibition and reduced novelty-seeking behaviors in an environment-dependent manner. Thus, multi-featured arenas that require complex behavioral strategies are ideally suited to reveal the inhibitory effects of stress on psychomotor capabilities in rodents.

Stress enhances return-based behaviors in Wistar rats during spatial navigation without altering spatial performance: improvement or deficit?

Stress is frequently reported to be deleterious to spatial learning and memory. However, there are many instances in which spatial performance is not affected by stress. This discrepancy observed across different studies, in addition to the animals' strain and gender, may be caused by the type of the task employed to assess stress-related behavioral changes. The present experiments set out to investigate the effects of repeated restraint stress (3h/21 days) on spatial performance within the two wet-land (Morris water task; MWT) and dry-land (the ziggurat task; ZT) tasks for spatial learning and memory in adult male Wistar rats. All rats were tested before and after stress treatment. Stressed rats gained less weight than controls. Stress also enhanced circulating corticosterone (CORT). We did not observe a deleterious effect of stress on spatial learning and memory in either of the tasks: both groups successfully performed the wet- and dry-land tasks across all spatial testing days, indicating intact spatial cognition in control and stress rats. However, daily restraint stress for 21 days significantly caused enhancement in rats' memory-dependent returns during the goal-directed investigation in the ZT. The number of returns on learning days was not affected by repeated restraint stress. Return-based spatial investigation induced by stress only on memory days in the dry-land task, not only emphasize on the task-dependent nature of stress-related alterations, it may reveal one of the silent, but arguably deleterious effects of stress on spatial memory in Wistar rats.

Comparison of Morphometric Aspects of Light and Electron Microscopy of the Hypoglossal Nerve between Young and Aged Male Wistar Rats.

OBJECTIVE: Age-related changes occur in many different systems of the body. Many elderly people show dysphagia and dysphonia. This research was conducted to evaluate quantitatively the morphometrical changes of the hypoglossal nerve resulting from the aging process in young and aged rats. MATERIALS AND METHODS: Through an experimental study ten male wistar rats (4 months: 5 rats, 24 months: 5 rats) were selected randomly from a colony of wistars in the UWC. After a fixation process and preparation of samples of the cervical portion of the hypoglossal nerve of these rats, light and electron microscopic imaging were performed. These images were evaluated according to the numbers and size of myelinated nerve fibers, nucleoli of Schwann cells, myelin sheath thickness, axon diameter, and g ratio. All data were analyzed by Mann-Whitney, a non-parametric statistical test. RESULTS: In light microscope, numbers of myelinated nerve fibers, the mean entire nerve perimeters, the mean entire nerve areas and the mean entire nerve diameters in young and aged rats' were not significantly different between the two groups. In electron microscope, numbers of myelinated axons, numbers of Schwann cell nucleoli and the mean g ratios of myelinated axon to Schwann cell in young and aged rats were not significantly different. The myelinated fiber diameters, the myelin sheath thicknesses, myelinated axon diameters and the mean g ratio of axon diameter to myelinated fiber diameter in young and aged fibers were significantly different. CONCLUSION: The mean g ratio of myelinated nerve fibers of peripheral nerves stabilizes at the level of 0.6 after maturation and persists without major change during adulthood. This ratio of axon diameter to fiber diameter (0.6) is optimum for normal conduction velocity of neural impulses. Our study indicated that the g ratio of myelinated nerve fiber of the hypoglossal nerve decreased prominently in aged rats and can be a cause of impairment in nerve function in old age. Thus, prospective studies concerning electrophysiological and conductive properties of the peripheral nerve could be useful to clarify further the effects of aging on peripheral nerves.