Moderate intensity intermittent exercise upregulates neurotrophic and neuroprotective genes expression and inhibits Purkinje cell loss in the cerebellum of ovariectomized rats.

Decreases in estrogen levels due to menopause or ovariectomy may disrupt cerebellar motor functions. This study aimed at investigating the effects of Moderate Intensity Intermittent Exercise (MIEx) on the cerebellum of ovariectomized rats by analyzing neurotrophic and neuroprotective markers, as well as cerebellar motor functions. Thirty-two female Sprague Dawley rats were divided into four groups, i.e. Sham and ovariectomy (Ovx) of non-MIEx (NMIEx) groups, and Sham and Ovx with MIEx groups. MIEx was performed 5 days a week on treadmill for 6 weeks. Motor functions were assessed using rotarod, footprint, open field, and wire hanging tests. Real-time polymerase chain reaction was performed to determine messenger RNA (mRNA) expressions of Pgc-1α, BDNF, synaptophysin, Bcl-2, and Bax. Unbiased stereology was used to estimate the total number of cerebellar Purkinje cells. The Ovx MIEx group had higher Pgc-1α and Bcl-2 mRNA expressions, and number of Purkinje cells, but lower Bax mRNA expression than the Ovx NMIEx group. All motor functions of MIEx groups were better than the Sham and Ovx groups without MIEx. Motor functions on rotarod task, OFT, and FPT correlated significantly with the mRNAs expression of Bcl-2, Bax, BDNF, synaptophysin, Pgc-1α, and the number of cerebellar Purkinje cells in ovariectomized rats. MIEx improves cerebellar neurotrophic and neuroprotective markers, as well as motor functions of ovariectomized rats.

Chlorogenic acid ameliorates memory loss and hippocampal cell death after transient global ischemia.

Chlorogenic acid (CGA) is known to have antioxidant potentials, yet the effect of CGA on brain ischemia has not been sufficiently understood. Brain ischemia such as transient global ischemia disrupts many areas of the brain of rats, including the hippocampus. Male Wistar rats were randomly assigned into five groups, that is, sham-operated (SO), bilateral common carotid occlusion (BCCO), and BCCO+ 15, 30, and 60 mg/kg bw CGA groups (CGA15, CGA30, and CGA60, respectively). Brain ischemia was induced in Wistar rats with BCCO for 20 min followed by intraperitoneal injection of CGA. The rats were examined for the spatial memory in a Morris water maze test on the 3rd day and were euthanized on the 10th day after BCCO. The total number of pyramidal cells was estimated, and the mRNA expressions of Bcl2, Bax, caspase-3, SOD2, SOD1, GPx, ET-1, eNOS, CD31, and VEGF-A were measured. The BCCO group spent less time and distance in the target quadrant than any other group in the spatial memory retention test. The CA1 pyramidal cell numbers in the BCCO and CGA15 groups were lower than in the CGA30 and CGA60 groups. The mRNA expressions of Bcl2, SOD2, and CD31 in the BCCO group were lower than in the CGA15, CGA30, and CGA60 groups. The ET-1 expression was higher in the BCCO and CGA15 groups than in the SO, CGA30, and CGA60 groups. CGA improves the spatial memory and prevents the CA1 pyramidal cell death after BCCO by increasing Bcl2, SOD2, and CD31 expressions and decreasing ET-1 expression.

The neuroprotective effects of an ethanolic turmeric (Curcuma longa L.) extract against trimethyltin-induced oxidative stress in rats.

Introduction: Oxidative stress is known to contribute to the pathogenesis of neurodegenerative disorders. An ethanolic turmeric (Curcuma longa L.) extract containing curcumin has been reported to produce antioxidant effects. Objective: The present study aims to investigate the possible neuroprotective effects of the ethanolic turmeric extract against trimethyltin (TMT)-induced oxidative stress in Sprague Dawley rats. Methods: The ethanolic turmeric extract and citicoline were administered to the TMT exposed rats from day 1 to day 28 of the experiment. The TMT injection was administered on day 8 of the experiment. The plasma and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels, and the activities of the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes in the brain were examined at the end of the experiment. Results: The administration of 200 mg/kg bw of the ethanolic turmeric extract prevented oxidative stress by decreasing the plasma and brain MDA levels and increasing the SOD, CAT, and GPx enzyme activities and GSH levels in the brain. These effects seem to be comparable to those of citicoline. Discussion: The ethanolic turmeric extract at a dose of 200 mg/kg bw may exert neuroprotective effects on TMT-exposed Sprague Dawley rats by preventing them from oxidative stress.

Subchronic Administration of High-Dose Sodium Fluoride Causes Deficits in Cerebellar Purkinje Cells But Not Motor Coordination of Rats.

Fluoride is frequently added to drinking water supplies, various food products, toothpaste, and mouth rinses to prevent tooth damage. However, at high concentrations, fluoride can cause fluorosis and damage to the brain tissue due to its excitotoxicity and oxidative stress effects. The damage of the Purkinje cells of the cerebellum can lead to motor coordination disorders. The present study aimed at investigating the effects of sodium fluoride on the motor coordination and the number of Purkinje cells of the cerebellum of rats. Adult male Wistar rats were divided into four groups, namely a control group which received reverse osmosis distilled water and three treated groups which received sodium fluoride at doses of 5, 10, or 20 mg/kg bw. The treatment lasted for 30 days. The motor coordination of the rats was examined using a rotarod prior and subsequent to the treatments. The number of Purkinje cells was estimated using physical fractionator design. The numbers of Purkinje cells of the F10 and F20 groups were significantly lower than that of the control group. No significant differences in the results of the motor coordination test were found. The administration of sodium fluoride at doses of 10 and 20 mg/kg bw caused a decrease in the number of Purkinje cells of the cerebellum in rats.

The Effects of Light and Moderate Intensity Exercise on the Femoral Bone and Cerebellum of d-Galactose-Exposed Rats.

Aging causes the degeneration of organs of the locomotor system, including the cerebellum and bones. Exercise may reverse this deterioration. d-galactose has been frequently used in rodents to accelerate aging. The present study aimed at investigating the effects of exercise on cerebellar and serum growth factors, motor activity, and the number of bone cells of the femoral head of d-galactose-treated rats. Twenty-four male Wistar rats were divided randomly into four groups, that is, three treated groups injected with 300 mg/(mL·kg) body weight (bw) d-galactose solution daily for 4 weeks, and a control group injected with normal saline. Following the 4-week administration of d-galactose solution, two of the treated groups performed light- (45% VO2max) and moderate- (55% VO2max) intensity exercise, by running on a treadmill 4 × a week for 4 weeks. Locomotor activity was examined in rotarod and open field tests. The cerebellar and serum Insulin-like Growth Factor 1 (IGF-1) and Brain-Derived Neurotrophic Factor (BDNF) levels were measured using enzyme-linked immunosorbent assay (ELISA). The number of osteoblasts and osteoclasts of femoral head was estimated using unbiased stereological methods. It was found that the number of osteoclasts was higher in the d-galactose-treated group than the normal control and moderate-intensity exercise groups. No significant difference between groups was found in the rotarod and open field test performance, IGF-1 and BDNF levels, as well as number of osteoblasts. In conclusion, a 4-week administration of high-dosed-galactose caused the increase of the number of osteoclasts. A subsequent 4-week moderate-intensity exercise reversed this increase to the normal level.

Spatial Memory Disturbance Following Transient Brain Ischemia is Associated with Vascular Remodeling in Hippocampus.

A number of studies have investigated the effects of ischemic injury on functional and cellular characteristics of hippocampus. There is only a limited study on vascular remodeling of it. The present study aimed at examining vascular remodeling in hippocampus and spatial memory disturbances after transient brain ischemia. Male Wistar rats were randomly divided into four groups, i.e. sham operated (SHAM), transient brain ischemia with 1 day reperfusion (IR1), 3 day reperfusion (IR3), and 10 days reperfusion (IR10) groups. Transient brain ischemia was induced by bilateral common carotid artery occlusion (BCCAO). The spatial memory test was performed using the Morris water maze (MWM) in SHAM and IR10 groups. The rats were euthanized at day 1, 3 or 10 after BCCAO depending on the groups. The mRNA expressions of SOD2, Bcl-2, NeuN, eNOS, endothelin-1 (ET-1), CD31, VE-cadherin and vascular remodeling of the hippocampus were examined. There were deteriorations of spatial learning ability in IR10 group. The percentages of SOD2 and Bcl-2, the expression of NeuN, decreased and the vascular remodeling was observed in the ischemic groups. The eNOS and CD31 expressions were less in IR10, the VE-cadherin expression was less in all ischemic groups than in SHAM group, while ET-1 expression in IR1 group was higher than any other groups. The spatial memory deterioration after BCCAO is associated with vascular remodeling in hippocampus, characterized by lumen narrowing and smooth muscle thickening of microvessels.

Turmeric (Curcuma longa L.) extract may prevent the deterioration of spatial memory and the deficit of estimated total number of hippocampal pyramidal cells of trimethyltin-exposed rats.

CONTEXT: Protection of neurons from degeneration is an important preventive strategy for dementia. Much of the dementia pathology implicates oxidative stress pathways. Turmeric (Curcuma longa L.) contains curcuminoids which has anti-oxidative and neuro-protective effects. These effects are considered to be similar to those of citicoline which has been regularly used as one of standard medications for dementia. OBJECTIVE: This study aimed at investigating the effects of turmeric rhizome extract on the hippocampus of trimethyltin (TMT)-treated Sprague-Dawley rats. MATERIALS AND METHODS: The rats were divided randomly into six groups, i.e., a normal control group (N); Sn group, which was given TMT chloride; Sn-Cit group, which was treated with citicoline and TMT chloride; and three Sn-TE groups, which were treated with three different dosages of turmeric rhizome extract and TMT chloride. Morris water maze test was carried out to examine the spatial memory. The estimated total number of CA1 and CA2-CA3 pyramidal cells was calculated using a stereological method. RESULTS: The administration of turmeric extract at a dose of 200 mg/kg bw has been shown to prevent the deficits in the spatial memory performance and partially inhibit the reduction of the number of CA2-CA3 regions pyramidal neurons. DISCUSSION: TMT-induced neurotoxic damage seemed to be mediated by the generation of reactive oxygen species and reactive nitrogen species. Turmeric extract might act as anti inflammatory as well as anti-oxidant agent. CONCLUSIONS: The effects of turmeric extract at a dose of 200 mg/kg bw seem to be comparable to those of citicoline.

Sodium fluoride does not affect the working memory and number of pyramidal cells in rat medial prefrontal cortex.

Fluoride is a chemical compound known to bring about fluorosis. It is thought to disrupt the central nervous system because of its ability to induce excitotoxicity and oxidative stress. Any damage of pyramidal cells in the prefrontal cortex would result in cognitive function and working memory regulation disorders. The present study aimed at investigating the effects of sodium fluoride (NaF) on the working memory and estimated total number of medial prefrontal cortex pyramidal cells of adult male rats. Thirty-two male Wistar rats were assigned into four groups, namely control and three treated groups receiving 5, 10 and 20 mg/kg BW, respectively, of oral NaF solution for 30 days. The working memory test was carried out using a Y-maze. The number of pyramidal cells in the medial prefrontal cortex was estimated using an unbiased stereological method. There was no significant difference among groups in the working memory and number of pyramidal neurons in the medial prefrontal cortex cells.

The effects of black garlic on the working memory and pyramidal cell number of medial prefrontal cortex of rats exposed to monosodium glutamate.

Monosodium glutamate-induced exitotoxicity causes oxidative stress in many brain areas, including the medial prefrontal cortex. The ethanolic garlic (Allium sativum) extract is considered as a neuroprotective substance. The present study aimed at investigating the effects of the ethanolic fermented garlic extract on the working memory and the pyramidal cell number of the medial prefrontal cortex of adolescent male Wistar rats exposed to monosodium glutamate (MSG). Twenty-five rats were randomly divided into five groups. The C- group was given 0.9% NaCl solution. The C + group was given 2 mg/g bw of MSG. The T1, T2, and T3 groups were given MSG and garlic extract (0.0125, 0.025, and 0.05 mg/g bw, respectively). All treatments were conducted for 10 days. The working memory capability of the rats was measured using Y-maze test. The total number of pyramidal cells of the medial prefrontal cortex was estimated using physical fractionator method. The working memory performances of the T1, T2, and T3 groups were significantly better than that of the C + group. There were no significant differences between groups in the estimated total number of pyramidal cell of medial prefrontal cortex. The MSG may not cause the death of neurons, but it may modify neuronal architectures that are sufficient to disrupt memory functions. Black garlic may play a role as an antioxidant agent that prevents the prefrontal cortex from glutamate-induced oxidative stress. It is concluded that the ethanolic fermented garlic extract prevented the working memory impairment following MSG administration.

Effects of treadmill exercise training on cerebellar estrogen and estrogen receptors, serum estrogen, and motor coordination performance of ovariectomized rats.

OBJECTIVES: The present study aims at examining the motor coordination performance, serum and cerebellar estrogen, as well as ERß levels, of ovariectomized rats (as menopausal model) following regular exercise. MATERIALS AND METHODS: Ten female Sprague Dawley rats aged 12 weeks old were randomly divided into two groups; all of which underwent ovariectomy. The first group was treated with regular exercise of moderate intensity, in which the rats were trained to run on a treadmill for 60 min per day for 12 weeks. The second group served as control. Rotarod test was carried out before and after exercise treatment. All rats were euthanized thereafter, and blood and cerebellums of the rats were collected. The serum and cerebellar estrogen as well as cerebellar ERß levels were measured using ELISA assays. RESULTS: The number of falls in the rotarod task of the exercise group was significantly lower than that of control group. The cerebellar estrogen level of the exercise group was significantly higher than that of control group. Accordingly, there was a significantly negative correlation between the number of falls and cerebellar estrogen level in the exercise group. CONCLUSION: The present study shows that a lengthy period of regular exercise improves the cerebellar estrogen level and motor coordination performance in ovariectomized rats.

The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats.

Monosodium glutamate (MSG) is believed to exert deleterious effects on various organs, including the hippocampus, likely via the oxidative stress pathway. Garlic (Alium sativum L.), which is considered to possess potent antioxidant activity, has been used as traditional remedy for various ailments since ancient times. We have investigated the effects of black garlic, a fermented form of garlic, on spatial memory and estimated the total number of pyramidal cells of the hippocampus in adolescent male Wistar rats treated with MSG. Twenty-five rats were divided into five groups: C- group, which received normal saline; C+ group, which was exposed to 2 mg/g body weight (bw) of MSG; three treatment groups (T2.5, T5, T10), which were treated with black garlic extract (2.5, 5, 10 mg/200 g bw, respectively) and MSG. The spatial memory test was carried out using the Morris water maze (MWM) procedure, and the total number of pyramidal cells of the hippocampus was estimated using the physical disector design. The groups treated with black garlic extract were found to have a shorter path length than the C- and C+ groups in the escape acquisition phase of the MWM test. The estimated total number of pyramidal cells in the CA1 region of the hippocampus was higher in all treated groups than that of the C+ group. Based on these results, we conclude that combined administration of black garlic and MSG may alter the spatial memory functioning and total number of pyramidal neurons of the CA1 region of the hippocampus of rats.

Curcumin alters motor coordination but not total number of Purkinje cells in the cerebellum of adolescent male Wistar rats.

OBJECTIVE: The present study aimed at investigating the effects of curcumin on the motor coordination and the estimate of the total number of cerebellar Purkinje cells of adolescent Wistar rats exposed to ethanol. METHODS: The total of 21 male Wistar rats aged 37 d old were divided into three groups, namely ethanol, ethanol-curcumin, and control groups. The ethanol group received 1.5 g/kg ethanol injected intraperitoneally and water given per oral; the ethanol-curcumin group received 1.5 g/kg ethanol injected intraperitoneally and curcumin extract given per oral; the control group received saline injection and oral water. The treatment was carried out daily for one month, after which the motor coordination performance of the rats was examined using revolving drum apparatus at test days 1, 8, and 15. The rats were finally sacrificed and the cerebellum of the rats was further processed for stereological analysis. The estimate of the total number of Purkinje cells was calculated using physical fractionator method. RESULTS: The ethanol-curcumin group performed better than both ethanol and control groups in the motor coordination ability at day 8 of testing (P< 0.01). No Purkinje cell loss was observed as a result of one month intraperitoneal injection of ethanol. CONCLUSION: Curcumin may exert beneficial effects on the motor coordination of adolescent rats exposed to ethanol via undetermined hormetic mechanisms.

The number, size, and type of axons in rat subcortical white matter on left and right sides: a stereological, ultrastructural study.

Abundant evidence indicates important functional differences between the two cerebral hemispheres of humans, although the cellular basis of these differences is unknown. A recent hypothesis proposes that these functional differences depend on differences between sides in the "repertoire" of axonal conduction delays for cortico-cortical axons. In morphological terms this corresponds to differences in caliber, or proportion, of myelinated versus unmyelinated axons. Several behavioural studies have indicated that cerebral asymmetry occurs in rodents, in which rigorous morphological analysis is possible. The hypothesis was therefore tested for the first time in adult male Wistar rats, using transmission electron microscopy and stereological methods. Subcortical white matter was compared between left and right sides in three regions (frontal, parietal, and occipital). The average caliber and numerical density of unmyelinated and myelinated axons was compared between sides and between regions. All data were corrected for shrinkage. No significant differences between sides were found in the average caliber of either type of axon in any region. The numerical density of either type of axon also yielded no significant differences between sides in any region. Significant differences were evident between regions in both caliber and numerical density of the two axonal types, and these quantitative data are reported. The proportion of unmyelinated axons in the lateral white matter was also higher than in previous studies of hemispheric white matter that studied the corpus callosum. The present study provides no evidence supporting the hypothesis that functional hemispheric specialization is due to differences in axonal number, caliber or type.