Prenatal hypoxia-ischemia decreases spatial memory and increases aggression during adolescence.

Prenatal hypoxia-ischemia (HI) is a major cause of mortality and chronic neurological diseases in newborns. HI contributes to the emergence of several neurological disorders such as cognitive and behavioral deficits due to the atypical brain development. This study aimed at assessing the effects of prenatal HI on the spatial memory and aggression of rats during adolescence. Pregnant rats were divided into treatment and control groups. The rats of the treatment groups underwent unilateral ligation of the uterine artery on pregnancy day 7, 12, or 17. The offspring of these rats were tested for spatial memory and aggression when they reached 33 days of age. It has been found that the percentages of alternations in the Y-maze and the number of crossings in the Morris water maze tests of the HI groups were lower than those of the control groups. The total offense and defense aggression scores of the HI groups were higher than those of the control groups. In conclusion, the longer the duration of HI, the more deficits it causes in the spatial memory and aggression of rats during adolescence.

Turmeric extract inhibits apoptosis of hippocampal neurons of trimethyltin-exposed rats.

OBJECTIVES: The aim of the present study was to reveal the possible antiapoptotic effect of turmeric (Curcuma longa Linn.) on the hippocampal neurons of rats exposed to trimethyltin (TMT). BACKGROUND: Oxidative damage in the hippocampus can induce the apoptosis of neurons associated with the pathogenesis of dementiaMETHODS. The ethanolic turmeric extract and a citicoline (as positive control) solution were administered to the TMT-exposed rats for 28 days. The body weights of rats were recorded once a week. The hippocampal weights and imumunohistochemical expression of caspase 3 proteins in the CA1 and CA2-CA3 regions of the hippocampi were examined at the end of the experiment. RESULTS: Immunohistochemical analysis showed that the injection of TMT increased the expression of caspase 3 in the CA1 and CA2-CA3 regions of hippocampus. TMT also decreased the body and hippocampal weights. Furthermore, the administration of 200 mg/kg bw dose of turmeric extract decreased the caspase 3 expression in the CA2-CA3 pyramidal neurons but not in the CA1 neurons. It also prevented the decrease of the body and hippocampal weights. CONCLUSION: We suggest that the 200 mg/kg bw dose of turmeric extract may exert antiapoptotic effect on the hippocampal neurons of the TMT-exposed rats (Tab. 1, Fig. 3, Ref. 49).

Exercise improves hippocampal estrogen and spatial memory of ovariectomized rats.

OBJECTIVE: The present study aimed at examining the effects of regular exercise on hippocampal estrogen and estrogen receptor ß (ERß) levels, as well as the spatial memory of ovariectomized rats. BACKGROUND: A decrease of estrogen levels leads to dysfunctions of hippocampus, including spatial learning and memory. Studies have shown that physical exercise improved spatial memory of ovariectomized rats and was associated with an increased extragonadal aromatization. This in turn affects the expression of estrogen receptors. METHODS: Ovariectomized Sprague Dawley rats were randomly assigned into the two groups, i.e. exercise and control groups. Rats of the exercise group were trained to run on a treadmill. The exercise was performed five times per week for 12 weeks. The spatial memory of rats was measured using the Morris water maze. The hippocampal estrogen and ERß  levels of rats were determined using ELISA. RESULTS: The spatial memory retention of the exercise group was significantly better than that of the control group. The hippocampal estrogen level of the exercise group was significantly higher than that of the control group. CONCLUSION: Regular exercise increases hippocampal estrogen levels and improves spatial memory retention of ovariectomized rats (Tab. 1, Fig. 4, Ref. 53).

Red sorrel (Hibiscus Sabdariffa) prevents the ethanol-induced deficits of Purkinje cells in the cerebellum.

OBJECTIVES: The present study is aimed at investigating the possible protective effects of H. sabdariffa on ethanol-elicited deficits of motor coordination and estimated total number of the Purkinje cells of the cerebellums of adolescent male Wistar rats. METHODS: Forty male Wistar rats aged 21 days were divided into five groups. Na/wtr group was given water orally and injected with normal saline intra peritoneally (ip). Eth/wtr group was given water orally and ethanol (ip). Another three experimental groups (Eth/Hsab) were given different dosages of H. sabdariffa and ethanol (ip). All groups were treated intermittently for the total period of treatment of two weeks. The motor coordination of rats was tested prior and subsequent to the treatments. The rats were euthanized, and their cerebellums were examined. The total number of Purkinje cells was estimated using physical fractionator method. RESULTS: Upon revolving drum test, the number of falls of rats increased following ethanol treatment. There was no significant difference between the total number of falls prior and subsequent to treatment in all Eth/Hsab groups. The estimated total number of Purkinje cells in Eth/Hsab groups was higher than in Eth/wtr group. CONCLUSION: H. sabdariffa may prevent the ethanol-induced deficits of motor coordination and estimated total number of Purkinje cells of the cerebellums in adolescent rats (Tab. 3, Fig. 1, Ref. 42).

High dosage of monosodium glutamate causes deficits of the motor coordination and the number of cerebellar Purkinje cells of rats.

Monosodium glutamate (MSG) has been widely used throughout the world as a flavoring agent of food. However, MSG at certain dosages is also thought to cause damage to many organs, including cerebellum. This study aimed at investigating the effects of different doses of MSG on the motor coordination and the number of Purkinje cells of the cerebellum of Wistar rats. A total of 24 male rats aged 4 to 5 weeks were divided into four groups, namely, control (C), T2.5, T3, and T3.5 groups, which received intraperitoneal injection of 0.9% sodium chloride solution, 2.5 mg/g body weight (bw) of MSG, 3.0 mg/g bw of MSG, and 3.5 mg/g bw of MSG, respectively, for 10 consecutive days. The motor coordination of the rats was examined prior and subsequent to the treatment. The number of cerebellar Purkinje cells was estimated using physical fractionator method. It has been found that the administration of MSG at a dosage of 3.5 mg/g bw, but not at lower dosages, caused a significant decrease of motor coordination and the estimated total number of Purkinje cells of rats. There was also a significant correlation between motor coordination and the total number of Purkinje cells.

The effects of black garlic (Allium sativum L.) ethanol extract on the estimated total number of Purkinje cells and motor coordination of male adolescent Wistar rats treated with monosodium glutamate.

A number of studies have indicated that monosodium glutamate (MSG) might cause negative effects on the nervous system, including in the cerebellum. Garlic (Allium sativum) has long been known as a flavouring agent and a traditional remedy for various illnesses. The present study aimed at investigating the effects of garlic on the motor coordination and the number of Purkinje cells present in rats treated with MSG. A total of 25 male Wistar rats aged 4 to 5 weeks old were used in this study and were divided into five groups, namely a negative control (C-) group, which received 0.9 % NaCl solution, a positive control (C+) group, which received MSG, and three treated groups, which received 2 mg/g bw of MSG and 2.5 mg (T2.5), 5 mg (T5), or 10 mg (T10) of black garlic solution per oral administration (per 200 g bw), respectively. All treatments were carried out for 10 days. Upon the end of the treatment, the motor performance of all rats were tested using the rotarod apparatus. The rats were subsequently sacrificed, and the cerebella of the rats were processed for stereological analyses. It has been found that the number of Purkinje cells of the cerebella of all treated groups were significantly higher than that of the group treated with MSG only. No changes in motor coordination function were observed as a result of MSG treatment.

Mice undernourished before, but not after, weaning perform better in motor coordination and spatial learning tasks than well-fed controls.

Undernutrition of rodents has been claimed to result in long-term behavioural deficits in motor coordination and spatial learning ability, although the literature on this is somewhat conflicting. We have recently been engaged in a study of the effects of either pre- or post-weaning undernutrition on longevity in mice. As part of this ageing study, we have also assessed the effects of such nutritional regimes on motor coordination and spatial learning ability of mice. Motor coordination was tested in 21-week-old control and previously undernourished mice by assessing their ability to remain on a revolving drum. We have found that mice previously undernourished either during the pre- or post-weaning period performed better than controls during some, but not all, of the test days. Spatial learning was tested in 50-58-week-old mice using the Morris water maze. In this instance we found that mice previously undernourished during the pre-weaning period performed better at this task than either controls or mice undernourished for a period after weaning. It seems that undernutrition during the pre-weaning period may, paradoxically, improve the performance of mice in these behavioural tasks compared to controls. Undernutrition after weaning had little or no effect on these behavioural measures. The exact mechanisms involved in causing the observed long-term changes in functional capacity due to a period of undernutrition from conception until weaning age of the mice in our study remain unknown.

Undernutrition during the gestation and suckling periods does not cause any loss of pyramidal neurons in the CA2-CA3 region of the rat hippocampus.

The total number of hippocampal pyramidal cells in the CA2-CA3 region are reported to be unaffected by undernutrition during the gestation period. We hypothesised that this may not be the case in animals subjected to a lengthier period of undernutrition. Wistar rats were undernourished from conception until 21 post-natal days-of-age and killed for examination at 21 and 62 days-of-age. There were between 180-212 thousand pyramidal cells in control animals at both 21 and 62 days of age. Twenty-one-day-old undernourished rats had about 152 thousand such cells and this increased to about 206 thousand by 62 days-of-age. Analysis of variance tests on these data revealed a significant main effect of age but no group or interaction effects. Our experiments, therefore, confirm that these hippocampal pyramidal neurons are relatively spared the adverse effects of undernutrition during early life, even when this is extended to include both the gestation and suckling periods.

Undernutrition during either the pre- or immediate post-weaning period does not affect longevity in Quackenbush mice.

Diet restriction of rodents during a lengthy period of adult life, can lead to a marked increase in their life-span. However, undernutrition during gestation and/or the suckling period is, paradoxically, known to cause long-lasting 'deleterious' deficits in body and brain structure. It remains uncertain whether or not such undernourished rodents also have an altered life-span. We have now investigated whether a short period of undernutrition of mice either before or immediately after the weaning period could modulate their life-span. Female out-bred Quackenbush mice were undernourished for 40 days by standardised procedures either from conception until weaning or from weaning (day 19) till 60-days-of-age and compared to control mice that had been well-nourished throughout their lives. During the course of their life-span, some mice in each group became seriously ill and, because of ethical considerations, were required to be killed before their 'natural' death. The median age of mice at which they were required to be euthanized due to illness was significantly younger in the well-fed control group compared to the two previously undernourished groups. Of those mice that died of natural causes, it was found that about 90% died between about 300-700 (average, 552-570; median, 556-595) days-of-age irrespective of group. Any differences between groups were not statistically significant. There were no significant differences between groups in the numbers of mice that survived beyond the 90th percentile of maximum life-span. Our results provided no evidence that a short period of undernutrition of Quackenbush mice either before or immediately after weaning has significant effects on their life-span. However, there was some evidence that, if it occurred, serious illness happened at a younger age in the well-nourished mice than those in the two diet-restricted groups.

Early life undernutrition alters the level of reduced glutathione but not the activity levels of reactive oxygen species enzymes or lipid peroxidation in the mouse forebrain.

Diet restriction of rodents during adult life is known to cause an increased life span. It has been hypothesised that this increase may be related to effects on the anti-oxidant defence systems. However, it has been suggested that undernutrition during the gestation and pre-weaning may reduce their life span as it is known to have other deleterious effects on a rodent's growth and development. We have now examined the activity levels of some anti-oxidant defence system enzymes and other markers of oxidative stress in mice that have been undernourished from conception until 21 postnatal days of age, followed in some cases by a period of nutritional rehabilitation until 61 days of age. We found that such undernutrition exerted only minimal effects on oxidative stress markers under investigation (ROS enzyme activities, GSH levels, and lipid peroxidation). Only GSH levels were significantly affected by pre-weaning undernutrition. In conclusion, pre-weaning undernutrition may regulate anti-oxidant enzymes at the transcriptional level differently from that at the post-transcriptional, translational, or post-translational levels. The possible effects that these changes at the cellular level, may have on the longevity of the animals remain of great interest and importance.

Pre-weaning undernutrition alters the expression levels of reactive oxygen species enzymes but not their activity levels or lipid peroxidation in the rat brain.

It has been hypothesised that the increased life span commonly observed in rodents that have had their diet restricted after weaning may be related to its effects on the anti-oxidant defence systems. However, undernutrition during the gestation and pre-weaning period is known to have long-term deleterious effects on a rodent's growth and development, and it has been suggested that this may reduce their life span. We have now examined some of the anti-oxidant defence system in rats that have been undernourished from conception until 21 postnatal days-of-age, followed in some cases by a period of nutritional rehabilitation until 62 days of age. We found that such undernutrition could modulate the mRNA expression of Cu/ZnSOD and catalase in some brain regions. However, only catalase showed any undernutrition-induced change of enzyme activity level. There was some evidence that undernourished (but not control) rats had an age-related increase in the level of lipid peroxidation between 21 and 62 days of age, although the group x age interaction was not statistically significant. There was no significant change in the level of reduced glutathione induced by the pre-weaning period of undernutrition. If ROS and the extent of oxidative damage are truly implicated in the determination of life span, our results indicate that this is unlikely to be markedly affected by the relatively small changes we have observed in the anti-oxidant defence systems induced by undernutrition of rats from conception until weaning.

The effects of pre-weaning undernutrition on the expression levels of free radical deactivating enzymes in the mouse brain.

A mild degree of undernutrition brought about by restricting the amount of food in the diet is known to alter the life span of an animal. It has been hypothesised that this may be related to the effects of undernutrition on an animals anti-oxidant defense system. We have therefore, used real-time PCR (rt-PCR) techniques to determine the levels of mRNA expression for manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/ZnSOD), glutathione peroxidase 1 (GPx 1) and catalase in the brains of Quackenbush mice undernourished from conception until 21-post-natal days of age. It was found that 21- and 61-day-old undernourished mice had a deficit in the expression of Cu/ZnSOD in both the cerebellum and forebrain regions compared to age-matched controls. The expression of MnSOD was found to be greater in the cerebellum, but not the forebrain region, of 21-day-old undernourished mice. There were no significant differences in the expression of GPx 1 and catalase between control and undernourished or previously undernourished mice. Our results confirm that undernutrition during the early life of a mouse may disrupt some of the enzymes involved in the anti-oxidant defense systems.