Brain changes in BDNF and S100B induced by ketogenic diets in Wistar rats

AimsWe investigated the effects of ketogenic diet (KD) on levels of tumor necrosis factor alpha (TNF-α, a classical pro-inflammatory cytokine), BDNF (brain-derived neurotrophic factor, commonly associated with synaptic plasticity), and S100B, an astrocyte neurotrophic cytokine involved in metabolism regulation.Main methodsYoung Wistar rats were fed during 8 weeks with control diet or two KD, containing different proportions of omega 6 and omega 3 polyunsaturated fatty acids. Contents of TNF-α, BDNF and S100B were measured by ELISA in two brain regions (hippocampus and striatum) as well as blood serum and cerebrospinal fluid.Key findingsOur data suggest that KD was able to reduce the levels of BDNF in the striatum (but not in hippocampus) and S100B in the cerebrospinal fluid of rats. These alterations were not affected by the proportion of polyunsaturated fatty acids offered. No changes in S100B content were observed in serum or analyzed brain regions. Basal TNF-α content was not affected by KD.SignificanceThese findings reinforce the importance of this diet as an inductor of alterations in the brain, and such changes might contribute to the understanding of the effects (and side effects) of KD in brain disorders.     

Behavioural alterations in rats induced by single prenatal exposure of haloperidol

Haloperidol (50 mg/kg, i.p.) treatment was given once to two different groups of pregnant Charles Foster rats on gestational day 9 and 14, these being respectively the critical periods of neural morphogenesis and rapid neural cell proliferation in this species. Pregnant control rats were similarly treated with equal volume of vehicle. The pups born were subjected to open-field exploratory behaviour and elevated plus-maze behaviour tests of anxiety and learned helplessness test of depression at 9 weeks of age. The results indicate that prenatal haloperidol treatment on gestational day 14 induces a significant increase in open-field ambulation and faecal droppings whereas haloperidol treatment on gestational day 9 caused significantly decreased rearing and unaltered ambulation in rat offsprings. Rat offsprings treated with haloperidol on gestational day 9 and 14 also displayed significant anxiogenic behaviour pattern on elevated plus-maze. Significantly increased number of escape failures were observed in learned helplessness tests indicating presence of depression in haloperidol treated rat offsprings. These behavioural alterations were found to be more marked in rat offsprings treated with haloperidol on gestational day 14. The results suggest that prenatal single exposure of high dose of haloperidol during critical period of neural cell proliferation leaves a lasting imprint on offsprings resulting in abnormal emotional state.     

Enzymatic changes induced by some organophosphorus pesticides in female rats

An evaluation of toxic effects of three organophosphorus pesticides viz. monocrotophos, methyl parathion and dimethoate given orally daily for 90 days was done in terms of enzymatic changes in plasma and liver of female albino rats. A significant decrease was observed in the level of esterases in plasma with all the three pesticides. The activity of acid and alkaline phosphatases and aminotransferases increased significantly in plasma and significantly or marginally in liver with these pesticides. The results are thus indicative of the cellular toxicity of these organophosphates even after their subchronic administration in low doses for a long period.     

Neurobehavioral changes in mice offspring induced by prenatal exposure to acute toxicity of sodium selenite

Selenium is an essential element with a narrow margin between beneficial and toxic effects. This study was aimed to determine the neurobehavioral changes resulted from the prenatal exposure of mice to high doses of sodium selenite during fetal and early postnatal development. Atomic absorption for monitoring the placental transfer of selenium to offspring was employed. The developmental observations as well as the behavioral tests, such as sensory motor reflexes, and learning and memory test in automatic reflex conditioner (shuttle box) (active avoidance responses) were applied. Adult mice was assigned into three groups: the first group was remained as a control group given phosphate buffered saline; the second and the third groups were orally administrated sodium selenite at doses of 1 mg/kg and 4 mg/kg of the diet, respectively started from the 7^th day to the end of the gestation period. Appearance of body hair and opening of eyes of the pups from treated mothers were delayed in a dose-dependent manner. The body weight gain came significantly lower than those of the control especially at the higher dose. Selenite also inhibited the sensory motor reflexes in all elements of acts and postures in a dose dependent manner. The active avoidance training-test indicated that selenite exposure was associated with learning impairment. Acetylcholine recorded a significant decrease in almost all the period of this study. By using atomic absorption, we found a significant high concentration of selenium in the brain, liver and kidney until the 40^th postnatal day, indicating active transfer of selenium from mothers to embryos.     

脑室注射白介素-1β引起的热痛敏作用

实验在SD大鼠上应用脑室微量注射和辐射热测痛的方法,研究了脑内微量注射白介素－1β对大鼠痛阈的影响。实验大鼠分为给药组和对照组,在给药组大鼠脑室注射不同剂量的白介素－1β（5、50和500pg/kg),对照组大鼠脑室注射配药液。白介素－1受体拮抗剂（IL－1ra,50ng/kg)在脑室注射白介素－1β前20min给予。实验以大鼠对光热刺激引起的缩爪反射潜伏期为痛阈指标。结果表明,脑室注射白介素－1β可显著缩短大鼠对光热刺激的缩爪反射潜伏期,并具有剂量依赖性关系。脑室给予500pg/kg的白介素－1β 20min后,大鼠对光热刺激的缩爪反射潜伏期显著缩短,40min时达峰值,然后逐渐恢复。该作用可被白介素－1β受体拮抗剂阻断。结果提示脑中白介素－1β可通过作用于白介素－1受体引起热痛敏作用。     

Behavioral and electrophysiological changes induced by acetyl-L-carnitine in aged freely-moving rats

In chronically-implanted, drug-free, behaving aged Fischer rats, intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.) acetyl-L-carnitine (ALCAR) injections powerfully enhanced motor behavior and head movements aimed at attention and exploratory activity. This effect was dose-dependent and associated with the abolition or substantial reduction of the incidence and duration of the spontaneous EEG generalized hypersynchronous patterns termed High Voltage Spindle (HVS), with an increase in EEG monitored theta activity. The results suggest that ALCAR may stimulate the motivational system and disrupt the hypersynchronous processes by inhibiting the GABAergic thalamic reticular neurons and/or activating the brain stem cholinergic reticular system (pedunculo pontine tegmental, PPT and laterodorsal tegmental, LDT nuclei).     

Lipid peroxidation in liver and colon of methylazoxymethanol treated rats

Weanling male Sprague-Dawley rats were injected via the tail vein with methylazoxymethanol (MAM) acetate at a dose of 70 mg/kg body weight. Measurements of lipid peroxidation were carried out on mitochondrial and microsomal fractions of liver and colonic mucosa at various intervals over the first 24 h following delivery of the carcinogen. Significantly increased levels of peroxidation were observed 3-6 h after treatment in microsomal and mitochondrial fractions of both these tissues. A return to control levels was seen by the end of the first day. These results are discussed in relation to the role of lipid peroxidation in carcinogenesis and the proposed mechanism of tumor prevention by selenium.     

Thorium induced testicular changes in rats.

Daily intraperitoneal administration of thorium nitrate produced progressive morphological and biochemical alterations with the increase in thorium concentration in rat testis. The degenerative changes in the seminiferous tubules increased with the duration of treatment and after 90 days calcification occurred in about 25% of the tubules and in the connective tissue of the tunica albuginea. The activity of adenosine triphosphatase and alkaline phosphatase increased markedly as a result of thorium administration. An attempt has been made to interrelate histopathological and enzymatic changes and the metal concentration in the testicular tissue.     

Modulation of restraint stress induced oxidative changes in rats by antioxidant vitamins

In the present study we examined immobilization stress-induced antioxidant defense changes in rat plasma and also observed the antioxidant effects of pre and post vitamins A, E and C administration (15 mg/Kg of body weight) individually and in combination (vit E + C) on these alterations.Following immobilization stress the circulating activities of superoxide dismutase, catalase and glutathione-S-transferase were decreased, while the level of thiobarbituric acid reactive substances (TBARS) was increased as compared to non-stressed control rats.Post treatment with individual vitamins A, E and C (after exposure to stress) resulted in a less marked alteration of plasma TBARS levels and activities of SOD, GST and catalase as compared to pre vitamin stress or stress alone treatments. Both pre and post vitamin treatments were effective in preventing stress induced derangement of free radical metabolism with a relative dominance by latter. The combined treatment with vitamin E and C did not show any additive antioxidant effect on restraint stress induced altered free radical metabolism, rather a predominant effect similar to vitamin E alone was observed. The prevention of oxidative stress generated in response to restraint stress by the vitamins can be summarized as: vitamin (E + C) i.e. vit E > vit C > vit A, thus combined vitamin (E + C) treatment though showed maximum preventive effect, but was similar to vitamin E treatment alone, in terms of the circulating activities of SOD, GST, catalase and TBARS levels.     

Ultrastructural features of changes in capillaries and atrial cardiomyocytes induced by endotoxin injection]

The experiments on the rabbits and dogs have revealed that in the initial period of endotoxin shock the number of secretory granules in the atrial cardiomyocytes decreases and vascular permeability increases due to transendothelial micropinocytosis. In the intermediate period of endotoxin shock the ultrastructural alterations progress. The development of ultrastructural manifestations of endotoxemia greatly depends on the condition of endocrine heart function.