Postnatal handling alters glucocorticoid, but not mineralocorticoid messenger RNA expression in the hippocampus of adult rats

Postnatal handling alters hypothalamic-pituitary-adrenal (HPA) responses to stress in the rat. Handling also increases hippocampal glucocorticoid receptor density, and this effect appears to form, in part at least, the basis for the effect of handling on HPA responsiveness to stress. In the present study we have used in situ hybridization techniques to examine the effect of postnatal handling on the expression of glucocorticoid and mineralocorticoid receptor mRNAs in various cell fields of the dorsal hippocampus in adult rats. Grain counting analysis over individual cells showed that postnatal handling significantly increased (40-50%) glucocorticoid receptor mRNA in all hippocampal cell fields. In contrast, handling had no effect on mineralocorticoid receptor mRNA expression. These findings are consistent with the results of receptor binding studies showing that handling increases hippocampal glucocorticoid receptor, but not mineralocorticoid receptor density. Thus, the increase in glucocorticoid receptor binding in handled animals is likely associated with altered rates of receptor biosynthesis. Moreover, the handling effect is quite specific, altering glucocorticoid receptor, but not mineralocorticoid receptor mRNA expression. The mechanism(s) whereby glucocorticoid receptor gene expression is permanently increased by postnatal handling remains to be determined.     

Neonatal handling alters brain organization but does not influence recovery from perinatal cortical injury.

Handling rat pups by removing them from the nest during the preweaning period has been shown to influence brain and behavioral development. The authors hypothesized that handling rats with perinatal (Day 4) medial frontal cortex removals might attenuate behavioral deficits and reverse dendritic atrophy associated with such an injury. On the day after surgery, pups were removed from the nest for 15 min, 3 times per day until weaning. Animals were tested as adults in the Morris water task and on skilled reaching. Handled animals showed no improvement in behavioral performance. The handling procedure led to a decrease in dendritic length in parietal cortex, but spine density was unchanged. No therapeutic advantage was observed following the preweaning handling of brain-injured rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diazepam alters caffeine-induced effects on beta-endorphin levels in specific rat brain regions

The present study was conducted to evaluate the effects of caffeine and the benzodiazepine agonist diazepam, and a combination of both on beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light: 12-hour dark illumination cycle were used in this study. Caffeine (10 mg/kg), diazepam (2 mg/kg) or a combination of caffeine (10 mg/kg) and diazepam (2 mg/kg) were administered intraperitoneally to rats at 11:00 hr. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection, the brains were immediately removed; the cortex, hippocampus, hypothalamus and midbrain were dissected and their B-EN levels measured by radioimmunoassay. Caffeine administration significantly increased B-EN levels in the cortex. Similarly, administration of diazepam alone resulted in a significant increase of B-EN levels in cortex. However, concurrent administration of diazepam and caffeine resulted in higher increase of B-EN levels in cortex. No significant changes in B-EN levels were detected in hippocampus and midbrain after administration of either caffeine or diazepam alone. On the other hand, when diazepam and caffeine were concurrently administered a significant increase of B-EN levels were observed in the midbrain. Moreover, administration of diazepam alone resulted in a significant increase of B-EN levels in hypothalamus. This increase was still observed following concurrent administration of diazepam and caffeine. These results clearly indicate that diazepam alters caffeine-induced effects on B-EN in specific rat brain regions.     

Early malnutrition and postnatal changes in brain and behavior in the mouse

The effects of early undernutrition were studied by rearing mice in small, intermediate or large litters (respectively 4, 8 or 16 pups). Measures of reflexes and electrocorticographic activity applied from birth to weaning indicated that malnutrition resulted in a clear ontogenetic retardation which was followed by permanent body and brain stunting. The mice from the large litters were characterized by increased exploratory activity and by lower avoidance learning ability as measured 45 days after nutritional rehabilitation.     

Chronic antipsychotic treatment alters glycine-stimulated NMDA receptor binding in rat brain

A growing body of studies have confirmed that autoantibodies against beta 1-adrenoceptors are present in different types of cardiomyopathy. This suggests that they play a role in the pathophysiology of the disease. This article will review the data indicating the presence of anti-beta 1-adrenoceptor autoantibodies in cardiomyopathy. It will focus upon their structural and functional properties which could explain their possible role in the induction and development of cardiomyopathic diseases.     

Global cerebral ischemia and reperfusion alters NMDA receptor binding in canine brain

We employed a canine model to test whether binding to the N-methyl-D-aspartate (NMDA) class of glutamate receptor channels is altered by global cerebral ischemia and/or reperfusion. Ischemia was induced by 10-min cardiac arrest, followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4, and 24 h. In vitro autoradiography was performed on frozen brain sections with three radioligands: [3H]glutamate (under conditions to label the NMDA site), [3H]glycine, and [3H]MK-801. Modest decreases in [3H]glutamate and [3H]MK-801 binding were seen in several regions of hippocampus, and parietal and temporal cortex at early times after reperfusion, with values returning toward control by 24 h. In the striatum, a different pattern was seen: [3H]glutamate and [3H]MK-801 binding increased 50-200% at 0.5-4 h after the start of reperfusion, returning toward control levels by 24 h. These increases correlate with findings of increased sensitivity to NMDA-stimulated release of dopamine from striatal tissue in the same model (Werling et al., 1993), and suggest that changes in tissue receptors may contribute to the selective vulnerability to ischemic damage during the first hours following reperfusion.     

Serotonin transporter expression in rat brain regions and blood platelets: aging and glucocorticoid effects

Hyperactivity of the hypothalamus-pituitary-adrenal axis is more common in elderly depression than in younger cohorts and glucocorticoids are known to influence serotonergic systems. The current study explores the interaction of glucocorticoids with aging on serotonin transporter expression and function. Continuous infusions of dexamethasone (26 days) reduced transporter expression in the aged brain but the ability of imipramine to inhibit synaptosomal [3H]serotonin uptake was unimpaired. These effects were unique to aged animals, as prior work with young adults found no effects of dexamethasone on transporter expression. In contrast to the effects in the brain, there were no differences in platelet transporter expression between young and old rats nor did dexamethasone treatment affect the values in the aged group: thus, the platelet may not reliably model these aspects of CNS function. The results suggest that there are basic biologic differences in the effects of glucocorticoids in aged vs. young brain that could contribute to lowered effectiveness to antidepressants in elderly depression; if transport capacity is already reduced by the effects of increased glucocorticoids, further inhibition of transport by antidepressants would have proportionally less impact on synaptic serotonin concentrations.     

Changes in dietary fatty acids alter phospholipid fatty acid composition in selected regions of rat brain

1. Eighty rats were randomized into four groups receiving one of the following diets: rat chow containing (1) 6% soybean oil, (2) 6% primrose oil, (3) 6% fish oil, (4) a combination of 4.5% primrose and 1.5% fish oil. 2. Following two months of each regimen, the rats were sacrificed by microwave irradiation and the brain's fatty acid composition was analysed with gas chromatography for each of the following regions: frontal cortex, striatum, occipital cortex, hippocampus, hypothalamus, cerebellum and pituitary. 3. Linoleic acid was decreased by both primrose and fish oil supplementations. The fish oil substitution resulted in a significant elevation of 20:3n-6, a decrease of 22:4n-6 and a non-significant decrease of 20:4n-6, probably reflecting inhibition of delta-5-desaturation. At the same time the fish oil diet significantly elevated 22:5n-3 while 22:5n-6 was decreased. 4. The primrose oil diet lowered the n-3/n-6 ratio in all regions except in the cerebellum. In contrast, the fish oil diet elevated the n-3/n-6 ratio in all regions. 5. The results demonstrate that changes in dietary fat composition can alter the fatty acid composition of the adult rat brain and that these effects are region specific. 6. This is of interest since metabolites of essential fatty acids may be involved in physiological and pathological processes in the brain and it has been hypothesized that dietary intake of fats may influence the outcome of psychiatric disorders such as schizophrenia.     

Early adversity alters attention and locomotion in adult Sprague-Dawley rats.

This study investigated the effects of prenatal stress and its interaction with artificial rearing (AR) on adult rat behavior. Pregnant dams underwent restraint stress from Gestational Day 10 to 21. After parturition, pups were raised by their mothers or in the AR paradigm, with or without stroking stimulation. In adulthood, rats were tested on prepulse inhibition (PPI), locomotor activity, elevated plus-maze, and spatial working memory. There were main effects and interactions of both prenatal stress and AR on activity. Additional stimulation reduced activity in nonstressed AR rats but increased activity in prenatally stressed AR rats. AR altered PPI and plus-maze behavior whereas additional stimulation partially reversed these effects. This study demonstrates that prenatal experiences can modulate the effects of postnatal treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early postnatal changes in sexual dimorphism of catecholamine and indoleamine content in the brain of prenatally stressed rats

Sexual dimorphism in catecholamine and indoleamine content in the brain preoptic area and mediobasal hypothalamus was studied in 10-day-old rat pups whose mothers had been exposed to the daily 1-h immobilization stress during the last week of pregnancy. Concentration of noradrenaline in the preoptic area and 5-hydroxyindoleacetic acid in the mediobasal hypothalamus of the prenatally stressed male offspring as well as dopamine content in the mediobasal hypothalamus and 5-hydroxyindoleacetic acid content in the preoptic area of the females were increased by 59%, 45%, 34%, 76%, respectively. Dopamine content in the preoptic area of the female pups was decreased. In addition, an increase of 5-hydroxytryptamine metabolism in the female preoptic area has been revealed. As a result of prenatal stress, sex-related differences in noradrenaline and 5-hydroxyindoleacetic acid concentrations in the preoptic area and those in dopamine concentration in the mediobasal hypothalamus disappeared. The suggestion is made that the early changes in sexual dimorphism of the brain catecholamines and 5-hydroxytryptamine metabolism in prenatally stressed rats may be responsible for the development of the long-term disorders of sexual differentiation of the neuroendocrine functions.     

Typical food allergens for pollinosis in selected regions of Poland. Multiagent studies

The analysis of the incidence of the positive prick test with food allergens among patients with pollen allergy was performed. The 270 patients with pollinosis from four allergy centres in Poznań, Lód? and Katowice were examined. In each centres the different results were obtained. The influence for this had the different status socioeconomic of the patients, the regional habits of eating, and often eating the new products in our country. However, among examination patients the most positive test with food allergens from all centres were nuts, celery, rye flour, carrot, strawberry, pork and beans. The succession of this food allergens were changed in four examination centres in respect to the number of made prick test but the same allergens had been repeated. These results premises to establish the list of the allergens that are needed during diagnosis the patients with pollinosis.     

Early postnatal X-irradiation of the hippocampus and discrimination learning in adult rats.

Trained Long-Evans rats with X-irradiation produced degranulation of the hippocampal dentate gyrus in the acquisition and reversal of simultaneous visual and tactile discriminations in a T-maze in 3 experiments. The experiments employed the same treatment, apparatus, and procedure but varied in task difficulty. In the brightness and roughness discriminations, the irradiated Ss were not handicapped in acquiring or reversing discriminations of low or low-moderate task difficulty. However, these Ss were handicapped in acquiring and reversing discriminations of moderate and high task difficulty. In a Black/White discrimination in which the stimuli were restricted to the goal-arm walls, the irradiated Ss were handicapped in the acquisition (low task difficulty) and reversal (moderate task difficulty) phases of the task. Results suggest that the irradiated Ss were not handicapped when the noticeability of the stimuli was high, irrespective of modality used, but were handicapped when the noticeability of the stimuli was low. Results are consistent with the hypothesis that rats with hippocampal damage are inattentive due to hyperactivity. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A differential response of diffuse brain injury on the concentrations of endothelin and nitric oxide in the plasma and brain regions in rats

In the present study, we hypothesized that acute diffuse brain injury (DBI) in rats would produce an increase in endothelin-1 (ET-1), a potent vasoconstrictor, and/or nitric oxide (NO), a potent vasodilator, in plasma and brain areas in rats. DBI was induced in anesthetized male Sprague-Dawley rats (350-400 g) using a 350 g weight dropped from 1 meter height impact through a device designed by Marmarou et al., 1994. Blood plasma and brain tissue (cerebral cortex, diencephalon and brain stem) samples were collected for estimation of ET-1 and NO at zero or 6 h from rats (n = 6) subjected to DBI as well as control rats (n = 6), i.e., not subjected to DBI. In a separate group of animals, cerebral blood flow (CBF) was recorded at 0, 5, 10, 15, 30, 60, 120, 240 and 360 min after induction of DBI or sham-DBI. Acute DBI produced a significant decrease in CBF at 120 min after induction of DBI. Plasma levels of ET-1 was found to be significantly increased (from 0.89 +/- 0.09 to 2.09 +/- 0.29 pg ml-1), at 6 h following DBI. DBI produced a significant decrease in the levels of ET-1 in diencephalon (from 70.97 +/- 9.47 to 57.64 +/- 2.65 pg g-1). In contrast to ET-1, DBI produced a significant increase in the concentrations of NO in the diencephalon, cerebral cortex and brain stem at 6 h post DBI. It appears that DBI-induced increase in the levels of NO in brain regions which might be down regulating the synthesis of ET-1 in diencephalon. It is concluded that ET and NO homeostatic mechanisms may play a role in the regional and vascular responses associated with acute DBI.     

Early adversity and serotonin transporter genotype interact with hippocampal glucocorticoid receptor mRNA expression, corticosterone, and behavior in adult male rats.

Despite its importance for development, relatively little is known about how allelic variation interacts with both pre- and postnatal stress. We examined the interaction between serotonin transporter (5-HTT) genotype, prenatal and postnatal stress on glucocorticoid receptor (GR) mRNA expression, corticosteroid stress responses, and behavior in adult male rats. Prenatal stress involved a daily restraint of pregnant dams from gestational Day 10–21. Postnatal stress involved raising pups after parturition either by their mothers (MR) or in the artificial rearing (AR) paradigm, with or without additional “licking-like” stroking stimulation. 5-HTT genotype, hippocampal GR mRNA level, corticosteroid stress response, and behaviors including startle response, prepulse inhibition (PPI), and locomotor activity were measured in adult male rat offspring. We found significant genotype by prenatal stress interactions for hippocampal GR mRNA levels and for the corticosterone stress responses in adulthood. In contrast, behavioral endpoints tended to be more clearly affected by an interaction between genotype and postnatal environment. These findings suggest that allelic variation in the 5-HTT gene interacts with the prenatal environment to affect the hypothalamic-pituitary-adrenal (HPA) axis physiology and the postnatal environment to affect behavior. These results are the first to indicate a role for genetic variation in the 5-HTT gene in physiology and behavior in the rat. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Expression of glucocorticoid receptor gene isoforms in corticotropin-secreting tumors

The molecular basis of Cushing's disease is not known. One of the most characteristic features of such tumors is their resistance to corticosteroid feedback at the pituitary level. We have hypothesized that abnormalities of the glucocorticoid receptor (GR) gene might play a role in the development of Cushing's disease via an increase in the relative production of the nonligand-binding splice variant of the GR, GR beta, known to exert dominant negative effects over the ligand-binding isoform, GR alpha. Alternatively, a change in overall GR expression, or mutations of some functional domains of the GR gene, might be involved in the pathogenesis of corticotroph tumors. We studied 22 tumors (17 pituitary ACTH-secreting tumors, 2 ectopic ACTH-producing tumors, 2 prolactinomas, and 1 nonfunctioning adenoma) and three normal pituitaries. RT-PCR was performed with primers specific to GR alpha and GR beta complementary DNA, followed by Southern blotting using an internal probe, and the ratio of the two bands quantitated by densitometry. We also assessed the overall expression of GR relative to the message of both the POMC gene and a housekeeping gene. Single-strand conformation polymorphism analysis of the DNA-binding domain and splice junction region of the gene was also performed. GR alpha messenger RNA was expressed at 37.3-fold +/- 5.7 (range, 32 to 46) excess, as compared with the GR beta subform. This pattern was observed both in the tumor samples and in the normal pituitaries used as controls. A majority of the ACTH-secreting tumors (16/19), including the ectopic secretors, showed variable but increased overall GR expression, whereas 3 tumors showed an expression approximately equivalent to the normal controls; however, no correlation was found between these two groups and the response to the high-dose dexamethasone test, nor was there any correlation with tumor histology. No mutations were found in any of the tumors by PCR-single-strand conformation polymorphism analysis. In conclusion, although both pituitary and ectopic ACTH-secreting tumors are at least partially glucocorticoid-resistant, no significant abnormalities in the relative expression of the two main GR subforms were observed in a series of such tumors. Additionally, mutations of regions critical to normal function of the receptor do not seem to be a frequent event in these tumors.     

Pneumocystis carinii alters surfactant protein A concentrations in bronchoalveolar lavage fluid

To understand better the interaction between surfactant protein A (SP-A), human immunodeficiency virus (HIV) and Pneumocystis carinii pneumonia (PCP), we measured SP-A from bronchoalveolar lavage (BAL) fluid in immunosuppressed patients (HIV-positive [HIV+] and HIV noninfected [HIV-]) who were examined for possible pneumonia. Forty-five HIV+ patients, 16 with PCP and no other pathogen (HIV+/Pc) and 29 with no evidence of pulmonary pathogen (HIV+ controls), were compared with 6 HIV- patients with PCP (HIV-/Pc) and 11 control patients with no underlying disease (controls). Despite a similar inflammatory response in the HIV-infected patients whether they had PCP or not, we found increased BAL SP-A concentrations in HIV+/Pc patients as compared with HIV+ control patients (HIV+/Pc: median, 10.3 micrograms/ml; range, 2.8 to 24.3 micrograms/ml; HIV+ control: median, 1.9; range, 0.06 to 3.83 micrograms/ml; p < 0.05). The amount of SP-A in the HIV+ control group was significantly lower than healthy, uninfected volunteers, suggesting that HIV itself may lower SP-A levels. Six HIV+/Pc patients underwent BAL after 21 days of therapy and showed complete resolution of the P. carinii organism. There was a significant drop in the amount of SP-A at follow-up lavage (initial mean, 14.1 micrograms/ml; follow-up mean, 7.4 micrograms/ml; p < 0.02). We also found a significant correlation between the amount of P. carinii and the amount of SP-A in the BAL fluid (Spearman rank, 0.74; p < 0.01). We conclude that SP-A content is increased in HIV+ patients with PCP. The relationship between SP-A concentration and the abundance of P. carinii present in the BAL fluid may be related to SP-A binding to P. carinii or to alterations in surfactant protein homeostasis.     

Early postnatal overfeeding as an etiopathogenetic factor in adult obesity

In 114 men and to a less degree in 111 women, significant positive relations were found between the weight gain during the first trimenon of postnatal life and the body weight per body length in adulthood. In contrast, there were not observed any significant relations between birth weight, birth length or weight gain during the second trimenon of postnatal life and the body weight per body length in adulthood. These findings suggest that over-nutrition during the first three months of life may be considered an essential risk factor for the development of obesity and its complications.