Upregulation of neuronal nicotinic receptor subunits alpha4, beta2, and alpha7 in transgenic mice overexpressing human acetylcholinesterase

Neuronal nicotinic receptor binding sites as well as mRNA levels encoding for subunits α4, β2, and α7 were analysed in 3-mo-old transgenic mice generated with a neuronal overexpression of human acetylcholinesterase and in age-matched controls. The acetylcholinesterase transgenic mice display progressive cognitive impairment in spatial learning and memory. We here report a significantly increased [³H]epibatidine and [¹²⁵I]αbungarotoxin binding in the cortex and the caudate putamen of these mice. Quantitative in situ hybridization showed significant upregulation of mRNA corresponding to the nicotinic receptor subunits α4, β2, and α7 in various brain regions in the transgenic mice compared to nontransgenic controls. Our results suggest that disruption of balanced cholinergic transmission by constitutive overexpression of acetylcholinesterase is accompanied by variable upregulation of several nicotinic receptor subtypes, in particular these associated with cholinergic terminals participating in compensatory response.     

Patients' needs during the year after a suicide attempt

OBJECTIVE: We first studied whether changes of needs were influenced by randomly allocated telephone interventions between 1 and 12 months after a suicide attempt in addition to treatment as usual. These were aimed at improving motivation for professional treatment. As a secondary analysis we investigated the frequency and changes of needs during this period and if changes were related to other outcome measures. METHOD: One month after a suicide attempt 216 patients were randomised to two telephone interventions or to no such interventions within 1 year. The Camberwell Assessment of Need (CAN) was used to evaluate 22 different need areas at 1 and 12 months. Other outcome measurements used were Global functioning axis V (GAF), psychological symptoms (SCL-90, GSI) and scale of suicide ideation (SSI). RESULTS: Of 178 patients who were followed up, 140 had been rated by CAN at both 1 and 12 months. Changes of needs did not differ between the randomised groups. At 1 month the patients had a mean number of 5.1 +/- 2.4 needs and 2.4 +/- 1.5 of these were considered as unmet. The most frequently reported needs concerned health aspects, basic needs and social needs. At 12 months needs concerning health aspects were significantly reduced, while basic needs and social needs were not. Changes of GAF explained 21 % and changes of GSI 4 % of the variance of the reduction of needs. CONCLUSIONS: After 12 months, needs in health aspects, basic needs and social needs were still common. A structured evaluation of the patient's needs seems to be helpful when planning treatment after a suicide attempt.     

Sex differences in episodic memory: the influence of intelligence

The influence of estimated intelligence (group assessment of WAIS-R( S)) on sex differences in face recognition, as well as verbal and non-verbal episodic memory tasks was examined in 99 women and 88 men between 20 and 40 years of age. Results showed that men performed at a higher level than women on the WAIS-R(S) subtest Information, whereas the opposite was true for Digit symbol. Women performed at a higher level than men on the verbal episodic memory tasks and on face recognition, but there were no sex differences on the non-verbal episodic memory task. Estimated intelligence for both men and women was positively associated with most episodic memory measures, the exception being face recognition in women. In face recognition, there was no association to estimated intelligence, suggesting that face recognition performance in women is unrelated to several basic cognitive processes.     

Interaction of a muscarinic cholinergic agonist on acetylcholine and dopamine receptors in the monkey brain studied with positron emission tomography

The effects on the binding to cholinergic and dopaminergic receptors in the brain during continuous intravenous infusion of the muscarinic cholinergic receptor agonist milameline (CI-979) were studied in the rhesus monkey by means of positron emission tomography. Binding to milameline cholinergic receptors was quantified using the muscarinic receptor antagonist [(11)C]-N-methyl-4-piperidinylbenzilate ([(11)C]NMP), and the effects on nicotine receptor binding were measured with (S)-[(11)C-methyl]nicotine. Changes in the binding of the D(2) dopamine receptor antagonist [(11)C]raclopride were measured as well. The binding of [(11)C]NMP increased in most brain regions with the infusion of increasing doses of milameline from 0.5 to 10 microg/kg/h. (S)-[(11)C-methyl]nicotine binding was unchanged or increased somewhat. Binding of [(11)C]raclopride to the D(2) dopaminergic receptors in the striatum of the brain increased by 10 +/- 4% following 2 microg/kg/h of milameline. The results suggest a possible action of milameline both on presynaptic muscarinic receptor subtypes as well as dopamine levels dependent on the receptor reserve of the muscarinic receptor subtypes.     

Energy expenditure assessed by heart rate and doubly labeled water in young athletes

PURPOSE: To compare total energy expenditure (TEE) estimated by the FLEX heart rate (HR) method with that measured by the doubly labeled water (DLW) technique in young speed skaters. We hypothesized that the accuracy of FLEX HR-estimated TEE would be affected by a) the definition of the FLEX HR and b) the type of training regimen. METHODS: Eight young athletes (mean age 18.2 +/- 1.3 yr) underwent measurements during two 10-d training periods: an off-season period with voluntary training (predominantly running) and a preseason period mainly focused on skating technique training. TEE was measured simultaneously by the DLW and FLEX HR methods. FLEX HR1 was defined as the mean of the HRs during all resting calibration activities and the lowest HR during exercising calibration activities. FLEX HR2 was defined as the mean of the highest HR during resting activities and the lowest HR during exercising. RESULTS: ANOVA showed that FLEX HR1 was significantly lower than FLEX HR2 (mean of both periods; 77 +/- 5 vs 84 +/- 6 beats.min(-1); P = 0.004). TEE values obtained by DLW were 16.8 +/- 3.8 and 16.9 +/- 2.9 MJ.d(-1) in the two periods, respectively. TEE values calculated from FLEX HR1 were 17.8 +/- 3.6 and 17.4 +/- 2.6 MJ.d(-1), and those from FLEX HR2 17.1 +/- 3.1 and 17.0 +/- 2.7 MJ.d-1, respectively. No significant period (P = 0.83) or method (P = 0.44) effect on TEE was observed. CONCLUSION: FLEX HR-estimated TEE was not affected by the definition of the FLEX HR or by the type of training regimen as compared with TEE measured by the DLW method in young athletes.     

Smoking during pregnancy: a way to transfer the addiction to the next generation?

Many epidemiological studies support a relationship between maternal smoking during pregnancy and adverse neurobehavioral effects later in life. Prenatal exposure to tobacco seems to increase the risks for cognitive deficits, attention deficit/hyperactivity disorder, conduct disorder, criminality in adulthood and a predisposition in the offspring to start smoking and alcohol abuse. Nicotine readily crosses the placenta and the fetuses of mothers who smoke are exposed to relatively higher nicotine concentrations than their mothers. In the fetal brain nicotine can activate nicotinic receptors which play an important role during development of the brain. A direct specific action on the developing human brain is plausible during the major part of the prenatal life, since the nicotinic receptors are already present in the brain during the first trimester.     

Adverse effects of gasoline on the skin of exposed workers

Gasoline is widely used as a solvent in industry. To study its adverse effects on the skin and to understand their mechanisms, a matched epidemiological study (1:1, 52 exposed workers and 52 control subjects) was developed. Information about general conditions, history of dermatosis, changes in skin after exposure to gasoline, etc., was obtained. Ceramide, fatty acid and cholesterol collected from the backs of the hands were analyzed by high‐performance thin‐layer chromatography (HPTLC), because stratum corneum lipids play a predominant rôle in maintaining the physiological function of skin. The results showed that prevalences of hyperkeratosis, dryness, onychosis and dermatitis were clearly higher in exposed workers than in the control group, prevalence ratios being 3.33 (p<0.05), 3.00 (p<0.001), 11.25 (p<0.001), 5.00 (p<0.001), respectively. Fissures and onychorrhexis were the common symptoms in exposed workers. The stratum corneum lipid levels of ceramide, fatty acid and cholesterol were significantly lower in the exposed group than in the control group (p<0.05). Findings indicated that prolonged or repeated contact with gasoline could cause fissuring of the skin and nail disorders, and that the mechanism was perhaps depletion of stratum corneum lipids.     

Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats

OBJECTIVES: Severe postnatal infection leads to a systemic inflammatory response with release of cytokines and glucocorticoids, representing a stressful event for the newborn child. The purpose of this study was to mimic this situation and to study the effects of early postnatal endotoxin exposure of female rat pups on metabolic, endocrine and anthropometric variables in adulthood. DESIGN: Female pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth. RESULTS: Six hours after injection, LPS-treated rats had higher corticosterone levels than controls. As adults, LPS-exposed female rats showed increased insulin sensitivity (P<0.05), measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity (P<0.05) and increased skeletal muscle mass in comparison with controls (P<0.05). Basal ACTH and corticosterone levels in LPS-treated rats were elevated (P<0.05), as were corticosterone levels after exposure to a novel environment stress (P<0.05). The adrenals were morphologically changed and enlarged (P<0.05) in LPS-exposed rats at 11 weeks of age, and a higher density of hypothalamic but not hippocampal glucocorticoid receptor protein was found in the LPS-treated rats (P<0.05). Furthermore, circulating progesterone levels were lower (P<0.05) and testosterone tended to be higher. CONCLUSION: The results indicate that postnatal exposure to LPS leads to increased insulin sensitivity in the adult female rat. In addition, LPS-treated rats showed changes in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. This study suggests that postnatal exposure to an endotoxin such as LPS can induce specific programming of neuroendocrine regulation, with long-term consequences in adult life.     

Increased insulin sensitivity and decreased body weight in female rats after postnatal corticosterone exposure

OBJECTIVE: Glucocorticoids are important for normal brain development. Elevation or removal of these hormones can permanently modify the structure and function of the fetal brain. The purpose of this study was to examine the effects of postnatal corticosterone exposure of female pups on metabolic, endocrine and anthropometric variables in adulthood. DESIGN: Female pups were given subcutaneous injections of corticosterone (5 mg/kg, CORT) or vehicle 3 and 5 days after birth. RESULTS: From 6 weeks of age, the CORT rats weighed significantly less than did controls, with diminished fat depots, decreased serum levels of leptin and reduced food intake. Adult CORT rats showed increased insulin sensitivity, measured by hyperinsulinemic, euglycemic clamp (5 mU/kg/min), as compared with controls. CORT rats had lower basal corticosterone levels and lower corticosterone levels 15 and 90 min after exposure to stress. CONCLUSION: The results indicate that postnatal exposure to corticosterone leads to increased insulin sensitivity, low body weight with diminished fat depots, leptin and food intake. This suggests that postnatal exposure to corticosterone induces specific programming, with consequences in adult life.