Transient functional connections between the developing corticospinal tract and cervical spinal interneurons as demonstrated by c-fos immunohistochemistry

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European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): general report of activities 2000.

The General report of activities is an annual publication providing a detailed progress report of the EMCDDA's activities over a 12-month period. Published every spring, it catalogues the Centre's achievements in each area of its annual work programme. The report is a useful information source for all those seeking comprehensive information on the Centre and its work

Induction of c-fos expression in cervical spinal interneurons after kainate stimulation of the motor cortex in the rat

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Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice

Contains fulltext : 117642.pdf (publisher's version ) (Open Access)Atherosclerosis and apolipoprotein E e4 (APOE4) genotype are risk factors for Alzheimer's disease (AD) and cardiovascular disease (CVD). Sex differences exist in prevalence and manifestation of both diseases. We investigated sex differences respective to aging, focusing on cognitive parameters in apoE4 and apoE knockout (ko) mouse models of AD and CVD. Presynaptic density and neurogenesis were investigated immunohistochemically in male and female apoE4, apoE ko, and wild-type mice. Middle-aged female apoE4 mice showed decreased presynaptic density in the inner molecular layer of the dentate gyrus of the hippocampus. Middle-aged female apoE ko mice showed a trend towards increased neurogenesis in the hippocampus compared with wild-type mice. No differences in these parameters could be observed in middle-aged male mice. Specific harmful interactions between apoE4 and estrogen could be responsible for decreased presynaptic density in female apoE4 mice. The trend of increased neurogenesis found in female apoE ko mice supports previous studies suggesting that temporarily increased amount of synaptic contacts and/or neurogenesis is a compensatory mechanism for synaptic failure. To our knowledge, no other studies investigating presynaptic density in aging female apoE4 or apoE ko mice are available. Sex-specific differences between APOE genotypes could account for some sex differences in AD and CVD

Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice.

Contains fulltext : 51534.pdf (publisher's version ) (Closed access)The amount of the glucose transporter type-1 (GLUT-1) is decreased in the hippocampus and cerebral cortex of AD patients. In this study we therefore wanted to investigate the causal relationship between beta-amyloid (Abeta), GLUT-1 and hippocampal atrophy in the brains of young (8 months) and old (18 months) APP/PS1 mice. METHODS: Abeta and GLUT-1 were visualized immunohistochemically. Abeta load, GLUT-1 amount, capillary density and GLUT-1 amount per capillary density were determined in cortical and hippocampal areas using computer-assisted analysis systems. Hippocampal atrophy was determined by calculating the width of the outer molecular layer of the dentate gyrus (DG). RESULTS: In 18-month-old APP/PS1 mice we found a reduced GLUT-1 amount in the hippocampus but no differences in capillary density. The DG of these mice contained the highest level of Abeta in combination with hippocampal atrophy, and a reduced GLUT-1 amount per capillary density. At 8 months, no differences were observed. The highest Abeta deposition was found in the DG, although fourfold less compared to 18-month-old mice. CONCLUSIONS: We conclude that the GLUT-1 amount and capillary density in both wild type and transgenic mice decrease due to ageing. Further, a decreased amount of GLUT-1 is caused by decreased GLUT-1 amount/capillary density and not due to a reduced capillary density. We suggest that Abeta load in the hippocampus precedes the reduction of GLUT-1. A certain level of Abeta must be reached in the hippocampus, before it affects GLUT-1 amount/capillary density leading to further impairment of energy metabolism and hippocampal atrophy

Effects of chronic paroxetine pretreatment on (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin induced c-fos expression following sexual behavior.

Contains fulltext : 47657.pdf (publisher's version ) (Closed access)Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with ejaculation was investigated. Male Wistar rats that were pretreated with paroxetine (20 mg/kg/day p.o.) or vehicle for 22 days and had received an additional injection with the 5-HT(1A) receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.4 mg/kg s.c.) or saline on day 22, 30 min prior to a sexual behavior test, were perfused 1 h after the sexual behavior test. Brains were processed for Fos-, and oxytocin immunohistochemistry. The drug treatments markedly changed both sexual behavior and the pattern and number of Fos-immunoreactive cells in the brain. Chronic pretreatment with paroxetine caused delayed ejaculation. Acute injection with 8-OH-DPAT facilitated ejaculation in vehicle-pretreated rats, notably evident in a strongly reduced intromission frequency, whereas 8-OH-DPAT had no effects in paroxetine-pretreated rats. Chronic treatment with paroxetine reduced Fos-immunoreactivity in the locus coeruleus, and prevented the increase in Fos-immunoreactive neurons induced by 8-OH-DPAT in the oxytocinergic magnocellular part of the paraventricular nucleus as well as in the locus coeruleus. Since oxytocin and noradrenalin facilitate ejaculation, the alterations in Fos-IR in these areas could connect selective serotonin reuptake inhibitor treatment and 5-HT(1A) receptor activation to ejaculation. Chronic paroxetine treatment and 8-OH-DPAT changed c-fos expression in a number of other brain areas, indicating that Fos-immunohistochemistry is a useful tool to find locations where selective serotonin reuptake inhibitors and 8-OH-DPAT exert their effects

Citalopram combined with WAY 100635 inhibits ejaculation and ejaculation-related Fos immunoreactivity.

Contains fulltext : 48715.pdf (publisher's version ) (Closed access)The role of 5-HT (5-hydroxytryptamine, 5-HT)(1A) receptor activation in the sexual side-effects, in particular delayed ejaculation, of selective serotonin reuptake inhibitors (SSRIs) was studied. Male Wistar rats were treated for 15 days with vehicle, the SSRI citalopram (10 mg/kg/day p.o.), the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexane carboxamide 3HCL (WAY 100635, 0.1 mg/kg/ day s.c.), or both drugs combined. Sexual behavior was assessed weekly. One h after the last sexual behavior test, rat brains were processed for Fos-immunohistochemistry. Acute and chronic citalopram mildly inhibited ejaculation, which was strongly augmented by co-administration of WAY 100635. WAY 100635 alone did not alter sexual behavior. Brain sites associated with ejaculation showed reduced Fos-immunoreactivity in rats treated with both citalopram and WAY 100635. Citalopram reduced Fos-immunoreactivity in the arcuate hypothalamic nucleus, an area that might link serotonergic neurotransmission to ejaculation

Microvascular cerebral blood volume changes in aging APP(swe)/PS1 (dE9) AD mouse model: a voxel-wise approach

Item does not contain fulltextVascular disorders can either be cause or consequence in the pathophysiology of Alzheimer's disease (AD). To comprehensively characterize the occurrence of vascular impairment in a double transgenic mouse model for AD (APP(swe)/PS1(dE9)) during aging, we developed a new method to obtain microvascular relative cerebral blood volume (rCBV(micro)) maps from gradient echo MR imaging by histogram evaluation and we applied a voxel-wise approach to detect rCBV(micro) changes. With this methodology the development of cerebral microvascular impairments can be described in vivo with 0.16�mm isotropic resolution for the whole mouse brain. At 8�months, impaired rCBV(micro) appeared in some cortical regions and in the thalamus, which spreads over several sub-cortical areas and the hippocampus at 13�months. With a ROI-based approach, we further showed that hippocampal rCBV(micro) in 13-month-old wild-type and APP(swe)/PS1(dE9) mice correlates well with capillary density measured with immunohistochemical staining. However, no differences in capillary density were detected between genotypes. The rCBV(micro) values showed no significant correlation with amyloid-� (A�) plaque deposition, A� at blood vessel walls and biochemically measured levels of A�(1-40), A�(1-42) oligomers and fibrillar forms. These results suggest that rCBV(micro) reduction is caused by an impaired vasoactivity of capillaries and arterioles, which is not directly correlated with the amount of A� deposition in parenchyma nor blood vessel walls

White Matter Lesions Are Not Related to beta-Amyloid Deposition in an Autopsy-Based Study.

Contains fulltext : 96523.pdf (publisher's version ) (Open Access)Population-based studies have investigated the relation between beta-amyloid levels in cerebrospinal fluid or plasma and white matter lesions (WMLs). However, these circulating levels of beta-amyloid in cerebrospinal fluid or plasma may not reliably reflect the actual degree of amyloid present in the brain. Therefore, we investigated the relation between WMLs and beta-amyloid plaques and amyloid angiopathy in brain tissue. WML on MRI or CT were rated in 28 nondemented patients whose neuroimaging was available prior to death. beta-amyloid in plaques and arterioles were immunohistochemically stained and quantified in postmortem brain necropsies. WMLs were present in 43% of the total population. Both cortex and periventricular region showed no differences for beta-amyloid deposition in either plaques or blood vessel walls in patients with WMLs compared to those without WMLs. Thus, our results indicate that there is no relation between the degree of WMLs and beta-amyloid deposition in the brain