The management of inflammatory bowel disease (IBD) is complex, and requires tight control of disease activity, close monitoring to avoid treatment side effects, healthcare professionals with expertise in IBD and an interdisciplinary, holistic approach. Despite various efforts to standardise structures, processes and outcomes1-8, and due to the high variability at the local, national and international levels, there are still no clear definitions or outcome measures available to establish quality of care standards for IBD patients that are applicable in all contexts and all countries. For this reason, the European Crohn’s and Colitis Organisation (ECCO) supported the construction of a list of criteria summarising current standards of care in IBD. The list comprises 111 quality standard points grouped into three main domains (structure n=31, process n=42, outcomes n=38) and is based on scientific evidence, interdisciplinary expert consensus and patient-oriented perspectives. The list of proposed criteria is intended to represent the position of ECCO regarding the optimum quality of care that should be available to patients. Since healthcare systems and regulations vary considerably between countries, this list may require adaptation at local and national levels. It is recognised that not all these criteria that have been identified as optimal will be available in every unit. However, ECCO will continue its efforts to develop and coordinate projects and initiatives that will help to guarantee optimal quality of care for all IBD patients.

Dementia of the Alzheimer type (DAT) is associated with the accumulation of beta-amyloid (A beta) peptides derived from beta-amyloid precursor protein (APP). Goldstein and coworkers have suggested that APP acts as a cargo receptor connecting post-Golgi vesicles and motor proteins. Sisodia and colleagues have suggested that APP is a passive passenger within the vesicles. Both views predict that one should be able to visualize colocalizations of APP with microtubules, the object of the present investigation. To avoid possible artifacts created by APP overexpression, we studied endogenous expression in a human neuroblastoma cell line (SK-N-SH). Using high resolution fluorescence microscopy and antibodies specific for the amino termini of APP and A beta sequences, we found that endogenous APP and A beta peptide immunoreactivities colocalized with microtubules in interphase cells. Disruption of microtubules, followed by fixation at various time points during repolymerization, allowed us to observe the sequence and timing of these colocalizations in interphase cells. In addition, to our surprise, we found that A beta immunoreactivities colocalize with the mitotic spindle, a bundle of specialized microtubules. Because of the condensed cytoplasm found in neurons, we suggest that SK-N-SH cells might be a more convenient experimental system for exploring the mechanisms that underlie these protein localizations and the pathology that might result from altered APP protein structure and function.

In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.

Alpha-synuclein is a small presynaptic protein associated with both normal synaptic plasticity and neurodegenerative processes. Its normal cellular function, however, remains unknown. Even though it is highly enriched in the brain, its presence was reported in other human adult tissues. In the present study, we examined tissue expression of alpha-synuclein in human and rat prenatal development. Using Western blot analysis, various peripheral tissues from 15 to 23 gestational weeks, human and E19 rat fetuses, along with human and rat adult tissues, were assayed. alpha-Synuclein expression was observed in all fetal human organs examined. In adult human tissues the high expression of alpha-synuclein was maintained in the brain, whereas in other organs the expression was greatly reduced. In contrast, both in fetal and adult rat tissues, alpha-synuclein was only detected in the brain. In addition to a 19-kDa alpha-synuclein band, 36- and 52-kDa immunoreactive bands were observed in all fetal and adult human organs, with the exception of the brain, but their identity remains to be determined. These findings suggest that apart from its function in development of the nervous system, alpha-synuclein has an important function in peripheral tissues as well during normal human prenatal development.

Our previous studies in the rat model of Parkinson’s disease (PD) cholinopathy demonstrated the sleep-related alterations in electroencephalographic (EEG) oscillations at the cortical and hippocampal levels, cortical drives, and sleep spindles (SSs) as the earliest functional biomarkers preceding hypokinesia. Our aim in this study was to follow the impact of a unilateral substantia nigra pars compacta (SNpc) lesion in rat on the cortical and hippocampal sleep architectures and their EEG microstructures, as well as the cortico-hippocampal synchronizations of EEG oscillations, and the SS and high voltage sleep spindle (HVS) dynamics during NREM and REM sleep. We performed unilateral SNpc lesions using two different concentrations/volumes of 6-hydroxydopamine (6-OHDA; 12 μg/1 μl or 12 μg/2 μl). Whereas the unilateral dopaminergic neuronal loss >50% throughout the overall SNpc rostro-caudal dimension prolonged the Wake state, with no change in the NREM or REM duration, there was a long-lasting theta amplitude augmentation across all sleep states in the motor cortex (MCx), but also in the CA1 hippocampus (Hipp) during both Wake and REM sleep. We demonstrate that SS are the hallmarks of NREM sleep, but that they also occur during REM sleep in the MCx and Hipp of the control rats. Whereas SS are always longer in REM vs. NREM sleep in both structures, they are consistently slower in the Hipp. The dopaminergic neuronal loss increased the density of SS in both structures and shortened them in the MCx during NREM sleep, without changing the intrinsic frequency. Conversely, HVS are the hallmarks of REM sleep in the control rats, slower in the Hipp vs. MCx, and the dopaminergic neuronal loss increased their density in the MCx, but shortened them more consistently in the Hipp during REM sleep. In addition, there was an altered synchronization of the EEG oscillations between the MCx and Hipp in different sleep states, particularly the theta and sigma coherences during REM sleep. We provide novel evidence for the importance of the SNpc dopaminergic innervation in sleep regulation, theta rhythm generation, and SS/HVS dynamics control. We suggest the importance of the underlying REM sleep regulatory substrate to HVS generation and duration and to the cortico-hippocampal synchronizations of EEG oscillations in hemiparkinsonian rats.

Neurotrophins are established molecular mediators of neuronal plasticity in the adult brain. We analyzed the impact of aging on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein isoforms, their receptors, and on the expression patterns of multiple 5′ exon-specific BDNF transcripts in the rat cortex and hippocampus throughout the life span of the rat (6, 12, 18, and 24 months of age). ProNGF was increased during aging in both structures. Mature NGF gradually decreased in the cortex, and, in 24-month-old animals, it was 30 % lower than that in adult 6-month-old rats. The BDNF expression did not change during aging, while proBDNF accumulated in the hippocampus of aged rats. Hippocampal total BDNF mRNA was lower in 12-month-old animals, mostly as a result of a decrease of BDNF transcripts 1 and 2. In contrast to the regionspecific regulation of specific exon-containing BDNF mRNAs in adult animals, the same BDNF RNA isoforms (containing exons III, IV, or VI) were present in both brain structures of aged animals. Deficits in neurotrophin signaling were supported by the observed decrease in Trk receptor expression which was accompanied by lower levels of the two main downstream effector kinases, pAkt and protein kinase C. The proteolytic processing of p75NTR observed in 12-monthold rats points to an additional regulatory mechanism in early aging. The changes described herein could contribute to reduced brain plasticity underlying the age-dependent decline in cognitive function.

Disturbance of cholesterol homeostasis in the brain is coupled to age-related brain dysfunction. In the present work, we studied the relationship between aging and cholesterol metabolism in two brain regions, the cortex and hippocampus, as well as in the sera and liver of 6-, 12-, 18- and 24-month-old male Wistar rats. Using gas chromatography-mass spectrometry, we undertook a comparative analysis of the concentrations of cholesterol, its precursors and metabolites, as well as dietary-derived phytosterols. During aging, the concentrations of the three cholesterol precursors examined (lanosterol, lathosterol and desmosterol) were unchanged in the cortex, except for desmosterol which decreased (44 %) in 18-month-old rats. In the hippocampus, aging was associated with a significant reduction in lanosterol and lathosterol concentrations at 24 months (28 and 25 %, respectively), as well as by a significant decrease of desmosterol concentration at 18 and 24 months (36 and 51 %, respectively). In contrast, in the liver we detected age-induced increases in lanosterol and lathosterol concentrations, and no change in desmosterol concentration. The amounts of these sterols were lower than in the brain regions. In the cortex and hippocampus, desmosterol was the predominant cholesterol precursor. In the liver, lathosterol was the most abundant precursor. This ratio remained stable during aging. The most striking effect of aging observed in our study was a significant decrease in desmosterol concentration in the hippocampus which could reflect age-related reduced synaptic plasticity, thus representing one of the detrimental effects of advanced age.

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