Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant enzymes

Background: Ageing is associated with gastrointestinal dysfunction, which can have a major impact on quality of life of the elderly. A number of changes in the innervation of the gut during ageing have been reported, including neuronal loss and degenerative changes. Evidence indicates that reactive oxygen species (ROS) are elevated in ageing enteric neurons, but that neurotrophic factors may reduce generation of neuronal ROS. Two such factors, glial cell line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) have also been found to protect enteric neurons against oxidative stress induced cell death of enteric ganglion cells in vitro. We have investigated the possible roles of neurotrophic factors further, by examining their expression in the gut during ageing, and by analysing their effects on antioxidant enzyme production in cultures of enteric ganglion cells. Results: Analysis of the expression of GDNF and its receptors c-Ret and GFR α − 1 in rat gut by RT-PCR showed that expression continues throughout life and into ageing, in both ad libitum(AL) and calorically-restricted (CR) animals. Levels of expression of GDNF and GFR α − 1 were elevated in 24 month AL animals compared to 24 month CR animals, and to 24 CR and 6 month control animals respectively. The related factor Neurturin and its receptor GFR α − 2 were also expressed throughout life, the levels of the GFR – α-2(b) isoform were reduced in 24 m AL animals. Immunolabelling showed that c-Ret and GFR α − 1 proteins were expressed by myenteric neurons in ageing animals. GDNF, but not NT-3, was found to increase expression of Cu/Zn superoxide dismutase and catalase by cultured enteric ganglion cells. Conclusions: The neurotrophic factors GDNF and neurturin and their receptors continue to be expressed in the ageing gut. Changes in the levels of expression of GDNF , GFR α-1 and GFR α-2(b) isoform occurred in 24 m AL animals. GDNF, but not NT-3, increased the levels of antioxidant enzymes in cultured enteric ganglion cells, indicating a possible mechanism for the reported protective effect of GDNF against menadione-induced neuronal apoptosis in the ageing gut. Together these data suggest that GDNF family members may play a protective role in the gut throughout life, and support the suggestion that dysregulation of neurotrophic factor support could contribute to neuronal ageing in the gut

Small molecule activators of the Trk receptors for neuroprotection

The neurotophin signaling network is critical to the development and survival of many neuronal populations. Especially sensitive to imbalances in the neurotrophin system, cholinergic neurons in the basal forebrain are progressively lost in Alzheimer's disease. Therapeutic use of neurotrophins to prevent this loss is hampered, however, by a number of pharmacological challenges. These include a lack of transport across the blood-brain barrier, rapid degradation in the circulation, and difficulty in production. In this review we discuss the evidence supporting the neurotrophin system's role in preventing neurodegeneration and survey some of the pharmacological strategies being pursued to develop effective therapeutics targeting neurotrophin function

MÖSSBAUER SPECTROSCOPY OF IRON COMPOUNDS PRESENT IN THE PROFILE OF AN URANIUM DEPOSIT

Plusieurs échantillons prélevés dans le profil d'un gisement uranifère du district de la Sierra Pintada (Mendoza, Argentine) ont été étudiés par spectroscopie Mössbauer. La présence de spectres hyperfins magnétiques à certaines profondeurs sont plus riches en uranium, confirme le mécanisme de transport d'uranium et la réduction bactérienne suggérés précédemment.Several samples taken in the profile of an uranium deposit of the Sierra Pintada district (Mendoza, Argentina) were studied by means of Mössbauer spectroscopy. The presence of magnetic hyperfine spectra at certain depths, which are richer in uranium, confirm previously suggested uranium transport mechanism and bacterial reduction

Propiedades estructurales y magnéticas de hematitas puras sometidas a aleamiento mecánico en aire

Se llevó a cabo tratamiento mecanicoquimico de polvo de a -Fe 2 O 3 (hematita) en aire y en un líquido dispersante (etanol), utilizando un molino planetario de bolas. Se investigó la influencia de la atmósfera y la duración del tiempo de molienda en la transformación de a -Fe 2 O 3 . Medidas de difracción de rayos X (DRX) y espectroscopia Mössbauer revelan transformación parcial de a -Fe 2 O 3 a ?-Fe 2 O 3 (Maghemita) para tiempos prolongados de molienda en aire, mientras que solo fase de a -Fe 2 O 3 fue obtenida para la molienda en etanol. Parámetros de red y tamaños de granos han sido calculados de los patrones DRX para los diferentes tiempos y condiciones de molienda