Papel de la proteína DLK1 en la regulación hipofisaria de las células adiposas en el ratón adulto

To better understand the role of the non-canonical Notch ligand delta-like protein 1 (DLK1), in hormone-producing cells, we studied the cell distribution and subcellular localisation of DLK1 in the pituitary of male adult 129/SvJ mice, and analysed the variations in the hormone-producing cells associated with the lack of this gene in Dlk1 knockout mice. The results obtained showed the presence of DLK1-immunoreactive (ir) cells in all hormone-producing cells of the anterior pituitary. Immunoelectron microscopy showed DLK1-ir in the rough endoplasmic reticulum and inside secretory vesicles, suggesting that DLK1 is released together with pituitary hormones. Moreover, we found that prolactin (PRL)-DLK1-ir cells are in intimate contact with follicle-stimulating hormone (FSH)-ir-DLK1-negative cells. In Dlk1 knockout mice, we detected a significantly lower number of gowth hormone (GH)-ir cells, a reduction in the FSH and PRL immunostaining intensity, and a significant decrease in FSH mRNA expression compared to wild-type mice. An increase in pituitary GH mRNA expression and serum leptin levels was also found. These findings provide evidence supporting several regulatory functions of DLK1 in the pituitary gland. Furthermore, DLK1 showed a roll in the adipose tissue like regulator of pituitary cells and inside adipocyte cells modulating the TSHR expression levels

Differential Aggregation and Phosphorylation of Alpha Synuclein in Membrane Compartments Associated With Parkinson Disease

The aggregation of α-synuclein (α-syn) is a major factor behind the onset of Parkinson’s disease (PD). Sublocalization of this protein may be relevant for the formation of multimeric α-syn oligomeric configurations, insoluble aggregates that form Lewy bodies in PD brains. Processing of this protein aggregation is regulated by associations with distinct lipid classes. For instance, instability of lipid raft (LR) microdomains, membrane regions with a particular lipid composition, is an early event in the development of PD. However, the relevance of membrane microdomains in the regulation and trafficking of the distinct α-syn configurations associated with PD remains unexplored. In this study, using 6- and 14-month-old healthy and MPTP-treated animals as a model of PD, we have investigated the putative molecular alterations of raft membrane microstructures, and their impact on α-syn dynamics and conformation. A comparison of lipid analyses of LR microstructures and non-raft (NR) fractions showed alterations in gangliosides, cholesterol, polyunsaturated fatty acids (PUFA) and phospholipids in the midbrain and cortex of aged and MPTP-treated mice. In particular, the increase of PUFA and phosphatidylserine (PS) during aging correlated with α-syn multimeric formation in NR. In these aggregates, α-syn was phosphorylated in pSer129, the most abundant post-transductional modification of α-syn promoting toxic aggregation. Interestingly, similar variations in PUFA and PS content correlating with α-syn insoluble accumulation were also detected in membrane microstructures from the human cortex of incidental Parkinson Disease (iPD) and PD, as compared to healthy controls. Furthermore, structural changes in membrane lipid microenvironments may induce rearrangements in raft-interacting proteins involved in other neuropathologies. Therefore, we also investigated the dynamic of other protein markers involved in cognition and memory impairment such as metabotropic glutamate receptor 5 (mGluR5), ionotropic NMDA receptor (NMDAR2B), prion protein (PrPc) and amyloid precursor protein (APP), whose activity depends on membrane lipid organization. We observed a decline of these protein markers in LR fractions with the progression of aging and pathology. Overall, our findings demonstrate that lipid alterations in membranous compartments promoted by brain aging and PD-like injury may have an effect on α-syn aggregation and segregation in abnormal multimeric structures

Perspectivas de innovación en gestión, educación ambiental para la adaptación y la mitigación

Esta publicación del libro-foro sobre ciudad y cambio climático responde al aporte de los diferentes profesionales de las entidades públicas y privadas que participaron en calidad de conferencistas, ponentes, panelistas y expositores y compartieron sus experiencias en la ciudad como una contribución al conocimiento de las comunidades acerca de la creciente importancia y consideración de la adaptación y mitigación. Se consideraron acciones de políticas públicas por parte de las administraciones públicas, los sectores económicos y la sociedad, grupos ecológicos y fundaciones ecológicas y de igual forma las acciones y grandes esfuerzos realizados por el Ministerio del Ambiente, el IDEAM, la CAR, la Secretaría de Ambiente, el Jardín Botánico, la Red RAUS y de los grupos de investigación de las universidades

Delta‐like protein 1 in the pituitary‐adipose axis in the adult male mouse

© 2017 The Authors.With the aim of studying delta‐like protein 1 (DLK1) with respect to the relationship between adipocyte leptin and adenohypophyseal hormones, we carried out an immunohistochemical study analysing the presence of receptors for these hormones in the pituitary and adipose cells of male wild‐type (WT) mice (Dlk1+/+) compared to knockout (KO) mice (Dlk1−/−). The mRNA expression of these molecules was also determined using the reverse transcriptase‐polymerase chain reaction. The results obtained showed that, in WT adipose cells, all of the adenohypophyseal hormone receptors were present, with a higher mRNA expression for growth hormone (GH) receptor and thyroid‐stimulating hormone (TSH) receptor. Of the total cells in the anterior pituitary lobe, 17.09±0.9% were leptin receptor (LEPR) immunoreactive (‐IR), mainly in GH‐IR and prolactin (PRL)‐IR cells (41.5±3.8%; 13.5±1.7%, respectively). In Dlk1−/− mice, adipocyte cells showed a significant increase in the TSH receptor mRNA expression level. Moreover, the percentage of LEPR‐IR GH cells showed a statistically significant increase compared to controls, from 41.5±3.8% to 53.1±4.0%. By contrast, only 3.0±0.6% of LEP‐IR anterior pituitary cells were detected in Dlk1 KO mice, as opposed to 6.8±1.1% observed in WT mice. The results suggest that relationships exist between adipocytes and pituitary GH, PRL and TSH cells, in addition to an influence with respect to the synthesis and release of pituitary leptin, particularly in PRL cells.Support was provided by the Consejería de Ciencia y Tecnología JCCM (grants PAI06‐0066‐6930 and PII1I09‐0065‐8194 to C. Díaz).Peer reviewe

Lipid raft ER signalosome malfunctions in menopause in Alzheimer's disease

The increase in the incidence of Alzheimer's disease (AD) in old women may be attributable to estrogen deficiency, and estrogen replacement therapy may be useful in preventing or delaying the onset of this disease. In neuronal membranes, 17b-estradiol interacts with estrogen receptors (mERs) located in lipid raft signalosomes which trigger neuroprotective responses by anchoring to scaffolding caveolin-1 complexed with other proteins. We suggest that mER-signalosome malfunctions in AD and by menopause due to development of aberrations in these microstructures. Here, we report that mER dissociates from a voltage-dependent anion channel (VDAC), and that progressive dephosphorylation of VDAC1 enhances neurotoxicity. mER dissociates from caveolin-1 and other neuroprotective proteins, including insulin-like growth factor 1 receptor beta. Similar signalosome disarrangements are observed in AD patients. Moreover, in AD, lipid rafts exhibit alterations in lipid composition, and these changes cause an increase in liquid-ordered as compared to controls. Together, the data show that AD and menopause lead to disruption in the lipid raft structure, and disfunctioning of ERalpha and other neuroprotectors integrated into these signalosomes