Exploring the Intricacies of Neurogenic Niches: Unraveling the Anatomy and Neural Microenvironments.

Neurogenesis is the process of forming new neurons from neural stem cells (NSCs). In adults, this process takes place in specific areas of the brain, known as neurogenic niches. These regions have unique anatomical features that have been studied in animal models and in the human brain; however, there are differences between these models that need to be addressed. The most studied areas are the subventricular zone, the lateral and latero-dorsal walls of the lateral ventricles, and the dentate gyrus of the hippocampus (Hp), which are known as the canonical areas. Other, less-studied niches, such as the hypothalamus, the cerebellum, and the amygdala, are known as non-canonical areas. Anatomy occupies a relevant place in adult neurogenesis, in which the tissue architecture and cellular location are necessities for the interaction and release of diverse molecules that allow this phenomenon. The cell arrangement within the niche and the location of the niche itself are of particular relevance to the state in which the NSCs are found. Consequently, the majority of previous discoveries have been related to pathology. While many studies are based on animal models, discoveries related to neurogenesis in humans have also been made; however, in this case, opinions vary, leading to extensive controversy in recent years. In this review, we address the anatomical characteristics of the different brain regions to better understand their relationships within neurogenesis.

Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha.

Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6-month-old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor-alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging.

Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?

Harmonic mechanisms orchestrate neurogenesis in the healthy brain within specific neurogenic niches, which generate neurons from neural stem cells as a homeostatic mechanism. These newly generated neurons integrate into existing neuronal circuits to participate in different brain tasks. Despite the mechanisms that protect the mammalian brain, this organ is susceptible to many different types of damage that result in the loss of neuronal tissue and therefore in alterations in the functionality of the affected regions. Nevertheless, the mammalian brain has developed mechanisms to respond to these injuries, potentiating its capacity to generate new neurons from neural stem cells and altering the homeostatic processes that occur in neurogenic niches. These alterations may lead to the generation of new neurons within the damaged brain regions. Notwithstanding, the activation of these repair mechanisms, regeneration of neuronal tissue within brain injuries does not naturally occur. In this review, we discuss how the different neurogenic niches respond to different types of brain injuries, focusing on the capacity of the progenitors generated in these niches to migrate to the injured regions and activate repair mechanisms. We conclude that the search for pharmacological drugs that stimulate the migration of newly generated neurons to brain injuries may result in the development of therapies to repair the damaged brain tissue.

Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action.

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKCα activation and promotes transforming growth factor alpha (TGFα) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.

Vitamin D deficiency as a potential risk factor for accelerated aging, impaired hippocampal neurogenesis and cognitive decline: a role for Wnt/ß-catenin signaling.

Vitamin D is an essential fat-soluble vitamin that participates in several homeostatic functions in mammalian organisms. Lower levels of vitamin D are produced in the older population, vitamin D deficiency being an accelerating factor for the progression of the aging process. In this review, we focus on the effect that vitamin D exerts in the aged brain paying special attention to the neurogenic process. Neurogenesis occurs in the adult brain in neurogenic regions, such as the dentate gyrus of the hippocampus (DG). This region generates new neurons that participate in cognitive tasks. The neurogenic rate in the DG is reduced in the aged brain because of a reduction in the number of neural stem cells (NSC). Homeostatic mechanisms controlled by the Wnt signaling pathway protect this pool of NSC from being depleted. We discuss in here the crosstalk between Wnt signaling and vitamin D, and hypothesize that hypovitaminosis might cause failure in the control of the neurogenic homeostatic mechanisms in the old brain leading to cognitive impairment. Understanding the relationship between vitamin D, neurogenesis and cognitive performance in the aged brain may facilitate prevention of cognitive decline and it can open a door into new therapeutic fields by perspectives in the elderly.

[Hyperuricemia in shift workers: a cross-sectional study in a spanish chemical factory]. / Hiperuricemia y menor actividad física en trabajadores a turnos: estudio transversal en una industria química española.

OBJECTIVE: There is no clear consensus over the findings of research into shift work and cardiovascular risk factors, such as those present in the metabolic syndrome (MetS). This is further confounded by the varying definitions of MetS and shift work. Our objective was to learn about the link between shift work, lifestyles and cardiovascular health in chemical factory workers. METHODS: Cross-sectional analytical study, carried out 2018-2019; data obtained from annual occupational health check-ups. 515 workers chosen, with a 1:3 ratio (shifts/no shifts). Variables collected: MetS, arterial hypertension, obesity, abdominal adiposity and biochemical alterations (glucose, total cholesterol, HDL cholesterol, triglycerides and uric acid). Explanatory variables: age, gender, tobacco consumption, physical activity and shift work. Besides the usual descriptions, both non-adjusted and adjusted bivariate logistic regression were performed, producing Odds Ratio (OR) values with 95% CI. RESULTS: The non-adjusted logistic regression showed that shift workers performed less physical activity (OR=0.22; 95% CI=0.14-0.35; p<0.001) and had lower HDL cholesterol levels (OR=2.1; 95% CI=1.2-3.8; p<0.05), plus a higher rate of hypertriglyceridemia (OR=2.05; 95% CI=1.3-3.2; p<0.01) and hyperuricemia (OR=2.7; 95% CI=0.9-2.7; p<0.001). In the logistic regression adjusted for age, gender, tobacco consumption, physical activity and shift work only the prevalence of hyperuricemia was higher in shift workers (OR=2.25; 95% CI=1.1-4.6; p<0.05), as well as with less moderate/high physical activity (OR=0.19; 95% CI=0.12-0.31; p<0.001). CONCLUSIONS: While no link was found between shift work and increased smoking or a higher cardiovascular risk, there was evidence of an association with high uric acid levels and less moderate/high physical activity.

OBJETIVO: Las conclusiones de las investigaciones sobre turnicidad y factores de riesgo cardiovascular, como los que forman parte del síndrome metabólico (SMet), no son unánimes. Las distintas definiciones del SMet y el trabajo por turnos las dificultan. Nuestro objetivo fue conocer la asociación entre el trabajo por turnos y los hábitos de vida y la salud cardiovascular de los trabajadores de una industria química. METODOS: Se realizó un estudio transversal analítico entre 2018 y 2019. Los datos se obtuvieron de los exámenes de salud anuales. Se seleccionaron 515 trabajadores, estableciendo una relación de 1:3 (por turnos / sin turnos). Se recogieron como variables resultado: SMet, hipertensión arterial, obesidad, adiposidad abdominal y alteraciones bioquímicas (glucosa, colesterol total, colesterol HDL, triglicéridos y ácido úrico). Las variables explicativas fueron: edad, sexo, consumo de tabaco, actividad física y turnicidad. Aparte de los descriptivos habituales, se realizó una regresión logística bivariada cruda y otra ajustada, determinando valores de Odds Ratio (OR) con IC al 95%. RESULTADOS: La regresión logística cruda mostró que los trabajadores por turnos realizaban menor actividad física (OR=0,22; IC 95%=0,14-0,35; p<0,001) y tenían niveles de colesterol HDL más bajos (OR=2,1; IC 95%=1,2-3,8; p<0,05), así como mayor tasa de hipertrigliceridemia (OR=2,05; IC 95%=1,3-3,2; p<0,01) e hiperuricemia (OR=2,7; IC 95%=0,9-2,7; p<0,001). En la regresión logística ajustada por edad, sexo, consumo de tabaco, actividad física y turnicidad, sólo se mantuvo la asociación entre trabajo por turnos e hiperuricemia (OR=2,25; IC 95%=1,1-4,6; p<0,05), así como con menor actividad física moderada/alta (OR=0,19; IC 95%=0,12-0,31; p<0,001). CONCLUSIONES: No se encuentra asociación entre turnicidad y un mayor nivel de tabaquismo o un mayor riesgo cardiovascular. Sí se evidencia asociación con niveles de ácido úrico altos y menor actividad física moderada/alta.

A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries.

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration.

Evolution of Experimental Models in the Study of Glioblastoma: Toward Finding Efficient Treatments.

Glioblastoma (GBM) is the most common form of brain tumor characterized by its resistance to conventional therapies, including temozolomide, the most widely used chemotherapeutic agent in the treatment of GBM. Within the tumor, the presence of glioma stem cells (GSC) seems to be the reason for drug resistance. The discovery of GSC has boosted the search for new experimental models to study GBM, which allow the development of new GBM treatments targeting these cells. In here, we describe different strategies currently in use to study GBM. Initial GBM investigations were focused in the development of xenograft assays. Thereafter, techniques advanced to dissociate tumor cells into single-cell suspensions, which generate aggregates referred to as neurospheres, thus facilitating their selective expansion. Concomitantly, the finding of genes involved in the initiation and progression of GBM tumors, led to the generation of mice models for the GBM. The latest advances have been the use of GBM organoids or 3D-bioprinted mini-brains. 3D bio-printing mimics tissue cytoarchitecture by combining different types of cells interacting with each other and with extracellular matrix components. These in vivo models faithfully replicate human diseases in which the effect of new drugs can easily be tested. Based on recent data from human glioblastoma, this review critically evaluates the different experimental models used in the study of GB, including cell cultures, mouse models, brain organoids, and 3D bioprinting focusing in the advantages and disadvantages of each approach to understand the mechanisms involved in the progression and treatment response of this devastating disease.

Hiperuricemia y menor actividad física en trabajadores a turnos: estudio transversal en una industria química española / Hyperuricemia in shift workers: a cross-sectional study in a spanish chemical factory

FUNDAMENTOS: Las conclusiones de las investigaciones sobre turnicidad y factores de riesgo cardiovascular, como los que forman parte del síndrome metabólico (SMet), no son unánimes. Las distintas definiciones del SMet y el trabajo por turnos las dificultan. Nuestro objetivo fue conocer la asociación entre el trabajo por turnos y los hábitos de vida y la salud cardiovascular de los trabajadores de una industria química. MÉTODOS: Se realizó un estudio transversal analítico entre 2018 y 2019. Los datos se obtuvieron de los exámenes de salud anuales. Se seleccionaron 515 trabajadores, estableciendo una relación de 1:3 (por turnos / sin turnos). Se recogieron como variables resultado: SMet, hipertensión arterial, obesidad, adiposidad abdominal y alteraciones bioquímicas (glucosa, colesterol total, colesterol HDL, triglicéridos y ácido úrico). Las variables explicativas fueron: edad, sexo, consumo de tabaco, actividad física y turnicidad. Aparte de los descriptivos habituales, se realizó una regresión logística bivariada cruda y otra ajustada, determinando valores de Odds Ratio (OR) con IC al 95%. RESULTADOS: La regresión logística cruda mostró que los trabajadores por turnos realizaban menor actividad física (OR=0,22; IC 95%=0,14-0,35; p < 0,001) y tenían niveles de colesterol HDL más bajos (OR=2,1; IC 95%=1,2-3,8; p < 0,05), así como mayor tasa de hipertrigliceridemia (OR=2,05; IC 95%=1,3-3,2; p < 0,01) e hi-peruricemia (OR=2,7; IC 95%=0,92,7; p < 0,001). En la regresión logística ajustada por edad, sexo, consumo de tabaco, actividad física y turnicidad, sólo se mantuvo la asociación entre trabajo por turnos e hiperuricemia (OR=2,25; IC 95%=1,1-4,6; p < 0,05), así como con menor actividad física moderada/alta (OR=0,19; IC 95%=0,12-0,31; p < 0,001). CONCLUSIONES: No se encuentra asociación entre turnicidad y un mayor nivel de tabaquismo o un mayor riesgo cardiovascular. Sí se evidencia asociación con niveles de ácido úrico altos y menor actividad física moderada/alta

BACKGROUND: There is no clear consensus over the findings of research into shift work and cardiovascular risk factors, such as those present in the metabolic syndrome (MetS). This is further confounded by the varying definitions of MetS and shift work. Our objective was to learn about the link between shift work, lifestyles and cardiovascular health in chemical factory workers. METHODS: Cross-sectional analytical study, carried out 2018-2019; data obtained from annual occupational health check-ups.515 workers chosen, with a 1:3 ratio (shifts/no shifts). Variables collected: MetS, arterial hypertension, obesity, abdominal adiposity and biochemical alterations (glucose, total cholesterol, HDL cholesterol, triglycerides and uric acid). Explanatory variables: age, gender, tobacco consumption, physical activity and shift work. Besides the usual descriptions, both non-adjusted and adjusted bivariate logistic regression were performed, producing Odds Ratio (OR) values with 95% CI. RESULTS: The non-adjusted logistic regression showed that shift workers performed less physical activity (OR=0.22; 95% CI=0.14-0.35; p < 0.001) and had lower HDL cholesterol levels (OR=2.1; 95% CI=1.2-3.8; p < 0.05), plus a higher rate of hypertriglyceridemia (OR=2.05; 95% CI=1.3-3.2; p < 0.01) and hyperuricemia (OR=2.7; 95% CI=0.9-2.7; p < 0.001). In the logistic regression adjusted for age, gender, tobacco consumption, physical activity and shift work only the prevalence of hyperuricemia was higher in shift workers (OR=2.25; 95% CI=1.1-4.6; p < 0.05), as well as with less moderate/high physical activity (OR=0.19; 95% CI=0.12-0.31; p < 0.001). CONCLUSIONS: While no link was found between shift work and increased smoking or a higher cardiovascular risk, there was evidence of an association with high uric acid levels and less moderate/high physical activity

Protein Kinase C Inhibition Mediates Neuroblast Enrichment in Mechanical Brain Injuries.

Brain injuries of different etiologies lead to irreversible neuronal loss and persisting neuronal deficits. New therapeutic strategies are emerging to compensate neuronal damage upon brain injury. Some of these strategies focus on enhancing endogenous generation of neurons from neural stem cells (NSCs) to substitute the dying neurons. However, the capacity of the injured brain to produce new neurons is limited, especially in cases of extensive injury. This reduced neurogenesis is a consequence of the effect of signaling molecules released in response to inflammation, which act on intracellular pathways, favoring gliogenesis and preventing recruitment of neuroblasts from neurogenic regions. Protein kinase C (PKC) is a family of intracellular kinases involved in several of these gliogenic signaling pathways. The aim of this study was to analyze the role of PKC isozymes in the generation of neurons from neural progenitor cells (NPCs) in vitro and in vivo in brain injuries. PKC inhibition in vitro, in cultures of NPC isolated from the subventricular zone (SVZ) of postnatal mice, leads differentiation towards a neuronal fate. This effect is not mediated by classical or atypical PKC. On the contrary, this effect is mediated by novel PKCε, which is abundantly expressed in NPC cultures under differentiation conditions. PKCε inhibition by siRNA promotes neuronal differentiation and reduces glial cell differentiation. On the contrary, inhibition of PKCθ exerts a small anti-gliogenic effect and reverts the effect of PKCε inhibition on neuronal differentiation when both siRNAs are used in combination. Interestingly, in cortical brain injuries we have found expression of almost all PKC isozymes found in vitro. Inhibition of PKC activity in this type of injuries leads to neuronal production. In conclusion, these findings show an effect of PKCε in the generation of neurons from NPC in vitro, and they highlight the role of PKC isozymes as targets to produce neurons in brain lesions.

Specific inhibition of ADAM17/TACE promotes neurogenesis in the injured motor cortex.

Brain injuries in the adult mammalian brain are accompanied by a fast neurogenic response inside neurogenic niches. However, this response does not contribute to the generation of new neurons within damaged tissues like the cerebral cortex, which are essentially non-neurogenic. This occurs because injuries create a hostile environment that favors gliogenesis. Overexpression and sequential activation of the ADAM17/TGFα/EGFR signaling cascade are crucial for the generation of this gliogenic/non-neurogenic environment. Here, we demonstrate that chronic local infusion of a general metalloprotease inhibitor in areas of traumatic cortical injury in adult mice moderately increased the number of neuroblasts around the lesion, by facilitating the survival of neuroblasts and undifferentiated progenitors, which had migrated to the perilesional area from the subventricular zone. Next, we generated a dominant-negative version of ADAM17 metalloprotease, consisting of a truncated protein containing only the pro-domain (ADAM17-Pro). Specific inhibition of ADAM17 activity by ADAM17-Pro overexpression increased the generation of new neurons in vitro. Local overexpression of ADAM17-Pro in injured cortex in vivo, mediated by lentiviral vectors, dramatically increased the number of neuroblasts observed at the lesion 14 days after injury. Those neuroblasts were able to differentiate into cholinergic and GABAergic neurons 28 days after injury. We conclude that ADAM17 is a putative target to develop new therapeutic tools for the treatment of traumatic brain injury.

ELAC (3,12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCß activation.

BACKGROUND AND PURPOSE: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation. EXPERIMENTAL APPROACH: We isolated four lathyranes from the latex of Euphorbia plants and tested their effect on postnatal NPC proliferation, using neurosphere cultures. The bioactive lathyrane ELAC (3,12-di-O-acetyl-8-O-tigloilingol) was also injected into the ventricles of adult mice to analyse its effect on adult NPC proliferation in vivo. KEY RESULTS: The lathyrane ELAC activated PKC and significantly increased postnatal NPC proliferation in vitro, particularly in synergy with FGF2. In addition ELAC stimulated proliferation of NPC, specifically affecting undifferentiated transit amplifying cells. The proliferative effect of ELAC was reversed by either the classical/novel PKC inhibitor Gö6850 or the classical PKC inhibitor Gö6976, suggesting that NPC proliferation is promoted in response to activation of classical PKCs, particularly PKCß. ELAC slightly increased the proportion of NPC expressing Sox2. The effects of ELAC disappeared upon acetylation of its C7-hydroxyl group. CONCLUSIONS AND IMPLICATIONS: We propose lathyranes like ELAC as new drug candidates to modulate adult neurogenesis through PKC activation. Functional and structural comparisons between ELAC and phorboids are included.

Altered regulation of the Spry2/Dyrk1A/PP2A triad by homocysteine impairs neural progenitor cell proliferation.

Hyperhomocysteinemia reduces neurogenesis in the adult mouse brain. Homocysteine (Hcy) inhibits postnatal neural progenitor cell (NPC) proliferation by specifically impairing the fibroblast growth factor receptor (FGFR)-Erk1/2-cyclin E signaling pathway. We demonstrate herein that the inhibition of FGFR-dependent NPC proliferation induced by Hcy is mediated by its capacity to alter the cellular methylation potential. Our results show that this alteration modified the expression pattern and activity of Sprouty2 (Spry2), a negative regulator of the above mentioned pathway. Both elevated concentrations of Hcy and methyltransferase activity inhibition induced Spry2 promoter demethylation in NPC cultures leading to a sustained upregulation of the expression of Spry2 mRNA and protein. In addition, protein levels of two kinases responsible for Spry2 activation/deactivation were altered by Hcy: Spry2 kinase Dyrk1A levels diminished while Spry2 phosphatase PP2A increased, leading to changes in the phosphorylation pattern, activity and stability of Spry2. In conclusion, Hcy inhibits NPC proliferation by indirect mechanisms involving alterations in DNA methylation, gene expression, and Spry2 function, causing FGFR signaling impairment.

12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation.

BACKGROUND: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. METHODOLOGY: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. RESULTS: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. CONCLUSIONS: This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical agents to facilitate neuronal renewal.

Glycidic components expressed in the intestinal epithelium of teratomas are similar to those presented in both tumoral and inflammatory intestinal disease / Los componentes glicídicos expresados en el epitelio intestinal de los teratomas son similares a los presentes en la enfermedad intestinal inflamatoria y tumoral

In this work we used several different lectins to determine the glycidic components that appear in the prismatic intestinal epithelium of teratomas along the development. These tumoral masses show structures derived from the three blastodermic layers and usually present transdifferentiative processes. Many authors have reported glycoproteic changes in malignant processes of the colonic epithelium, attending to many environmental influences, but the development of this kind of tumour does not appear to be influenced by these factors. The present data show that many of the glycidic components expressed in the prismatic intestinal epithelium of teratomas are very similar to those observed in this mucosa in both tumoral and inflammatory disease (AU)

En este trabajo usamos diferentes lectinas para determinar los componentes glicídicos que aparecen en el epitelio prismático intestinal de teratomas a lo largo del desarrollo. Estas masas tumorales muestran estructuras derivadas de las tres hojas blastodérmicas y normalmente presentan procesos de transdiferenciación. Muchos autores han referido cambios glicoproteicos en procesos malignos del epitelio del colon atendiendo a muchas influencias ambientales, pero el desarrollo de esta clase de tumores no parece estar influenciado por estos factores. Los datos presentes muestran que muchos de los componentes glicídicos expresados en el epitelio intestinal prismático de los teratomas son muy similares a los observados en esta mucosa en la enfermedad inflamatoria y tumoral (AU)