Neurogenesis in adult mammalian hippocampus after ischemia: rodent versus primate models

The adult mammalian hippocampus harbors neural precursor cells capable of generating glial and neuronal cells. Their existence was demonstrated in both non-primate mammals and primates including humans, and recently has attracted a significant scientific interest focused on the precursor cell potential to replace lost brain cells. Proliferation and differentiation of hippocampal progenitors are affected by brain injury and are regulated by a variety of molecular signals. Brain ischemia is a major activator of these precursors as demonstrated by experimental models in rodents and monkeys. In rodent hippocampal formation, ischemia increases neurogenesis and gliogenesis in both dentate gyrus and cornu Ammonis. In monkeys, however, ischemia was unable to trigger production of new neurons in cornu Ammonis, while in dentate gyrus postischemic progenitor cell activation was at lower levels than in rodents. Thus, rodents and primates appear to differ in their precursor cells` ability to perform neurogenesis. Unraveling the molecular machinery responsible for this interspecies discrepancy might reveal novel strategies to manipulate neural precursors for therapeutic purposes in humans.Biomedical Reviews 2005; 16: 1-11

Are there functional progenitor cells in the adult brain parenchyma?

The subventricular zone (SVZ) of the anterior horn of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus are the only regions of the adult brain that are widely recognized to contain neural progenitor cells - precursors capable of producing both neurons and glia. However, recent evidence suggests that such cells may exist also outside SVZ and SGZ, in the parenchyma of neocortex and striatum. This opens new possibilities for progenitor cell manipulation in situ with consequent development of novel progenitor-based strategies for the treatment of human neurological disease.Biomedical Reviews 2003; 14: 121-125

Fatty acids as regulators of hippocampal neurogenesis: the case of GPR40

The hippocampus of adult mammals including humans continues to generate neurons throughout life. The neural stem/progenitor cells, the cellular phenotype responsible for this regenerative capacity, are a subject of intensive research focused on the mechanisms of their regulation. Intriguing recent data implicate an unexpected molecular player in this regulation: free fatty acids. Polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids were identified to act on the pancreas via a novel receptor, named G-protein coupled receptor 40 (GPR40). However, the pancreas appears not to be the single target organ of PUFA/GPR40 actions. Very recent findings have discovered GPR40 expression in the hippocampal dentate gyrus, including its progenitor cell niche responsible for neuronal renewal throughout life. These data open a possibility that PUFA may regulate adult hippocampal neurogenesis and thus become a therapeutic tool to treat neurological disorders in humans.Biomedical Reviews 2007; 18: 69-73

Microglia are not brain macrophages?

Microglia are commonly referred to as the brain`s macrophages, which leads to confusion due to the presence of several other macrophage populations in the central nervous system. The morphological, molecular and ontological differences between these cells are subtle. They need to be clearly defined in the light of the new evidence suggesting that microglia originate not in the bone marrow, but from yolk sac, or, possibly, pericyte progenitors. Recent paradigm shift redefines the specific roles of microglia during brain development, health and disease. Microglia have emerged as key players in important events such as neurogenesis, programmed cell death, elimination of synapses and remodeling of neural circuits. These novel discoveries imply a need for a better morphological and molecular differentiation of mononuclear phagocyte populations and their subtypes in the brain. This may improve our knowledge of their specific contributions and possible pharmacological manipulation in brain health and disease

Homo diabesus: involvement of metabotrophic factors

Diabesity is a new term which refers to type 2 diabetes mellitus and obesity found in one individual, hence Homo diabesus. Previously we presented our hypothesis of metabotrophic factors (MTF), also termed metabotrophins. Onward we described Homo obesus (man obese) as a metabotrophin-deficient species. Now - as a phenotypic variety of this species - we introduce H. diabesus. Endogenous MTF are in general signaling proteins able to improve cardiovascular and metabolic homeostasis including that of lipids, glucose, energy, inflammation, angiogenesis, and cognition. Hence pharmacological manipulations of the secretion and/or signaling of MTF might bring a therapeutic benefit for H. diabesus. Here we Dance Round the hypothesis that deficit and/or dysfunction of MTF may lead to diabesity. Arguably, an updated list of MTF including nerve growth factor, brain-derived neurotrophic factor, adiponectin, humanin, irisin and other adipose- and nonadipose-derived bioactive molecules is presented. Overall this may cultivate a novel pathogenic and therapeutic thinking for cardiometabolic disease.Adipobiology 2012; 5: 45-49

Born on 19 November 1912: he, George Palade, a man who contributed so much to the progress of modern cell biology

In his 1971 paper George Palade wrote for Albert Claude, the founder of biological electron microscopic method: “Seldom has a field owed so much to a single man”. Herein, we articulate the same words for George Palade, the Teacher of many generations in cell biology research and education. Herein we focus on the paradigm shifts in the cell biology, namely the transition from light to transmission electron microscopy in studying cell protein secretion made by George Palade. Onward, we discuss on the transition from contractile to secretory phenotype of vascular smooth muscle cells initiated by Maria Daria Haust and developed by our research group. Taken together, we argue that one of the present challenges in cell biology is to cultivate secretocentric thinking and thus further focusing on how we could make secretory pathways work for the benefit of human’s health

Leydig cell-immune cell interaction: an example of neuroendocrine-immune communication in testis

In her paper "Tilings will never be the same again" Dr Kathleen L. Wishner quoted Alvin Toffler's book Future Shock written in 1970. Toffler defined "future shock" as a time phenomenon, a product of the greatly accelerated change in society. The scientific research itself is a demonstration of this accelerated change. In particular, data systematized by Davidoff et al in this volume of Biomedical Reviews indicate the change in the understanding of the nature and origin of Leydig cells of the human testis.Biomedical Reviews 1996; 6: 1-4

Zbtb20 modulates the sequential generation of neuronal layers in developing cortex

BACKGROUND: During corticogenesis, genetic programs encoded in progenitor cells at different developmental stages and inherited in postmitotic neurons specify distinct layer and area identities. Transcription factor Zbtb20 has been shown to play a role for hippocampal development but whether it is implicated in mammalian neocortical morphogenesis remains unknown. RESULTS: Here, we report that during embyogenesis transcription factor Zbtb20 has a dynamic spatio-temporal expression pattern in mitotic cortical progenitors through which it modulates the sequential generation of cortical neuronal layer identities. Zbtb20 knock out mice exhibited enhanced populations of early born L6-L4 neuronal subtypes and a dramatic reduction of the late born L3/L2 neurons. This defect was due to a temporal misbalance in the production of earlier versus later born neurons, leading to a progressive diminishing of the progenitor pool for the generation of L3-L2 neurons. Zbtb20 implements these temporal effects in part by binding to promoter of the orphan nuclear receptor CoupTF1/Nr2f1. In addition to its effects exerted in cortical progenitors, the postmitotic expression of Zbtb20 in L3/L2 neurons starting at birth may contribute to their proper differentiation and migration. CONCLUSIONS: Our findings reveal Zbtb20 as a novel temporal regulator for the generation of layer-specific neuronal identities

Metabology of Helicobacter pylori infection: role of gastrokines

Trillions of bacteria, collectively referred to as the microbiota, reside in gastrointestinal tract. Helicobacter (Campylobacter) pylori (H. pylori) is an Gram negative bacillus which infects about half of the world's population. Its causative role in gastroduodenal disease is well known. Recent studies also implicated H. pylori infection in the pathobiology of autoimmune diseases such as rheumatoid arthritis and idiopathic thrombocytopenic purpura. However, little is known about H. pylori-associated alterations in metabolic pathways and food intake as related to cardiometabolic diseases such as atherosclerosis, obesity, diabetes, and metabolic syndrome. This novel approach is conceptualized as metabology of H. pylori infection. Here we Dance Round this specific topic, with special reference to possible roles played by gastric cell-secreted molecules such as leptin, ghrelin and various cytokines, collectively designated gastrokines.Biomedical Reviews 2006; 17: 123-128

Expression of transcription factor Coup-TF1 (NR2F1) in developing occipital cortex in humans

PURPOSES: We aimed to investigate the presence, distribution and abundance of transcription factor (TF) coup-tf1 (also known as NR2F1) in the germinative zones of human telencephalon during the fetal period. This transcription factor is of significance for the normal neuronal migration and differentiation of projection neurons in the mouse forebrain.MATERIALS AND METHODS: Brain tissue samples from spontaneously aborted human fetuses aged between 12  and 28  gestational weeks (g.w.) were fixed in paraformaldehyde and histologically investigated. Sections immunostained for coup-tf1 were scanned and its expression in different zones of the occipital lobe of developing pallium was evaluated. COUP-TF1 positive cells were counted and their percentage of all DAPI-stained nuclei was calculated in order to establish the abundance of the COUP-TF1-expressing cells among the total cell population.RESULTS: COUP-TF1 expression was prominent in all investigated zones of the developing human occipital lobe at stage 17 g.w. In all zones studied, COUP-TF1 positive cells presented a relatively high fraction (~71-95 %) of the cells counted with the highest value of 95.24% in the ventricular zone.CONCLUSIONS: The present data on the location, abundance and distribution pattern of coup-tf1-expressing cells in the human occipital lobe provide information on the possibility that this TF might participate to human to corticogenesis, similarly to the mouse.