I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

https://www.pure.ed.ac.uk/ws/files/14186931/A_Perivascular_Origin_for_Mesenchymal_Stem_Cells_in_Multiple_Human_Organs.pdf

A perivascular origin for mesenchymal stem cells in multiple human organs

Macrophages, the most plastic cells of the haematopoietic system, are found in all tissues and show great functional diversity. They have roles in development, homeostasis, tissue repair and immunity. Although tissue macrophages are anatomically distinct from one another, and have different transcriptional profiles and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this Review, we discuss how macrophages regulate normal physiology and development, and provide several examples of their pathophysiological roles in disease. We define the 'hallmarks' of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. It is essential to understand this diversity because macrophages have emerged as important therapeutic targets in many human diseases.

/pdf/macrophage-biology-in-development-homeostasis-and-disease-2nq2u94n8n.pdf

Macrophage biology in development, homeostasis and disease

The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin(+) MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent 'mesenspheres' that can self-renew and expand in serial transplantations. Nestin(+) MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or beta3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin(+) cells and favours their osteoblastic differentiation, in vivo nestin(+) cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin(+) MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin(+) cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.

/pdf/mesenchymal-and-haematopoietic-stem-cells-form-a-unique-bone-3477057m0k.pdf

Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

Nestin expression in hair follicle stem cells

Non-human transgenic mammals are produced which have, incorporated in their genome, DNA which includes a regulatory sequence of a mammalian nestin gene, operably linked to a gene coding for a nuclear localization signal peptide fused to a marker protein or reporter protein. The regulatory sequence can include a promoter and a sequence present in the second intron of the mammalian nestin gene. Preferably, the marker protein or reporter protein is a fluorescent protein, for example a cyan fluorescent protein, modified for enhanced fluorescence. Multipotent and, in particular, neural stem and progenitor cell populations are quantitatively observed in the organs of the non-human transgenic mammal or progeny thereof. Multipotent stem and progenitor cells are isolated directly from the non-human transgenic mammal, progeny or embryo thereof, for example by FACS, without culture passages.

Non-human transgenic mammals useful for identifying and assessing neural stem/progenitor cells

down-regulation proliferation of stromal cells, c-Kit activation, and CXCL12 FGF-2 expands murine hematopoietic stem and progenitor cells via

It is generally accepted that retinal neurogenesis in mammals ceases shortly after birth and that stem/progenitor cells found in the postnatal eyes of mice and humans are in the quiescent state. In the present study, we have investigated postnatal retinal neurogenesis and its modulation by visual experience in the mouse model. Four age groups (P26, P45, P72, and P94) of transgenic mice expressing green fluorescent protein (GFP) in the retinal progenitor cells under the control of nestin regulatory elements were examined for the presence of nestin-GFP-positive proliferating progenitor cells in the retina. Contrary to the previously held belief, we found a significant number of proliferating progenitors at the retinal periphery in all age groups examined. The majority of these cells gave rise to photoreceptors as revealed by the genetic cell fate mapping experiments. The intensity of neurogenesis was declining with age, and strongly correlated with eye growth. Visual form deprivation resulted in a significant increase in the intensity of peripheral neurogenesis, which correlated strongly with the induced ocular growth. The susceptibility to both form-deprivation-induced increase in the peripheral neurogenesis and form-deprivation-induced increase in the ocular growth declined with age ceasing completely around P70, which marked the end of the critical period for the vision-dependent modulation of both ocular growth and postnatal retinal neurogenesis. Thus, neurogenesis in the peripheral retina of young mice is modulated by visual input, but only during a critical period in postnatal development.

https://biorxiv.org/content/10.1101/2021.08.30.458213v1.full.pdf

Critical period for vision-dependent modulation of postnatal retinal neurogenesis

Background: Critical periods (CP) in brain development are characterized by heightened neural plasticity in the relevant brain regions.  They are associated with changes in gene expression cascades, in particular with altered expression of genes involved in plasticity regulation, such as immediate early genes.  Here we examine the expression of the immediate early genes c-Fos and Egr1 at different stages of mouse visual cortex (VC) development. Methods: Mice 11, 25, and 50 days of age were maintained under standard light-dark conditions, deprived of light for 5 days, or deprived of light for 5 days and then exposed to light for 90 min. Their brains were analyzed at PND16 (before the onset of the CP), PND30 (during the CP) and PND55 (after the CP) to determine the changes in the number of cells expressing c-Fos and Egr1 in the binocular primary visual and primary somatosensory cortices. Results: We found highly specific induction of c-Fos expression in the primary VC in response to light. We also observed transient cross-modal activation of c-Fos in the barrel field of the primary somatosensory cortex in response to light before and during the CP; such activation disappeared after the CP. Expression of Egr1 was not induced by light in the VC before the CP, but was evident during and after the CP, although the induction was much less pronounced than that of c-Fos . Conclusions: Dynamic changes in c-Fos and Egr1 expression may reflect their contribution to the VC plasticity during the CPs of postnatal brain development.

Grigori Enikolopov

Papers

Nestin expression in hair follicle stem cells

Non-human transgenic mammals useful for identifying and assessing neural stem/progenitor cells

down-regulation proliferation of stromal cells, c-Kit activation, and CXCL12 FGF-2 expands murine hematopoietic stem and progenitor cells via

Critical period for vision-dependent modulation of postnatal retinal neurogenesis

Differential activation of c-Fos and Egr1 during development of the mouse visual cortex