scholarly journals Nutritional signals rapidly activate oligodendrocyte differentiation in the adult hypothalamic median eminence

2019 ◽  
Author(s):  
Sara Kohnke ◽  
Brian Lam ◽  
Sophie Buller ◽  
Chao Zhao ◽  
Danae Nuzzaci ◽  
...  

AbstractThe mediobasal hypothalamus (arcuate nucleus - ARC - and median eminence - ME -) controls energy balance, growth and fertility through its ability to integrate neuronal, nutritional and hormonal signals and coordinate the behavioural, neuroendocrine and metabolic responses required for these functions. While our understanding of the neural circuits downstream from ARC neurons is rapidly progressing, little is known about the function of other cell types. Here we describe an unexpected role for oligodendrocytes (OL) of the ME in monitoring nutritional signals. We show that refeeding following an overnight fast rapidly activates oligodendrocyte differentiation and the production of new OL in the ME specifically. No changes in myelination were measured in this time-frame. However, refeeding changed the expression of OL-derived extracellular matrix proteins decorin and tenascin-R, with consistent changes in the density of local perineuronal nets. Last, we show that OLs use mTORC1 signalling, a pathway required for OL differentiation, to survey energy and protein availability, specifically in the ME. We conclude that new oligodendrocytes formed in the ME in response to nutritional signals control the access of circulating metabolic cues to ARC interoceptive neurons.

Author(s):  
K.A. Carson ◽  
C.B. Nemeroff ◽  
M.S. Rone ◽  
J.S. Kizer ◽  
J.S. Hanker

Biochemical, physiological, pharmacological, and more recently enzyme histo- chemical data have indicated that cholinergic circuits exist in the hypothalamus. Ultrastructural correlates of these pathways such as acetylcholinesterase (AchE) positive neurons in the arcuate nucleus (ARC) and stained terminals in the median eminence (ME) have yet to be described. Initial studies in our laboratories utilizing chemical lesioning and microdissection techniques coupled with microchemical and light microscopic enzyme histo- chemical studies suggested the existence of cholinergic neurons in the ARC which project to the ME (1). Furthermore, in adult male rats with Halasz deafferentations (hypothalamic islands composed primarily of the isolated ARC and the ME) choline acetyltransferase (ChAc) activity, a good marker for cholinergic neurons, was not significantly reduced in the ME and was only somewhat reduced in the ARC (2). Treatment of neonatal rats with high doses of monosodium 1-glutamate (MSG) results in a lesion largely restricted to the neurons of the ARC.


Cell Reports ◽  
2021 ◽  
Vol 36 (2) ◽  
pp. 109362
Author(s):  
Sara Kohnke ◽  
Sophie Buller ◽  
Danae Nuzzaci ◽  
Katherine Ridley ◽  
Brian Lam ◽  
...  

Author(s):  
Femke C. C. Klouwer ◽  
Kim D. Falkenberg ◽  
Rob Ofman ◽  
Janet Koster ◽  
Démi van Gent ◽  
...  

Peroxisome biogenesis disorders within the Zellweger spectrum (PBD-ZSDs) are most frequently associated with the c.2528G>A (p.G843D) mutation in the PEX1 gene (PEX1-G843D), which results in impaired import of peroxisomal matrix proteins and, consequently, defective peroxisomal functions. A recent study suggested that treatment with autophagy inhibitors, in particular hydroxychloroquine, would be a potential therapeutic option for PBD-ZSD patients carrying the PEX1-G843D mutation. Here, we studied whether autophagy inhibition by chloroquine, hydroxychloroquine and 3-methyladenine indeed can improve peroxisomal functions in four different cell types with the PEX1-G843D mutation, including primary patient cells. Furthermore, we studied whether autophagy inhibition may be the mechanism underlying the previously reported improvement of peroxisomal functions by L-arginine in PEX1-G843D cells. In contrast to L-arginine, we observed no improvement but a worsening of peroxisomal metabolic functions and peroxisomal matrix protein import by the autophagy inhibitors, while genetic knock-down of ATG5 and NBR1 in primary patient cells resulted in only a minimal improvement. Our results do not support the use of autophagy inhibitors as potential treatment for PBD-ZSD patients, whereas L-arginine remains a therapeutically promising compound.


Author(s):  
Isaac E. Erickson ◽  
Steven C. van Veen ◽  
Swarnali Sengupta ◽  
Sydney R. Kestle ◽  
Jason A. Burdick ◽  
...  

Articular cartilage pathology is common in the aged population. Numerous studies have shown that aged chondrocytes (CHs) are inferior to juvenile CHs in their ability to proliferate and produce cartilage-specific extracellular matrix proteins, potentially limiting their use in tissue engineering applications for cartilage restoration [1,2]. Mesenchymal stem cells (MSCs) are an alternative cell type that can be expanded in vitro while maintaining their ability to differentiate into cell types comparable to articular chondrocytes. However, organismal aging also influences human MSC proliferation [3,4] and multi-potential differentiation [5], though for chondrogenesis these findings are mixed, with some suggesting that aged progenitor cells retain their chondrogenic capacity [6]. The objective of this study was to assess age related differences in donor-matched CH and MSC potential for chondrogenic repair. In addition, the effects of the chondrogenic growth factor TGF-β3 on CHs and MSCs were evaluated.


2021 ◽  
Vol 101 (1) ◽  
pp. 213-258 ◽  
Author(s):  
Rohini Kuner ◽  
Thomas Kuner

Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating, or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics, and imaging technological tools in rodent models with a view towards decoding sensory, affective, and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward, and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic, and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.


Cell Reports ◽  
2020 ◽  
Vol 31 (7) ◽  
pp. 107648 ◽  
Author(s):  
Song-Lin Ding ◽  
Zizhen Yao ◽  
Karla E. Hirokawa ◽  
Thuc Nghi Nguyen ◽  
Lucas T. Graybuck ◽  
...  
Keyword(s):  

Vision ◽  
2019 ◽  
Vol 3 (1) ◽  
pp. 4 ◽  
Author(s):  
Michael Posner ◽  
Cristopher Niell

Human neuroimaging has revealed brain networks involving frontal and parietal cortical areas as well as subcortical areas, including the superior colliculus and pulvinar, which are involved in orienting to sensory stimuli. Because accumulating evidence points to similarities between both overt and covert orienting in humans and other animals, we propose that it is now feasible, using animal models, to move beyond these large-scale networks to address the local networks and cell types that mediate orienting of attention. In this opinion piece, we discuss optogenetic and related methods for testing the pathways involved, and obstacles to carrying out such tests in rodent and monkey populations.


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