scholarly journals Synaptic communication mediates the assembly of a self-organizing circuit that controls reproduction

2021 ◽  
Vol 7 (8) ◽  
pp. eabc8475
Author(s):  
M. Golan ◽  
J. Boulanger-Weill ◽  
A. Pinot ◽  
P. Fontanaud ◽  
A. Faucherre ◽  
...  
Keyword(s):  
Initial Phase ◽  
Cell Communication ◽  
Glutamatergic Synapses ◽  
Phenotypic Switch ◽  
Neuronal Ensembles ◽  
Zebrafish Larvae ◽  
Active Circuit ◽  
Gnrh Neurons ◽  
The Brain

Migration of gonadotropin-releasing hormone (GnRH) neurons from their birthplace in the nasal placode to their hypothalamic destination is critical for vertebrate reproduction and species persistence. While their migration mode as individual GnRH neurons has been extensively studied, the role of GnRH-GnRH cell communication during migration remains largely unexplored. Here, we show in awake zebrafish larvae that migrating GnRH neurons pause at the nasal-forebrain junction and form clusters that act as interhemisphere neuronal ensembles. Within the ensembles, GnRH neurons create an isolated, spontaneously active circuit that is internally wired through monosynaptic glutamatergic synapses into which newborn GnRH neurons integrate before entering the brain. This initial phase of integration drives a phenotypic switch, which is essential for GnRH neurons to properly migrate toward their hypothalamic destination. Together, these experiments reveal a critical step for reproduction, which depends on synaptic communication between migrating GnRH neurons.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

scholarly journals Role of the brain-derived neurotrophic factor at glutamatergic synapses

2008 ◽  
Vol 153 (S1) ◽  
pp. S310-S324 ◽  
Author(s):  
A L Carvalho ◽  
M V Caldeira ◽  
S D Santos ◽  
C B Duarte
Keyword(s):  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Glutamatergic Synapses ◽  
The Brain

scholarly journals Hypothalamic control of the male neonatal testosterone surge

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150115 ◽  
Author(s):  
Jenny Clarkson ◽  
Allan E. Herbison
Keyword(s):  
Preoptic Area ◽  
Neonatal Period ◽  
Perinatal Period ◽  
Neuron Activity ◽  
Specific Population ◽  
Hypothalamic Control ◽  
Gnrh Neurons ◽  
Male Specific ◽  
The Brain

Sex differences in brain neuroanatomy and neurophysiology underpin considerable physiological and behavioural differences between females and males. Sexual differentiation of the brain is regulated by testosterone secreted by the testes predominantly during embryogenesis in humans and the neonatal period in rodents. Despite huge advances in understanding how testosterone, and its metabolite oestradiol, sexually differentiate the brain, little is known about the mechanism that actually generates the male-specific neonatal testosterone surge. This review examines the evidence for the role of the hypothalamus, and particularly the gonadotropin-releasing hormone (GnRH) neurons, in generating the neonatal testosterone surge in rodents and primates. Kisspeptin–GPR54 signalling is well established as a potent and critical regulator of GnRH neuron activity during puberty and adulthood, and we argue here for an equally important role at birth in driving the male-specific neonatal testosterone surge in rodents. The presence of a male-specific population of preoptic area kisspeptin neurons that appear transiently in the perinatal period provide one possible source of kisspeptin drive to neonatal GnRH neurons in the mouse.

scholarly journals Kisspeptin and energy balance in reproduction

Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. R53-R63 ◽  
Author(s):  
Julie-Ann P De Bond ◽  
Jeremy T Smith
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Arcuate Nucleus ◽  
Reproductive Function ◽  
Neuroendocrine Regulation ◽  
Direct Role ◽  
Gnrh Neurons ◽  
The Brain ◽  
Direct Regulator

Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as isKiss1expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data fromKiss1rknockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.

scholarly journals Anti-inflammatory role of GM1 and modulatory effects of gangliosides on microglia functions

2020 ◽  
Author(s):  
Danny Galleguillos ◽  
Qian Wang ◽  
Noam Steinberg ◽  
Gaurav Shrivastava ◽  
Kamaldeep Dhami ◽  
...  
Keyword(s):  
Cell Communication ◽  
Transcriptional Response ◽  
Ganglioside Gm1 ◽  
Latex Beads ◽  
Health And Disease ◽  
Anti Inflammatory ◽  
The Brain ◽  
Brain Homeostasis ◽  
Inflammatory Effect

ABSTRACTGangliosides are sialic acid-containing glycosphingolipids highly enriched in the brain. Located mainly at the plasma membrane, gangliosides play important roles in signaling and cell-to-cell communication. Lack of gangliosides causes severe early onset neurodegenerative disorders, while more subtle deficits have been reported in Parkinson’s disease and in Huntington’s disease, two misfolded protein diseases with a neuroinflammatory component. On the other hand, administration of ganglioside GM1 provides neuroprotection in both diseases and in several other models of neuronal insult. While most studies have focused on the role of endogenous gangliosides and the effects of exogenously administered GM1 in neurons, their contribution to microglia functions that are affected in neurodegenerative conditions is largely unexplored. Microglia are the immune cells of the brain and play important homeostatic functions in health and disease. In this study, we show that administration of exogenous GM1 exerts a potent anti-inflammatory effect on microglia activated with LPS, IL-1β or upon phagocytosis of latex beads. These effects are partially reproduced by L-t-PDMP, a compound that stimulates the activity of the ganglioside biosynthetic pathway, while inhibition of ganglioside synthesis with GENZ-123346 increases microglial transcriptional response to LPS. We further show that administration of GM1 increases the uptake of apoptotic bodies and latex beads by microglia, as well as microglia migration and chemotaxis in response to ATP. On the contrary, decreasing microglial ganglioside levels results in a partial impairment in both microglial activities. Finally, increasing cellular ganglioside levels results in decreased expression and secretion of microglial brain derived neurotrophic factor (BDNF). Altogether, our data suggest that gangliosides are important modulators of microglia functions that are crucial to healthy brain homeostasis, and reveal that administration of ganglioside GM1 exerts an important anti-inflammatory activity that could be exploited therapeutically.

scholarly journals The potential of nanomedicine to alter cancer stem cell dynamics: the impact of extracellular vesicles

Nanomedicine ◽  
2020 ◽  
Author(s):  
Petra Gener ◽  
Patricia Gonzalez Callejo ◽  
Joaquín Seras-Franzoso ◽  
Fernanda Andrade ◽  
Diana Rafael ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Regulatory Mechanism ◽  
Cell Communication ◽  
Metastatic Spread ◽  
Phenotypic Switch ◽  
Cell Dynamics ◽  
The Impact ◽  
New Strategies

The presence of highly resistant cancer stem cells (CSCs) within tumors as drivers of metastatic spread has been commonly accepted. Nonetheless, the likelihood of its dynamic phenotype has been strongly discussed. Importantly, intratumoral cell-to-cell communication seems to act as the main regulatory mechanism of CSC reversion. Today, new strategies for cancer treatment focusing into modulating tumor cell intercommunication and the possibility to modulate the composition of the tumor microenvironment are being explored. In this review, we summarize the literature describing the phenomenon of CSC reversion and the factors known to influence this phenotypic switch. Furthermore, we will discuss the possible role of nanomedicine toward altering this reversion, and to influence the tumor microenvironment composition and the metastatic spread of the disease.

Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain

2021 ◽  
Vol 19 ◽  
Author(s):  
Maksim Storozhuka ◽  
Andrii Cherninskyia ◽  
Oleksandr Maximyuka ◽  
Dmytro Isaeva ◽  
Oleg Krishtala
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Mammalian Brain ◽  
Glutamatergic Synapses ◽  
Cellular Processes ◽  
Acid Sensing Ion Channels ◽  
Gabaergic Synapses ◽  
Function Relationship ◽  
The Brain

: Acid-sensing ion channels (ASICs) are Na+-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1–ASIC5). Functional ASICs assembled in the plasma membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple cellular processes. ASICs are widely, but differentially expressed in the central and peripheral nervous systems. In the mammalian brain a majority of neurons express at least one ASIC subunit. Several recent reviews have summarized findings about the role of ASICs in the peripheral nervous system, particularly in nociception and proprioception, and the structure-function relationship of ASICs. However, there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons co-released with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in some pathologies such as epilepsy, mood disorders and Alzheimer's disease.

The Role of Mitochondria in the Genesis of Neuroaxonal Dystrophy in the Brains of Aging Mice

1975 ◽  
Vol 33 ◽  
pp. 372-373
Author(s):  
J.E. Johnson
Keyword(s):  
Electron Microscopy ◽  
Present Report ◽  
Light And Electron Microscopy ◽  
Dorsal Column ◽  
Neuroaxonal Dystrophy ◽  
Nucleus Gracilis ◽  
Dystrophic Axons ◽  
The Brain ◽  
Nucleus Cuneatus

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).

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