scholarly journals Heterogeneity and developmental dynamics of LYVE-1 perivascular macrophages distribution in the mouse brain

2021 ◽  
Author(s):  
Marie Karam ◽  
Guy Malkinson ◽  
Isabelle V BRUNET
Keyword(s):  
Mouse Brain ◽  
Brain Region ◽  
Dependent Manner ◽  
Tissue Sections ◽  
Brain Physiology ◽  
Brain Functions ◽  
Perivascular Macrophages ◽  
Developmental Dynamics ◽  
The Brain ◽  
Virchow Robin Space

Brain perivascular macrophages (PVMs) belong to border-associated macrophages. PVMs are situated along blood vessels in the Virchow-Robin space and are thus found at a unique anatomical position between the endothelium and the parenchyma. Owing to their location and phagocytic capabilities, PVMs are regarded as important components that regulate various aspects of brain physiology in health and pathophysiological states. Here, used LYVE-1 to identify PVMs in the mouse brain. We used brain-tissue sections and cleared whole-brain to learn how they are distributed within the brain and across different developmental postnatal stages. We find that LYVE-1+ PVMs associate with the vasculature in a brain-region-dependent manner, where the hippocampus shows the highest density of LYVE-1+ PVMs. We show that their postnatal distribution is developmentally dynamic and peaks at P10-P20 depending on the brain region. We further demonstrate that their density is reduced in the APP/PS1 mouse model of Alzheimers Disease. In conclusion, our results show an unexpected heterogeneity and dynamics of LYVE-1+ PVMs, and support an important role for this population of PVMs during development and in regulating brain functions in steady-state and disease conditions.

scholarly journals Brain Physiology and Pathophysiology in Mental Stress

2013 ◽  
Vol 2013 ◽  
pp. 1-23 ◽  
Author(s):  
Karim Alkadhi
Keyword(s):  
Signal Transduction ◽  
Learning And Memory ◽  
Mental Stress ◽  
Negative Effects ◽  
Functional Changes ◽  
Brain Physiology ◽  
Brain Functions ◽  
Brain Structure And Function ◽  
The Impact ◽  
The Brain

Exposure to various forms of stress is a common daily occurrence in the lives of most individuals, with both positive and negative effects on brain function. The impact of stress is strongly influenced by the type and duration of the stressor. In its acute form, stress may be a necessary adaptive mechanism for survival and with only transient changes within the brain. However, severe and/or prolonged stress causes overactivation and dysregulation of the hypothalamic pituitary adrenal (HPA) axis thus inflicting detrimental changes in the brain structure and function. Therefore, chronic stress is often considered a negative modulator of the cognitive functions including the learning and memory processes. Exposure to long-lasting stress diminishes health and increases vulnerability to mental disorders. In addition, stress exacerbates functional changes associated with various brain disorders including Alzheimer’s disease and Parkinson’s disease. The primary purpose of this paper is to provide an overview for neuroscientists who are seeking a concise account of the effects of stress on learning and memory and associated signal transduction mechanisms. This review discusses chronic mental stress and its detrimental effects on various aspects of brain functions including learning and memory, synaptic plasticity, and cognition-related signaling enabled via key signal transduction molecules.

scholarly journals High-Throughput Strategy for Profiling Sequential Section With Multiplex Staining of Mouse Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Siqi Chen ◽  
Zhixiang Liu ◽  
Anan Li ◽  
Hui Gong ◽  
Ben Long ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Acute Stress ◽  
Brain Slices ◽  
Serial Sections ◽  
Whole Brain ◽  
Tissue Samples ◽  
Brain Functions ◽  
Multiple Samples ◽  
The Brain ◽  
Serial Brain

The brain modulates specific functions in its various regions. Understanding the organization of different cells in the whole brain is crucial for investigating brain functions. Previous studies have focused on several regions and have had difficulty analyzing serial tissue samples. In this study, we introduced a pipeline to acquire anatomical and histological information quickly and efficiently from serial sections. First, we developed a serial brain-slice-staining method to stain serial sections and obtained more than 98.5% of slices with high integrity. Subsequently, using the self-developed analysis software, we registered and quantified the signals of imaged sections to the Allen Mouse Brain Common Coordinate Framework, which is compatible with multimodal images and slant section planes. Finally, we validated the pipeline with immunostaining by analyzing the activity variance in the whole brain during acute stress in aging and young mice. By removing the problems resulting from repeated manual operations, this pipeline is widely applicable to serial brain slices from multiple samples in a rapid and convenient manner, which benefits to facilitate research in life sciences.

scholarly journals Changes in Fatty Acid Dietary Profile Affect the Brain–Gut Axis Functions of Healthy Young Adult Rats in a Sex-Dependent Manner

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1864
Author(s):  
Damian Jacenik ◽  
Ana Bagüés ◽  
Laura López-Gómez ◽  
Yolanda López-Tofiño ◽  
Amaia Iriondo-DeHond ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Young Adult ◽  
Standard Diet ◽  
Dependent Manner ◽  
Soy Oil ◽  
Evening Primrose ◽  
Brain Functions ◽  
Fa Composition ◽  
The Impact ◽  
The Brain

Dietary modifications, including those affecting dietary fat and its fatty acid (FA) composition, may be involved in the development of brain–gut axis disorders, with different manifestations in males and females. Our aim was to evaluate the impact of three purified diets with different FA composition on the brain–gut axis in rats of both sexes. Male and female Wistar rats fed a cereal-based standard diet from weaning were used. At young adult age (2–3 months old), animals were divided into three groups and treated each with a different refined diet for 6 weeks: a control group fed on AIN-93G diet containing 7% soy oil (SOY), and two groups fed on AIN-93G modified diets with 3.5% soy oil replaced by 3.5% coconut oil (COCO) or 3.5% evening primrose oil (EP). Different brain–gut axis parameters were evaluated during 4–6 weeks of dietary intervention. Compared with SOY diet (14% saturated FAs, and 58% polyunsaturated FAs), COCO diet (52.2% saturated FAs and 30% polyunsaturated FAs) produced no changes in brain functions and minor gastrointestinal modifications, whereas EP diet (11.1% saturated FAs and 70.56% polyunsaturated FAs) tended to decrease self-care behavior and colonic propulsion in males, and significantly increased exploratory behavior, accelerated gastrointestinal transit, and decreased cecum and fecal pellet density in females. Changes in FA composition, particularly an increase in ω-6 polyunsaturated FAs, seem to facilitate the development of brain–gut axis alterations in a sex-dependent manner, with a relatively higher risk in females.

scholarly journals Preclinical characterization of [18F]T-008, a novel PET imaging radioligand for cholesterol 24-hydroxylase

2021 ◽  
Author(s):  
Tatsuki Koike ◽  
Cristian C. Constantinescu ◽  
Shuhei Ikeda ◽  
Toshiya Nishi ◽  
Eiji Sunahara ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Pet Imaging ◽  
Rank Order ◽  
Cholesterol Homeostasis ◽  
Dependent Manner ◽  
Wild Type ◽  
In Vivo Evaluation ◽  
The Brain

Abstract Purpose Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that plays a major role in brain cholesterol homeostasis by converting cholesterol into 24S-hydroxycholesterol. The selective CH24H inhibitor soticlestat (TAK-935) is being pursued as a drug for treatment of seizures in developmental and epileptic encephalopathies. Herein, we describe the successful discovery and the preclinical validation of the novel radiolabeled CH24H ligand (3-[18F]fluoroazetidin-1-yl){1-[4-(4-fluorophenyl)pyrimidin-5-yl]piperidin-4-yl}methanone ([18F]T-008) and its tritiated analog, [3H]T-008. Methods In vitro autoradiography (ARG) studies in the CH24H wild-type (WT) and knockout (KO) mouse brain sections were conducted using [3H]T-008. PET imaging was conducted in two adult rhesus macaques using [18F]T-008. Each macaque received two test–retest baseline scans and a series of two blocking doses of soticlestat administered prior to [18F]T-008 to determine the CH24H enzyme occupancy. PET data were analyzed with Logan graphical analysis using plasma input. A Lassen plot was applied to estimate CH24H enzyme occupancy by soticlestat. Results In ARG studies, binding of [3H]T-008 was specific to CH24H in the mouse brain sections, which was not observed in CH24H KO or in wild-type mice after pretreatment with soticlestat. In rhesus PET studies, the rank order of [18F]T-008 uptake was striatum > cortical regions > cerebellum, which was consistent with CH24H distribution in the brain. Pre-blocking with soticlestat reduced the maximum uptake and increased the washout in all brain regions in a dose-dependent manner. Calculated global occupancy values for soticlestat at a dose of 0.89 mg/kg were 97–98%, indicating maximum occupancy. Conclusion The preclinical in vitro and in vivo evaluation of labeled T-008 demonstrates that [18F]T-008 is suitable for imaging CH24H in the brain and warrants further studies in humans. Graphical abstract

Applications of ion level nanosensors for neuroscience research

Nanomedicine ◽  
2020 ◽  
Vol 15 (29) ◽  
pp. 2871-2881
Author(s):  
Min Wei ◽  
Peihua Lin ◽  
Ying Chen ◽  
Ji Young Lee ◽  
Lingxiao Zhang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Membrane ◽  
Neural Activity ◽  
Cell Function ◽  
Disease Diagnosis ◽  
Brain Physiology ◽  
Brain Functions ◽  
Neuroscience Research ◽  
Ion Activities ◽  
The Brain

Ion activities are tightly associated with brain physiology, such as intracranial cell membrane potential, neural activity and neuropathology. Thus, monitoring the ion levels in the brain is of great significance in neuroscience research. Recently, nanosensors have emerged as powerful tools for monitoring brain ion levels and dynamics. With controllable structures and functions, nanosensors have been intensively used for monitoring neural activity and cell function and can be used in disease diagnosis. Here, we summarize the recent advances in the design and application of ion level nanosensors at different physiological levels, aiming to draw a connection of the interrelated intracranial ion activities. Furthermore, perspectives on the rationally designed ion level nanosensors in understanding the brain functions are highlighted.

scholarly journals Brain Region-Dependent Effects of Neuropeptide Y on Conditioned Social Fear and Anxiety-Like Behavior in Male Mice

2021 ◽  
Vol 22 (7) ◽  
pp. 3695
Author(s):  
Johannes Kornhuber ◽  
Iulia Zoicas
Keyword(s):  
Neuropeptide Y ◽  
Brain Region ◽  
Basolateral Amygdala ◽  
Dorsal Hippocampus ◽  
Brain Regions ◽  
Dependent Manner ◽  
Contextual Fear ◽  
Social Fear ◽  
Fear And Anxiety ◽  
The Brain

Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that the intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC). In the present study, we aimed to identify the brain regions that mediate these effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduces the expression of SFC-induced social fear in a brain-region-dependent manner. In more detail, NPY reduced the expression of social fear when administered into the dorsolateral septum (DLS) and central amygdala (CeA), but not when administered into the dorsal hippocampus (DH), medial amygdala (MeA) and basolateral amygdala (BLA). We also investigated whether the reduced expression of social fear might partly be due to a reduced anxiety-like behavior, and showed that NPY exerted anxiolytic-like effects when administered into the DH, DLS, CeA and BLA, but not when administered into the MeA. This study identifies the DLS and the CeA as brain regions mediating the effects of NPY on the expression of social fear and suggests that partly distinct neural circuitries mediate the effects of NPY on the expression of social fear and on anxiety-like behavior.

scholarly journals Genetic Identification of GnRH Receptor Neurons: A New Model for Studying Neural Circuits Underlying Reproductive Physiology in the Mouse Brain

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1515-1526 ◽  
Author(s):  
Shuping Wen ◽  
Iris N. Götze ◽  
Oliver Mai ◽  
Christian Schauer ◽  
Trese Leinders-Zufall ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Sexual Behaviors ◽  
Gnrh Receptor ◽  
Reproductive Physiology ◽  
Genetic Identification ◽  
Brain Areas ◽  
Brain Functions ◽  
Model Sets ◽  
Lh Rh ◽  
The Brain

Abstract GnRH signaling regulates reproductive physiology in vertebrates via the hypothalamic-pituitary-gonadal axis. In addition, GnRH signaling has been postulated to act on the brain. However, elucidating its functional role in the central nervous system has been hampered because of the difficulty in identifying direct GnRH signaling targets in live brain tissue. Here we used a binary genetic strategy to visualize GnRH receptor (GnRHR) neurons in the mouse brain and started to characterize these cells. First, we expressed different fluorescent proteins in GnRHR neurons and mapped their precise distribution throughout the brain. Remarkably, neuronal GnRHR expression was only initiated after postnatal day 16, suggesting peri- and postpubertal functions of GnRH signaling in this organ. GnRHR neurons were found in different brain areas. Many GnRHR neurons were identified in areas influencing sexual behaviors. Furthermore, GnRHR neurons were detected in brain areas that process olfactory and pheromonal cues, revealing one efferent pathway by which the neuroendocrine hypothalamus may influence the sensitivity towards chemosensory cues. Using confocal Ca2+ imaging in brain slices, we show that GnRHR neurons respond reproducibly to extracellular application of GnRH or its analog [D-TRP6]-LH-RH, indicating that these neurons express functional GnRHR. Interestingly, the duration and shape of the Ca2+ responses were similar within and different between brain areas, suggesting that GnRH signaling may differentially influence brain functions to affect reproductive success. Our new mouse model sets the stage to analyze the next level of GnRH signaling in reproductive physiology and behavior.

scholarly journals Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity

2017 ◽  
Author(s):  
Yohan Yee ◽  
Darren J. Fernandes ◽  
Leon French ◽  
Jacob Ellegood ◽  
Lindsay S. Cahill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Brain Region ◽  
Large Scale ◽  
Structural Connectivity ◽  
Brain Regions ◽  
Reticular Nucleus ◽  
Structural Covariance ◽  
The Brain ◽  
Structural Volume

AbstractAn organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings.Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed.We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the visceral area. Additionally, this pattern of explained variation differed spatially across the brain, with transcriptomic similarity playing a larger role in the cortex than subcortex, while connectivity explains structural covariance best in parts of the cortex, midbrain, and hindbrain. These results suggest that both gene expression and connectivity underlie structural volume covariance, albeit to different extents depending on brain region, and this relationship is modulated by distance.

scholarly journals Real-Time Fast Scan Cyclic Voltammetry Detection and Quantification of Exogenously Administered Melatonin in Mice Brain

2020 ◽  
Vol 8 ◽  
Author(s):  
Elisa Castagnola ◽  
Elaine M. Robbins ◽  
Kevin M. Woeppel ◽  
Moriah McGuier ◽  
Asiyeh Golabchi ◽  
...  
Keyword(s):  
Cyclic Voltammetry ◽  
Real Time ◽  
Mouse Brain ◽  
Activated Carbon Fiber ◽  
Carbon Surface ◽  
Fast Scan Cyclic Voltammetry ◽  
Brain Functions ◽  
The Brain

Melatonin (MT) has been recently considered an excellent candidate for the treatment of sleep disorders, neural injuries, and neurological diseases. To better investigate the actions of MT in various brain functions, real-time detection of MT concentrations in specific brain regions is much desired. Previously, we have demonstrated detection of exogenously administered MT in anesthetized mouse brain using square wave voltammetry (SWV). Here, for the first time, we show successful detection of exogenous MT in the brain using fast scan cyclic voltammetry (FSCV) on electrochemically pre-activated carbon fiber microelectrodes (CFEs). In vitro evaluation showed the highest sensitivity (28.1 nA/μM) and lowest detection limit (20.2 ± 4.8 nM) ever reported for MT detection at carbon surface. Additionally, an extensive CFE stability and fouling assessment demonstrated that a prolonged CFE pre-conditioning stabilizes the background, in vitro and in vivo, and provides consistent CFE sensitivity over time even in the presence of a high MT concentration. Finally, the stable in vivo background, with minimized CFE fouling, allows us to achieve a drift-free FSCV detection of exogenous administered MT in mouse brain over a period of 3 min, which is significantly longer than the duration limit (usually < 90 s) for traditional in vivo FSCV acquisition. The MT concentration and dynamics measured by FSCV are in good agreement with SWV, while microdialysis further validated the concentration range. These results demonstrated reliable MT detection using FSCV that has the potential to monitor MT in the brain over long periods of time.

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