Expression of PON2 isoforms varies among brain regions in male and female African green monkeys

2022 ◽  
Vol 178 ◽  
pp. 215-218
Author(s):  
Sumit Jamwal ◽  
Jennifer K. Blackburn ◽  
John D. Elsworth
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kimberly F. Young ◽  
Rebeca Gardner ◽  
Victoria Sariana ◽  
Susan A. Whitman ◽  
Mitchell J. Bartlett ◽  
...  

AbstractBackgroundIschemic stroke is an acquired brain injury with gender-dependent outcomes. A persistent obstacle in understanding the sex-specific neuroinflammatory contributions to ischemic brain injury is distinguishing between resident microglia and infiltrating macrophages—both phagocytes—and determining cell population-specific contributions to injury evolution and recovery processes. Our purpose was to identify microglial and macrophage populations regulated by ischemic stroke using morphology analysis and the presence of microglia transmembrane protein 119 (TMEM119). Second, we examined sex and menopause differences in microglia/macrophage cell populations after an ischemic stroke.MethodsMale and female, premenopausal and postmenopausal, mice underwent either 60 min of middle cerebral artery occlusion and 24 h of reperfusion or sham surgery. The accelerated ovarian failure model was used to model postmenopause. Brain tissue was collected to quantify the infarct area and for immunohistochemistry and western blot methods. Ionized calcium-binding adapter molecule, TMEM119, and confocal microscopy were used to analyze the microglia morphology and TMEM119 area in the ipsilateral brain regions. Western blot was used to quantify protein quantity.ResultsPost-stroke injury is increased in male and postmenopause female mice vs. premenopause female mice (p< 0.05) with differences primarily occurring in the caudal sections. After stroke, the microglia underwent a region, but not sex group, dependent transformation into less ramified cells (p< 0.0001). However, the number of phagocytic microglia was increased in distal ipsilateral regions of postmenopausal mice vs. the other sex groups (p< 0.05). The number of TMEM119-positive cells was decreased in proximity to the infarct (p< 0.0001) but without a sex group effect. Two key findings prevented distinguishing microglia from systemic macrophages. First, morphological data were not congruent with TMEM119 immunofluorescence data. Cells with severely decreased TMEM119 immunofluorescence were ramified, a distinguishing microglia characteristic. Second, whereas the TMEM119 immunofluorescence area decreased in proximity to the infarcted area, the TMEM119 protein quantity was unchanged in the ipsilateral hemisphere regions using western blot methods.ConclusionsOur findings suggest that TMEM119 is not a stable microglia marker in male and female mice in the context of ischemic stroke. Until TMEM119 function in the brain is elucidated, its use to distinguish between cell populations following brain injury with cell infiltration is cautioned.


2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.


1997 ◽  
Vol 42 (6) ◽  
pp. 463-467 ◽  
Author(s):  
Dave Gayle ◽  
Sergey E. Ilyin ◽  
Carlos R. Plata-Salamán

1997 ◽  
Vol 43 (2) ◽  
pp. 173-178 ◽  
Author(s):  
Francisco Molina-Holgado ◽  
Francisco J. Alvarez ◽  
Isabel Gonzalez ◽  
Maria T. Antonio ◽  
Maria L. Leret

Author(s):  
Nada Chaari ◽  
Hatice Camgöz Akdağ ◽  
Islem Rekik

Abstract The estimation of a connectional brain template (CBT) integrating a population of brain networks while capturing shared and differential connectional patterns across individuals remains unexplored in gender fingerprinting. This paper presents the first study to estimate gender-specific CBTs using multi-view cortical morphological networks (CMNs) estimated from conventional T1-weighted magnetic resonance imaging (MRI). Specifically, each CMN view is derived from a specific cortical attribute (e.g. thickness), encoded in a network quantifying the dissimilarity in morphology between pairs of cortical brain regions. To this aim, we propose Multi-View Clustering and Fusion Network (MVCF-Net), a novel multi-view network fusion method, which can jointly identify consistent and differential clusters of multi-view datasets in order to capture simultaneously similar and distinct connectional traits of samples. Our MVCF-Net method estimates a representative and well-centered CBTs for male and female populations, independently, to eventually identify their fingerprinting regions of interest (ROIs) in four main steps. First, we perform multi-view network clustering model based on manifold optimization which groups CMNs into shared and differential clusters while preserving their alignment across views. Second, for each view, we linearly fuse CMNs belonging to each cluster, producing local CBTs. Third, for each cluster, we non-linearly integrate the local CBTs across views, producing a cluster-specific CBT. Finally, by linearly fusing the cluster-specific centers we estimate a final CBT of the input population. MVCF-Net produced the most centered and representative CBTs for male and female populations and identified the most discriminative ROIs marking gender differences. The most two gender-discriminative ROIs involved the lateral occipital cortex and pars opercularis in the left hemisphere and the middle temporal gyrus and lingual gyrus in the right hemisphere.


1997 ◽  
Vol 42 (1) ◽  
pp. 235S ◽  
Author(s):  
Patricia A. Jiménez ◽  
J. Darenberg ◽  
D. Overstreet ◽  
A.A. Mathé

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Melissa Totten ◽  
Matthew Pierce ◽  
Keith Erikson

Abstract Objectives Obesity has been linked to cognitive deficits, behavior issues, and neurodegenerative processes with trace element dysregulation as a potential trigger for their development. Sex and genetics are important factors to consider when evaluating the effects of diet-induced obesity (DIO) on neurophysiology and behavior changes. The objective of this study was to investigate sex and genetic differences on the disturbance of trace element brain biology and behavior due to DIO in male and female C57BL/6J (C57) and DBA/2J (DBA) mice. We hypothesize that alterations due to DIO will be more evident in males than females, and the DBA strain will show more resistance to DIO effects compared to the C57 strain. Methods Male and female C57 (n = 36) and DBA (n = 36) mice at 21 days old were randomly assigned a control fat diet (CFD) with 10% kcal fat/g or mineral-matched high fat diet (HFD) with 60% kcal fat/g for 16 weeks. Behavior tests for anxiety, cognition, and memory included open field (OF), novel object recognition (NOR), and nestlet shredding (NS). Trace elements iron (Fe), copper (Cu), and manganese (Mn) were measured using graphite furnace atomic absorption spectroscopy in five brain regions. Statistical analysis was conducted using factorial ANOVA and repeated measures ANOVA. Results After 16 weeks, both strains fed the HFD were confirmed obese by body mass comparison (P < 0.001). A statistically significant interaction between diet and sex was observed for C57 mice in the OF evaluation of center time (P = 0.019), with obese females exhibiting more anxiety. Differences in NS due to DIO were found in male C57 mice only (P = 0.008). NOR performance was similar for all mice. There was a statistically significant diet by sex interaction for Fe in the striatum (P = 0.032) with opposite trends by sex. Diet by strain interactions were observed for Cu in the cortex and hippocampus, and for Mn in the thalamus. Conclusions Male and female mice exhibit different behavior patterns and trace element distribution in the brain due to DIO, with more pronounced effects in the C57 strain compared to the DBA strain. Based on these findings, sex and genetics are important influences to consider when studying the consequences of obesity. Funding Sources UNCG Health and Human Sciences Research Grant and Faculty First Award.


2020 ◽  
pp. 1-8
Author(s):  
Bo Ning ◽  
Gongbo Guo ◽  
Chunming Gu ◽  
Jiadi Xu ◽  
Adnan Bibic ◽  
...  

<b><i>Background:</i></b> Parkinson’s disease (PD) is the second most common neurodegenerative disease and the most common movement disorder characterized by motor impairments resulting from midbrain dopamine neuron loss. Abnormalities in small pial arteries and arterioles, which are the primary pathways of local delivery of nutrients and oxygen in brain tissue, have been reported in many neurodegenerative diseases including PD. Mutations in LRRK2 cause genetic PD and contribute to sporadic PD. The most common PD-linked mutation LRRK2 G2019S contributes 20–47% of genetic forms of PD in Caucasian populations. The human LRRK2 G2019S transgenic mouse model displays PD-like movement impairment and was used to identify novel LRRK2 inhibitors, which provides a useful model for studying microvascular abnormalities in PD. <b><i>Objectives:</i></b> To investigate abnormalities in arteriolar cerebral blood volume (CBVa) in various brain regions using the inflow-based vascular-space occupancy (iVASO) MRI technique in LRRK2 mouse models of PD. <b><i>Methods:</i></b> Anatomical and iVASO MRI scans were performed in 5 female and 7 male nontransgenic (nTg), 3 female and 4 male wild-type (WT) LRRK2, and 5 female and 7 male G2019S-LRRK2 mice of 9 months of age. CBVa was calculated and compared in the substantia nigra (SN), olfactory cortex, and prefrontal cortex. <b><i>Results:</i></b> Compared to nTg mice, G2019S-LRRK2 mice showed decreased CBVa in the SN, but increased CBVa in the olfactory and prefrontal cortex in both male and female groups, whereas WT-LRRK2 mice showed no change in CBVa in the SN (male and female), the olfactory (female), and prefrontal (female) cortex, but a slight increase in CBVa in the olfactory and prefrontal cortex in the male group only. <b><i>Conclusions:</i></b> Alterations in the blood volume of small arteries and arterioles (CBVa) were detected in the G2019S-LRRK2 mouse model of PD. The opposite changes in CBVa in the SN and the cortex indicate that PD pathology may have differential effects in different brain regions. Our results suggest the potential value of CBVa as a marker for clinical PD studies.


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