scholarly journals Role of Apolipoprotein E in Anxiety

2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Jacob Raber
Keyword(s):  
Risk Factor ◽  
Age At Onset ◽  
Histamine Receptor ◽  
Plasma Corticosterone ◽  
Central Nucleus ◽  
Wild Type ◽  
Adult Mice ◽  
Apoe Isoforms ◽  
Dexamethasone Suppression

Anxiety is most common among Alzheimer's disease (AD) patients with an age at onset under age 65. Apolipoprotein E4 (apoE4) is a risk factor for developing AD at an earlier age and might contribute to this effect. In mice, apoE plays a role in the regulation of anxiety, which might involve histamine receptor-mediated signaling and steroidogenesis in the adrenal gland. In addition, human apoE isoforms have differential effects on anxiety in adult mice lacking apoE and probable AD patients. Compared to wild-type mice, mice lacking apoE and apoE4 mice showed pathological alterations in the central nucleus of the amygdala, which is involved in regulation of anxiety. ApoE4, but not mice lacking apoE, or apoE3 mice showed impaired dexamethasone suppression of plasma corticosterone. Understanding how apoE modulates measures of anxiety might help the developments of therapeutic targets to reduce or even prevent measures of anxiety in health and in dementing illnesses.

scholarly journals A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination

Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2255-2271 ◽  
Author(s):  
Tuancheng Feng ◽  
Rory R Sheng ◽  
Santiago Solé-Domènech ◽  
Mohammed Ullah ◽  
Xiaolai Zhou ◽  
...  
Keyword(s):  
Risk Factor ◽  
Frontotemporal Lobar Degeneration ◽  
Cathepsin D ◽  
Proteolipid Protein ◽  
Wild Type ◽  
Protein Levels ◽  
Lysosomal Protease ◽  
Precursor Cell Line ◽  
Lysosomal Membrane Protein

Abstract TMEM106B encodes a lysosomal membrane protein and was initially identified as a risk factor for frontotemporal lobar degeneration. Recently, a dominant D252N mutation in TMEM106B was shown to cause hypomyelinating leukodystrophy. However, how TMEM106B regulates myelination is still unclear. Here we show that TMEM106B is expressed and localized to the lysosome compartment in oligodendrocytes. TMEM106B deficiency in mice results in myelination defects with a significant reduction of protein levels of proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG), the membrane proteins found in the myelin sheath. The levels of many lysosome proteins are significantly decreased in the TMEM106B-deficient Oli-neu oligodendroglial precursor cell line. TMEM106B physically interacts with the lysosomal protease cathepsin D and is required to maintain proper cathepsin D levels in oligodendrocytes. Furthermore, we found that TMEM106B deficiency results in lysosome clustering in the perinuclear region and a decrease in lysosome exocytosis and cell surface PLP levels. Moreover, we found that the D252N mutation abolished lysosome enlargement and lysosome acidification induced by wild-type TMEM106B overexpression. Instead, it stimulates lysosome clustering near the nucleus as seen in TMEM106B-deficient cells. Our results support that TMEM106B regulates myelination through modulation of lysosome function in oligodendrocytes.

scholarly journals The Role of Apolipoprotein E as a Risk Factor for an Earlier Age at Onset for Machado-Joseph Disease Is Doubtful

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e111356 ◽  
Author(s):  
Qi Zhou ◽  
Wang Ni ◽  
Yi Dong ◽  
Ning Wang ◽  
Shi-Rui Gan ◽  
...  
Keyword(s):  
Risk Factor ◽  
Apolipoprotein E ◽  
Age At Onset ◽  
Machado Joseph Disease

scholarly journals Duox expression and related H2O2 measurement in mouse thyroid: onset in embryonic development and regulation by TSH in adult

2007 ◽  
Vol 192 (3) ◽  
pp. 615-626 ◽  
Author(s):  
Milutin Milenkovic ◽  
Xavier De Deken ◽  
Ling Jin ◽  
Mario De Felice ◽  
Roberto Di Lauro ◽  
...  
Keyword(s):  
Regulatory Mechanisms ◽  
Wild Type ◽  
Differentiation Markers ◽  
Hormone Synthesis ◽  
Apical Pole ◽  
Adult Mice ◽  
Tsh Stimulation ◽  
Stimulation Of ◽  
Mouse Thyroid

In the thyroid, H2O2 is produced at the apical pole of thyrocytes by one or two NADPH oxidases (NOX), Duox1/2 proteins. The onset of Duox expression was analysed by immunohistochemistry in the developing mouse thyroid in parallel with thyroglobulin (Tg) iodination and the expression of other thyroid differentiation markers. Duox proteins were found at embryonic day (E) 15.5 and were mainly localised at the apical pole of thyrocytes. Tg was detected 1 day before (E14.5) and Tg iodination was concomitant with the expression of both Duox and Na+/I− symporter (NIS; E15.5). The role of TSH in regulating Duox expression and H2O2 accumulation was evaluated in thyroids of adult mice with reduced (Tshrhyt/hyt or mice treated with thyroxine) or increased (methimazole or perchlorate treatment) TSH/Tshr activity. In mice with suppressed TSH/Tshr activity, Duox expression was only partially decreased when compared with wild-type, as observed by western blot. In Tshrhyt/hyt strain, Duox was still expressed at the apical pole and H2O2 measurements were normal. On the other hand, chronic TSH stimulation of the gland led to a decrease of H2O2 measurements without affecting Duox expression. The onset of Duox protein expression is compatible with their proposed function in thyroid hormone synthesis and it can be considered as a functional marker of the developing thyroid. However, Duox expression in adult is much less regulated by TSH than NIS and thyroperoxidase. It is not always correlated with the overall thyroid H2O2 accumulation, highlighting the importance of additional regulatory mechanisms which control either the production or H2O2 degradation.

scholarly journals Role of TRPM8 in Switching Between Fever and Hypothermia in Adult Mice During Endotoxin-Induced Inflammation

2020 ◽  
Author(s):  
Chinatsu Shiraki ◽  
Ririka Horikawa ◽  
Momoka Fujimoto ◽  
Kaho Okamoto ◽  
Erkin Kurganov ◽  
...  
Keyword(s):  
Low Dose ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
High Dose ◽  
Wild Type ◽  
Adult Mice ◽  
Severe Hypothermia ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Abstract Transient receptor potential melastatin 8 (TRPM8) functions in the sensing of noxious and innocuous colds; however, its significance in pathogen-induced thermoregulation and inflammation remains unclear. In the present study, we investigated the role of TRPM8 in the regulation of endotoxin-induced body temperature control and inflammation. The peripheral administration of low-dose LPS or zymosan generated fever in wild-type (WT) mice and hypothermia in TRPM8 knockout (KO) animals. TRPM8 KO mice exhibited severe hypothermia and sickness responses following the peripheral administration of high-dose LPS. An intracerebroventricular injection of LPS and interleukin-1ß (Il-1ß) elicited hypothermia in TRPM8 KO mice, in contrast to fever in WT animals, whereas that of prostaglandin E2 induced normal fever. Fos immunohistochemistry showed the stronger activation of hypothalamic thermoregulation-associated nuclei following the peripheral administration of low-dose LPS. Therefore, TRPM8 is necessary for switching between fever and hypothermia during endotoxin-induced inflammation.

scholarly journals β-Actin shows limited mobility and is required only for supraphysiological insulin-stimulated glucose transport in young adult soleus muscle

2018 ◽  
Vol 315 (1) ◽  
pp. E110-E125 ◽  
Author(s):  
Agnete B. Madsen ◽  
Jonas R. Knudsen ◽  
Carlos Henriquez-Olguin ◽  
Yeliz Angin ◽  
Kristien J. Zaal ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Young Adult ◽  
Actin Cytoskeleton ◽  
Glucose Transport ◽  
Wild Type ◽  
Mouse Muscle ◽  
Mature Adult ◽  
Adult Mice ◽  
Actin Isoform

Studies in skeletal muscle cell cultures suggest that the cortical actin cytoskeleton is a major requirement for insulin-stimulated glucose transport, implicating the β-actin isoform, which in many cell types is the main actin isoform. However, it is not clear that β-actin plays such a role in mature skeletal muscle. Neither dependency of glucose transport on β-actin nor actin reorganization upon glucose transport have been tested in mature muscle. To investigate the role of β-actin in fully differentiated muscle, we performed a detailed characterization of wild type and muscle-specific β-actin knockout (KO) mice. The effects of the β-actin KO were subtle; however, we confirmed the previously reported decline in running performance of β-actin KO mice compared with wild type during repeated maximal running tests. We also found insulin-stimulated glucose transport into incubated muscles reduced in soleus but not in extensor digitorum longus muscle of young adult mice. Contraction-stimulated glucose transport trended toward the same pattern, but the glucose transport phenotype disappeared in soleus muscles from mature adult mice. No genotype-related differences were found in body composition or glucose tolerance or by indirect calorimetry measurements. To evaluate β-actin mobility in mature muscle, we electroporated green fluorescent protein (GFP)-β-actin into flexor digitorum brevis muscle fibers and measured fluorescence recovery after photobleaching. GFP-β-actin showed limited unstimulated mobility and no changes after insulin stimulation. In conclusion, β-actin is not required for glucose transport regulation in mature mouse muscle under the majority of the tested conditions. Thus, our work reveals fundamental differences in the role of the cortical β-actin cytoskeleton in mature muscle compared with cell culture.

Apolipoprotein E: Cholesterol metabolism and Alzheimer’s pathology

Neuroforum ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 25-30
Author(s):  
Theresa Pohlkamp
Keyword(s):  
Risk Factor ◽  
Apolipoprotein E ◽  
Cholesterol Metabolism ◽  
Amyloid Β ◽  
Apoe Isoforms ◽  
Key Drivers ◽  
Alzheimer’S Pathology ◽  
Lipid Transporter ◽  
The Brain

AbstractAge is the greatest risk factor for Alzheimer’s disease (AD). Today, due to an increase in global life expectancy, AD-related deaths are ranked as the sixth most common cause of death. The allele isoform ɛ4 of apolipoprotein E (ApoE4) is the most important genetic risk factor for AD. Three ApoE isoforms are common in humans: ApoE2, ApoE3, and ApoE4. ApoE3 is the most frequent isoform and considered neutral with regards to AD, whereas the isoform ApoE2 is protective. Thus it is important to understand how ApoE isoforms affect amyloid-β (Aβ) and tau toxicity, the key drivers of AD pathology. Aβ and tau accumulate to form the hallmarks of AD, plaques and neurofibrillary tangles, respectively. ApoE, primarily expressed by astrocytes, is the major lipid transporter in the brain. In this review I summarize some important historic and scientific aspects of our progress in understanding the role of the cholesterol transporter ApoE in the brain, and how the isoform ApoE4 contributes to AD pathology.

scholarly journals Igf2 Deficiency Results in Delayed Lung Development at the End of Gestation

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5584-5591 ◽  
Author(s):  
Delia Silva ◽  
Maria Venihaki ◽  
Wei-Hui Guo ◽  
Mary Frances Lopez
Keyword(s):  
Fetal Lung ◽  
Plasma Corticosterone ◽  
Mrna Levels ◽  
Wild Type ◽  
Lung Maturation ◽  
Morphological Alterations ◽  
Lung Histology ◽  
Igf I ◽  
Fetal Lung Maturation

IGF-II is a polypeptide hormone with structural homology to insulin and IGF-I. IGF-II plays an important role in fetal growth as mice with targeted disruption of the IGF-II gene (Igf2) exhibit severe growth retardation. The role of IGFs in the fetal lung has been suggested by several studies, including those that have identified IGF mRNA expression, and that of their receptors and binding proteins in the lungs at different stages of development. In this study, we used mice carrying a null mutation of Igf2 (Igf2−/− mice) to determine whether the absence of IGF-II had any effect in fetal lung maturation. Our results showed that the lungs of Igf2−/− fetuses had thicker alveolar septae and poorly organized alveoli when compared with those of Igf2+/+ on d 17.5 and 18.5 of gestation. These morphological alterations may be the result of exposure to lower levels of glucocorticoids because plasma corticosterone levels were significantly lower in Igf2−/− mothers compared with wild-type controls. In support of this, fetuses from homozygous knockout matings, where mothers were treated with 15 μg/ml corticosterone, and Igf2−/− fetuses obtained from heterozygous matings had similar lung histology to those of wild-type fetuses. Finally, we found that IGF-I and SP-B mRNA levels were up-regulated in the lungs of Igf2−/− fetuses at the end of gestation. This study suggests that Igf2 plays an important role in the development of the fetal lung and may affect fetal lung maturation by regulating maternal factors, such as corticosterone levels, during pregnancy.

scholarly journals Role of Apoptosis in Rabies Viral Encephalitis: A Comparative Study in Mice, Canine, and Human Brain with a Review of Literature

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
M. S. Suja ◽  
Anita Mahadevan ◽  
S. N. Madhusudana ◽  
S. K. Shankar
Keyword(s):  
Neuronal Apoptosis ◽  
Inflammatory Cells ◽  
Postmortem Brain ◽  
Wild Type ◽  
Canine Rabies ◽  
Adult Mice ◽  
Postmortem Brain Tissue ◽  
Human Brains ◽  
Host Inflammatory Response

To evaluate the role of apoptosis in rabies encephalitis in humans and canines infected with wild-type street virus, in comparison with rodent model infected with street and laboratory passaged CVS strain, we studied postmortem brain tissue from nine humans, six canines infected with street rabies virus, and Swiss albino mice inoculated intramuscularly (IM) and intracerebrally (IC) with street and CVS strains. Encephalitis and high rabies antigen load were prominent in canine and human brains compared to rodents inoculated with street virus. Neuronal apoptosis was detectable only in sucking mice inoculated with CVS strain and minimal in street virus inoculated mice. In a time point study in suckling mice, DNA laddering was noted only terminally (7 days p.i.) following IC inoculation with CVS strain but not with street virus. In weanling and adult mice, apoptosis was restricted to inflammatory cells and absent in neurons similar to human and canine rabies-infected brains. Absence of neuronal apoptosis in wild-type rabies may facilitate intraneuronal survival and replication while apoptosis in inflammatory cells prevents elimination of the virus by abrogation of host inflammatory response.

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Endothelial Injury ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Wild Type ◽  
Type Plasminogen Activator ◽  
Pai 1

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.

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