Reduced density of functional 5-HT1A receptors in the brain, medulla and spinal cord of monoamine oxidase-A knockout mouse neonates

2006 ◽  
Vol 495 (5) ◽  
pp. 607-623 ◽  
Author(s):  
Jeanne Lanoir ◽  
Gerard Hilaire ◽  
Isabelle Seif
Keyword(s):  
Spinal Cord ◽  
Monoamine Oxidase ◽  
Knockout Mouse ◽  
Monoamine Oxidase A ◽  
Reduced Density ◽  
The Brain

scholarly journals Elevated Monoamine Oxidase A Levels in the Brain

2006 ◽  
Vol 63 (11) ◽  
pp. 1209 ◽  
Author(s):  
Jeffrey H. Meyer ◽  
Nathalie Ginovart ◽  
Anahita Boovariwala ◽  
Sandra Sagrati ◽  
Doug Hussey ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Monoamine Oxidase A ◽  
The Brain

scholarly journals Electroacupuncture improves repeated social defeat stress-elicited social avoidance and anxiety-like behaviors by reducing Lipocalin-2 in the hippocampus

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yi-Hung Chen ◽  
Sheng-Yun Xie ◽  
Chao-Wei Chen ◽  
Dah-Yuu Lu
Keyword(s):  
Monoamine Oxidase ◽  
Social Defeat ◽  
Monoamine Oxidase A ◽  
Sequencing Analysis ◽  
Social Avoidance ◽  
Lipocalin 2 ◽  
Social Defeat Stress ◽  
Astrocyte Activation ◽  
Related Disorder ◽  
The Brain

Abstract Background Post-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflammatory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors. Electroacupuncture (EA) has been proposed as a clinically useful therapy for several brain diseases. However, the potential role of EA treatment in PTSD and its molecular and cellular mechanisms has rarely been investigated. Methods We used an established preclinical social defeat stress mouse model to study whether EA treatment modulates PTSD-like symptoms and understand its underlying mechanisms. To this end, male C57BL/6 mice were subjected to repeated social defeat stress (RSDS) for 6 consecutive days to induce symptoms of PTSD and treated with EA at Baihui (GV 20) and Dazhui (GV 14) acupoints. Results The stimulation of EA, but not needle insertion at Baihui (GV 20) and Dazhui (GV 14) acupoints effectively improved PTSD-like behaviors such as, social avoidance and anxiety-like behaviors. However, EA stimulation at the bilateral Tianzong (SI11) acupoints did not affect the PTSD-like behaviors obtained by RSDS. EA stimulation also markedly inhibited astrocyte activation in both the dorsal and ventral hippocampi of RSDS-treated mice. Using next-generation sequencing analysis, our results showed that EA stimulation attenuated RSDS-enhanced lipocalin 2 expression in the hippocampus. Importantly, using double-staining immunofluorescence, we observed that the increased lipocalin 2 expression in astrocytes by RSDS was also reduced by EA stimulation. In addition, intracerebroventricular injection of mouse recombinant lipocalin 2 protein in the lateral ventricles provoked social avoidance, anxiety-like behaviors, and the activation of astrocytes in the hippocampus. Interestingly, the overexpression of lipocalin 2 in the brain also altered the expression of stress-related genes, including monoamine oxidase A, monoamine oxidase B, mineralocorticoid receptor, and glucocorticoid receptor in the hippocampus. Conclusions This study suggests that the treatment of EA at Baihui (GV 20) and Dazhui (GV 14) acupoints improves RSDS-induced social avoidance, anxiety-like behaviors, astrocyte activation, and lipocalin 2 expression. Furthermore, our findings also indicate that lipocalin 2 expression in the brain may be an important biomarker for the development of PTSD-related symptoms.

scholarly journals The Norepinephrine Metabolite DOPEGAL Confers Locus Coeruleus Tau Vulnerability and Propagation via Asparagine Endopeptidase

2019 ◽  
Author(s):  
Seong Su Kang ◽  
Xia Liu ◽  
Eun Hee Ahn ◽  
Jie Xiang ◽  
Fredric P. Manfredsson ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Locus Coeruleus ◽  
Selective Vulnerability ◽  
Monoamine Oxidase A ◽  
Noradrenergic Neurons ◽  
Tau Pathology ◽  
Intact Cells ◽  
Tau Aggregation ◽  
The Brain

AbstractAberrant Tau inclusions in the locus coeruleus (LC) are the earliest detectable Alzheimer’s disease (AD)-like neuropathology in the human brain; however, why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in disease and whether the LC might seed the stereotypical spread of Tau pathology to the rest of the brain remain unclear. Here we show that 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), which is produced exclusively in noradrenergic neurons by monoamine oxidase A (MAO-A) metabolism of norepinephrine (NE), activates asparagine endopeptidase (AEP) that cleaves Tau at residue N368 into aggregation- and propagation-prone forms, thereby leading to LC degeneration and the spread of Tau pathology. DOPEGAL triggers AEP-cleaved Tau aggregationin vitroand in intact cells, resulting in LC neurotoxicity and propagation of pathology to the forebrain. Thus, our findings reveal a novel molecular mechanism underlying the selective vulnerability of LC neurons in AD.

Regional serotonin metabolism in the brain of transgenic mice lacking monoamine oxidase A

2001 ◽  
Vol 66 (3) ◽  
pp. 423-427 ◽  
Author(s):  
Nina K. Popova ◽  
Michael A. Gilinsky ◽  
Tamara G. Amstislavskaya ◽  
Ekaterina A. Morosova ◽  
Isabelle Seif ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Transgenic Mice ◽  
Monoamine Oxidase A ◽  
Serotonin Metabolism ◽  
The Brain

scholarly journals Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-Chen Wang ◽  
Xi Wang ◽  
Jiaji Yu ◽  
Feiyang Ma ◽  
Zhe Li ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Cancer Immunotherapy ◽  
Macrophage Polarization ◽  
Monoamine Oxidase A ◽  
Tumor Associated Macrophage ◽  
Mao A ◽  
Immunosuppressive Tumor Microenvironment ◽  
The Brain ◽  
Deficient Mice ◽  
Poor Patient Survival

AbstractTargeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observe MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibit decreased TAM immunosuppressive functions corresponding with enhanced antitumor immunity. MAOI treatment induces TAM reprogramming and suppresses tumor growth in preclinical mouse syngeneic and human xenograft tumor models. Combining MAOI and anti-PD-1 treatments results in synergistic tumor suppression. Clinical data correlation studies associate high intratumoral MAOA expression with poor patient survival in a broad range of cancers. We further demonstrate that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.

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