Current Search:  Hypothalamus (x)

View All Items

  • CSV Spreadsheet
(1 - 2 of 2)
ANATOMICAL AND FUNCTIONAL ASSESSMENT OF PNMT+ NEURONS IN THE MOUSE HYPOTHALAMUS AND CEREBELLUM: POTENTIAL ROLES IN ENERGY METABOLISM AND MOTOR CONTROL
Title
ANATOMICAL AND FUNCTIONAL ASSESSMENT OF PNMT+ NEURONS IN THE MOUSE HYPOTHALAMUS AND CEREBELLUM: POTENTIAL ROLES IN ENERGY METABOLISM AND MOTOR CONTROL.
Creator
Lindo, Lake A, Ebert, Steven, University of Central Florida
Abstract / Description
Phenylethanolamine N-methyltransferase (Pnmt) is the enzyme in the catecholamine pathway responsible for converting norepinephrine to epinephrine. Pnmt is present in numerous areas; however, the scope of its expression in the mouse brain is not fully understood. A genetic mouse model was generated by the Ebert lab that exhibited the selective destruction of all Pnmt+ cells through the induction of apoptosis by Diphtheria Toxin A. Unexpected phenotypic defects arose that are characterized by...
Show morePhenylethanolamine N-methyltransferase (Pnmt) is the enzyme in the catecholamine pathway responsible for converting norepinephrine to epinephrine. Pnmt is present in numerous areas; however, the scope of its expression in the mouse brain is not fully understood. A genetic mouse model was generated by the Ebert lab that exhibited the selective destruction of all Pnmt+ cells through the induction of apoptosis by Diphtheria Toxin A. Unexpected phenotypic defects arose that are characterized by metabolic weight deficits and motor ataxia. The distribution of Pnmt+ neurons was examined throughout the hypothalamus and cerebellum to generate an anatomical map of current and historical Pnmt expression using various histochemical methods. Historical Pnmt expression appears more extensive than current expression levels at the adult stage, indicating that certain cells in the mouse brain may have experienced transient Pnmt expression. The presence of Pnmt in these regions suggests that the destruction of these neurons may play a role in the phenotypic defects observed in the ablation mouse model. Gaining a more comprehensive understanding of the potential role of Pnmt in these areas may elucidate new drug targets or novel methods to treat obesity and motor control disorders such as ataxia.
Show less
Date Issued
2018
Identifier
CFH2000547, ucf:45689
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFH2000547
Unraveling the role of Phenylethanolamine N-methyltransferase (Pnmt+) cells in-vivo
Title
Unraveling the role of Phenylethanolamine N-methyltransferase (Pnmt+) cells in-vivo.
Creator
Manja, Sanjana, Ebert, Steven, Kim, Yoon-Seong, Lambert, Stephen, University of Central Florida
Abstract / Description
Phenylethanolamine N-methyltransferase (Pnmt) is the enzyme that N-methylates norepinephrine to produce the stress hormone/neurotransmitter, epinephrine, which is abundantly expressed in adrenal glands. Developmental studies have also identified Pnmt expression in the embryonic heart and several areas of the brain, including brainstem, cerebellum, and hypothalamus. Thus, we hypothesize that selective ablation of Pnmt+ cells will have detrimental effects on cardiovascular, neuromuscular, and...
Show morePhenylethanolamine N-methyltransferase (Pnmt) is the enzyme that N-methylates norepinephrine to produce the stress hormone/neurotransmitter, epinephrine, which is abundantly expressed in adrenal glands. Developmental studies have also identified Pnmt expression in the embryonic heart and several areas of the brain, including brainstem, cerebellum, and hypothalamus. Thus, we hypothesize that selective ablation of Pnmt+ cells will have detrimental effects on cardiovascular, neuromuscular, and metabolic processes. To uncover the importance of Pnmt+ cells in vivo, we generated a novel Diphtheria Toxin A (DTA) suicide model (Pnmt+/Cre; R26+/DTA) to selectively ablate Pnmt-expressing (Pnmt+) cells in mice. Appearing normal at birth, Pnmt-Cre/DTA mice began to develop apparent cardiovascular, neurological, and metabolic impairments soon thereafter. To measure cardiac function, we performed quantitative echocardiography, electrocardiography (ECG), and blood pressure measurements. Key findings from these assessments indicated decreased left-ventricular performance, slowed atrioventricular conduction, and increased pulse pressure in the Pnmt-Cre/DTA ablation mice. These mice also showed signs of motor control deficits as early as one month, which progressively worsened with age. To assess these effects, we performed standard motor tests including hind-limb clasping, grip strength, and rotarod balance tests. Moreover, we found that the Pnmt-Cre/DTA mice ceased to gain weight shortly after puberty. The motor and metabolic deficits apparent in these animals suggested potential neurological impairments, and we thus undertook immunohistochemical staining experiments to determine the localization of Pnmt+ cells in the brain. Staining revealed Pnmt expression in the Purkinje cells of the cerebellum (motor), paraventricular nucleus of the hypothalamus (metabolic), and surprisingly extensive staining in the cerebral cortex. These results demonstrate that Pnmt+ cell contributions in the brain are much more extensive than previously thought. Overall, this work opens new pathways that will have substantial impacts on our understanding of the roles Pnmt+ cells play in normal development and disorders affecting cardiovascular, motor, and metabolic functions.
Show less
Date Issued
2019
Identifier
CFE0007495, ucf:52649
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0007495