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Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo.

ABSTRACT: The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1 Dbh-/-) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1 Dbh-/- mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual.

SUBMITTER: Kajimura D

PROVIDER: S-EPMC4209360 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo.

Kajimura Daisuke D Paone Riccardo R Mann J John JJ Karsenty Gerard G

Molecular metabolism 20140729 7

The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1 Dbh-/-) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1 Dbh-/- mice demonstrate an increased insulin s ...[more]

PMID: 25353004

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Project description:BACKGROUND AND PURPOSE:Poststroke hemiparesis increases the perceived challenge of walking. Perceived challenge is commonly measured by self-report, which is susceptible to measurement bias. A promising approach to objectively assess perceived challenge is measuring sympathetic nervous system (SNS) activity with skin conductance to detect the physiological stress response. We investigated the feasibility of using skin conductance measurements to detect task-related differences in the challenge posed by complex walking tasks in adults poststroke. METHODS:Adults poststroke (n = 31) and healthy young adults (n = 8) performed walking tasks including typical walking, walking in dim lighting, walking over obstacles, and dual-task walking. Measures of skin conductance and spatiotemporal gait parameters were recorded. Continuous decomposition analysis was conducted to assess changes in skin conductance level (?SCL) and skin conductance response (?SCR). A subset of participants poststroke also underwent a 12-week rehabilitation intervention. RESULTS:SNS activity measured by skin conductance (both ?SCL and ?SCR) was significantly greater for the obstacles task and dual-task walking than for typical walking in the stroke group. Participants also exhibited "cautious" gait behaviors of slower speed, shorter step length, and wider step width during the challenging tasks. Following the rehabilitation intervention, SNS activity decreased significantly for the obstacles task and dual-task walking. DISCUSSION AND CONCLUSIONS:SNS activity measured by skin conductance is a feasible approach for quantifying task-related differences in the perceived challenge of walking tasks in people poststroke. Furthermore, reduced SNS activity during walking following a rehabilitation intervention suggests a beneficial reduction in the physiological stress response evoked by complex walking tasks.Video Abstract available for more insights from the authors (See Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A234).

Dataset Information

Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo.

Publications

Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo.

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