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Selection on the regulation of sympathetic nervous activity in humans and chimpanzees.

ABSTRACT: Adrenergic α2C receptor (ADRA2C) is an inhibitory modulator of the sympathetic nervous system. Knockout mice for this gene show physiological and behavioural alterations that are associated with the fight-or-flight response. There is evidence of positive selection on the regulation of this gene during chicken domestication. Here, we find that the neuronal expression of ADRA2C is lower in human and chimpanzee than in other primates. On the basis of three-dimensional chromatin structure, we identified a cis-regulatory region whose DNA sequences have been significantly accelerated in human and chimpanzee. Active histone modification marks this region in rhesus macaque but not in human and chimpanzee; instead, repressive marks are enriched in various human brain samples. This region contains two neuron-restrictive silencer factor (NRSF) binding motifs, each of which harbours a polymorphism. Our genotyping and analysis of population genome data indicate that at both polymorphic sites, the derived allele has reached fixation in humans and chimpanzees but not in bonobos, whereas only the ancestral allele is present among macaques. Our CRISPR/Cas9 genome editing and reporter assays show that both derived nucleotides repress ADRA2C, most likely by increasing NRSF binding. In addition, we detected signatures of recent positive selection for lower neuronal ADRA2C expression in humans. Our findings indicate that there has been selective pressure for enhanced sympathetic nervous activity in the evolution of humans and chimpanzees.

SUBMITTER: Lee KS

PROVIDER: S-EPMC5908061 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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).

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Selection on the regulation of sympathetic nervous activity in humans and chimpanzees.

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