In:
eLife, eLife Sciences Publications, Ltd, Vol. 7 ( 2018-09-04)
Abstract:
Bipolar disorder is a mental illness that affects roughly 1 in 100 people worldwide. It features periods of depression interspersed with episodes of mania – a state of delusion, heightened excitation and increased activity. Evidence suggests that changes in a brain region called the locus coeruleus contribute to bipolar disorder. Cells within this area produce a chemical called norepinephrine, whose levels increase during mania and decrease during depression. But it is unclear exactly how norepinephrine-producing cells, also known as noradrenergic cells, contribute to bipolar disorder. The answer may lie in a protein called ErbB4, which is found within the outer membrane of many noradrenergic neurons. ErbB4 is active in both the developing and adult brain, and certain people with bipolar disorder have mutations in the gene that codes for the protein. Might changes in ErbB4 disrupt the activity of noradrenergic neurons? And could these changes increase the risk of bipolar disorder? To find out, Cao, Zhang et al. deleted the gene for ErbB4 from noradrenergic neurons in the locus coeruleus of mice. The mutant mice showed mania-like behaviors: compared to normal animals, they were hyperactive, less anxious, and consumed more of a sugary solution. Treating the mice with lithium, a medication used in bipolar disorder, reversed these changes and made the rodents behave more like non-mutant animals. Further experiments revealed that noradrenergic neurons in the mutant mice showed increased spontaneous activity. These animals also had more of the chemicals noradrenaline and dopamine in the fluid circulating around their brains and spinal cords. The results thus suggest that losing ErbB4 enhances the spontaneous firing of noradrenergic neurons in the locus coeruleus. This increases release of noradrenaline and dopamine, which in turn leads to mania-like behaviors. Future research should examine whether drugs that target ErbB4 could treat mania and improve the lives of people with bipolar disorder and related conditions.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.39907.001
DOI:
10.7554/eLife.39907.002
DOI:
10.7554/eLife.39907.003
DOI:
10.7554/eLife.39907.007
DOI:
10.7554/eLife.39907.004
DOI:
10.7554/eLife.39907.005
DOI:
10.7554/eLife.39907.006
DOI:
10.7554/eLife.39907.008
DOI:
10.7554/eLife.39907.011
DOI:
10.7554/eLife.39907.009
DOI:
10.7554/eLife.39907.010
DOI:
10.7554/eLife.39907.012
DOI:
10.7554/eLife.39907.015
DOI:
10.7554/eLife.39907.013
DOI:
10.7554/eLife.39907.014
DOI:
10.7554/eLife.39907.016
DOI:
10.7554/eLife.39907.019
DOI:
10.7554/eLife.39907.017
DOI:
10.7554/eLife.39907.018
DOI:
10.7554/eLife.39907.020
DOI:
10.7554/eLife.39907.025
DOI:
10.7554/eLife.39907.021
DOI:
10.7554/eLife.39907.022
DOI:
10.7554/eLife.39907.023
DOI:
10.7554/eLife.39907.024
DOI:
10.7554/eLife.39907.026
DOI:
10.7554/eLife.39907.027
DOI:
10.7554/eLife.39907.028
DOI:
10.7554/eLife.39907.029
DOI:
10.7554/eLife.39907.030
DOI:
10.7554/eLife.39907.031
DOI:
10.7554/eLife.39907.032
DOI:
10.7554/eLife.39907.034
DOI:
10.7554/eLife.39907.035
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2018
detail.hit.zdb_id:
2687154-3
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