Newswise \u2014 Astrocytes in the lateral hypothalamus region of the brain, an area involved in the regulation of sleep and wakefulness, play a key role in neuron activity in mice and affect their behaviour, Canadian researchers have found.<\/p>\n
Led by Ciaran Murphy-Royal of Universit\u00e9 de Montr\u00e9al\u2019s affiliated hospital research centre, the CRCHUM, the scientists detail their finding in a study published in Nature Communications.<\/p>\n
In so broadening medical science\u2019s understanding of cerebral mechanisms, the discovery could someday help in the treatment and prevention of depression in humans, the researchers say.<\/p>\n
According to the scientific literature, early-life stress leads to a five-fold increase in the risk of developing a mental-health disorder as an adult, notably causing treatment-resistant disorders.<\/p>\n
Less active, day or night<\/p>\n
As brain cells, astrocytes are sensitive to variations in the blood concentration of metabolites and, in response to changes in the blood, astrocytes can modulate the extent of their interaction with neurons, their neighbouring cells.<\/p>\n
In mice, those changes are particularly responsive to the level of corticosterone, the stress hormone in the rodents\u2019 blood.<\/p>\n
\u201cIn adult mice who experienced early-life stress, we saw abnormally high levels of corticosterone,\u201d said Murphy-Royal, a professor in UdeM\u2019s Faculty of Medicine. \u201cThe impact of stress on behaviour also differed according to sex.\u201d<\/p>\n
Notably, he said, \u201cfemales were less active at night, while males were hyperactive during the day.\u201d<\/p>\n
In people with depression who have experienced a similar type of stress, this sex differences have also been observed.<\/p>\n
Lack of maternal care<\/p>\n
Lewis R. Depaauw-Holt, the study\u2019s first author and a PhD student on Murphy-Royal\u2019s team, was able to recreate early-life stress conditions in young rodents by separating them from their mothers.<\/p>\n
Over 10 days, for four hours a day, he kept the young mice apart from their mothers. This lack of maternal care occurred during a critical period of brain development for the rodents, the equivalent of ages three to seven in human children.<\/p>\n
\u201cThe differences in activity levels between female and male mice were also seen within a group of neurons that produces neuropeptides called orexins,\u201d said Murphy-Royal.<\/p>\n
\u201cLocated in the lateral hypothalamus, these orexin neurons contribute to regulating sleep-wake cycles,\u201d he said. \u201cIn males, these neurons showed hyperactivity, while in females we saw hypoactivity.\u201d<\/p>\n
In mice that experienced early-life stress, astrocytes were smaller and had fewer branches, especially in females. These branches are essential for transmitting information to neighbouring neurons and interacting with nearby cells.<\/p>\n
\u201cIn our field of expertise, we believe that the changes in astrocyte morphology are a marker of dysfunction,\u201d said Murphy-Royal. \u201cIn humans, we see these variations in diseases like Parkinson\u2019s or Alzheimer\u2019s.\u201d<\/p>\n
A single pathway?<\/p>\n
What if these changes in behaviour, neuron activity and morphology in both sexes were tied to a single stress-signalling pathway?<\/p>\n
To test their hypothesis, the CRCHUM research team deleted glucocorticoid receptors in astrocytes to which corticosterone, the stress hormone, would normally bind.<\/p>\n
\u201cWithout these receptors, neuronal activity and mouse behaviours returned to baseline similar to that of mice who did not experience early-life stress,\u201d said Murphy-Royal.<\/p>\n
\u201cAnd, even if their astrocytes didn\u2019t return to their normal size, they did regain their complexity, visible in the number of branches they use to interact with neighbouring cells.\u201d\u2009<\/p>\n
Contrary to what scientists believed until now, astrocytes are disturbed by stress before neurons are, the study reveals.<\/p>\n
In humans, the challenge of countering the effects of early-life stress will surely be more complex than in rodents, Murphy-Royal cautioned, but one thing is for sure: astrocytes could turn out to be an excellent therapeutic target for preventing depression.<\/p>\n","protected":false},"excerpt":{"rendered":"Newswise \u2014 Astrocytes in the lateral hypothalamus region of the brain, an area involved in the regulation of…\n","protected":false},"author":2,"featured_media":5093,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[6714,6715,134,527,554,6716,111,2055,139,69,6717],"class_list":{"0":"post-5092","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-astrocytesneuron-activitycorticosterone","9":"tag-behavioral-science","10":"tag-health","11":"tag-healthcare","12":"tag-mental-health","13":"tag-neuro","14":"tag-new-zealand","15":"tag-newswise","16":"tag-newzealand","17":"tag-nz","18":"tag-universite-de-montreal"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/5092","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=5092"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/5092\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/5093"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=5092"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=5092"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=5092"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}