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Zajdel, Joanna
Publications (3 of 3) Show all publications
Zajdel, J., Zager, A., Blomqvist, A., Engblom, D. & Shionoya, K. (2019). Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation. Brain, behavior, and immunity, 77, 141-149
Open this publication in new window or tab >>Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation
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2019 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 77, p. 141-149Article in journal (Refereed) Published
Abstract [en]

Maternal care is crucial for infants and profoundly affects their responses to different kinds of stressors. Here, we examined how maternal separation affects inflammatory gene expression and the corticosterone response to an acute immune challenge induced by lipopolysaccharide (LPS; 40 µg/kg ip) in mouse pups, 8–9 days old. Maternal separation initially attenuated LPS-induced hypothalamic pro-inflammatory gene expression, but later, at 3 h after immune challenge, robustly augmented such gene expression and increased serum corticosterone levels. Providing the pups with a warm and soft object prevented the separation-induced augmented hypothalamic-pituitary-adrenal (HPA)-axis response. It also prevented the potentiated induction of some, but not all, inflammatory genes to a similar extent as did the dam. Our results show that maternal separation potentiates the inflammatory response and the resulting HPA-axis activation, which may have detrimental effects if separation is prolonged or repeated.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Lipopolysaccharide, Hypothalamus, Cytokines, Inflammation, Maternal separation, Corticosterone
National Category
Pharmacology and Toxicology Developmental Biology Medical Biotechnology Immunology
Identifiers
urn:nbn:se:liu:diva-154886 (URN)10.1016/j.bbi.2018.12.016 (DOI)30590109 (PubMedID)2-s2.0-85059128986 (Scopus ID)
Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-04-08Bibliographically approved
Zajdel, J. (2019). Interactions between the brain and the immune system in pain and inflammation. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Interactions between the brain and the immune system in pain and inflammation
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Reciprocal interactions between the nervous and immune systems have gained a lot of attention in the last two decades, especially after demonstrating that cytokine immunotherapies can induce depression and after describing the inflammatory reflex. A lot of effort has been dedicated to understanding how the signals from the immune system reach the brain and vice versa, and on their role in health and disease. However, it is not well-known which of the brain circuits, receptors and signalling molecules give rise to behavioural and affective changes induced by inflammation, such as reduced food intake and induction of negative mood. Moreover, although it is well established that early life stress leads to an increased risk of developing inflammatory diseases in adulthood, the acute effects of stress on the inflammatory response in childhood are not well described. Using mouse models of systemic and local inflammation, I studied (1) how inflammatory pain elicits negative affect, (2) if CGRPα is necessary for parabrachial-amygdaloid pathway-mediated behaviours associated with pain and inflammation, and finally, (3) what are the effects of stress on the inflammatory process during early life. The results indicate that (1) the negative affect of inflammatory pain is triggered by inhibition of serotonergic neurons of the dorsal raphe nucleus, as a result of prostaglandin E2 binding to EP3 receptors; (2) CGRPα is dispensable for most pain- and inflammation-related protective behaviours; (3) acute stress potentiates the pro-inflammatory cytokine expression after an inflammatory challenge in mouse pups. The phenomena studied here can contribute to understanding how immune system activation induces changes in mood and behaviour common for inflammation and depression.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1679
Keywords
inflammation, pain, EP3Rs, serotonin, CGRP, conditioned taste aversion, maternal separation, maternal buffering
National Category
Immunology Neurosciences
Identifiers
urn:nbn:se:liu:diva-156181 (URN)10.3384/diss.diva-156181 (DOI)978-91-7685-084-8 (ISBN)
Public defence
2019-05-10, Hasselquistsalen, Växthuset, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2019-04-08 Created: 2019-04-08 Last updated: 2019-04-11Bibliographically approved
Fritz, M., Klawonn, A., Nilsson, A., Kumar Singh, A., Zajdel, J., Wilhelms, D., . . . Engblom, D. (2016). Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice. Journal of Clinical Investigation, 126(2), 695-705
Open this publication in new window or tab >>Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice
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2016 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 126, no 2, p. 695-705Article in journal (Refereed) Published
Abstract [en]

Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type-specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E-2 (PGE(2)) synthesis. Further, we showed that inflammation-induced PGE(2) targeted EP1 receptors on striatal dopamine D1 receptor-expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE(2)-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation.

Place, publisher, year, edition, pages
AMER SOC CLINICAL INVESTIGATION INC, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126263 (URN)10.1172/JCI83844 (DOI)000370677300029 ()26690700 (PubMedID)
Note

Funding Agencies|European Research Council (ERC); Swedish Medical Research Council; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; County Council of Ostergotland; Swedish Cancer Foundation; Veterans Administration Merit award; NIH [NS33987, NS72337]

Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2019-04-29Bibliographically approved
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