Changes in cytokine and cytokine receptor levels during postnatal development of the human dorsolateral prefrontal cortex
Copyright © 2023. Published by Elsevier Inc..
In addition to their traditional roles in immune cell communication, cytokines regulate brain development. Cytokines are known to influence neural cell generation, differentiation, maturation, and survival. However, most work on the role of cytokines in brain development investigates rodents or focuses on prenatal events. Here, we investigate how mRNA and protein levels of key cytokines and cytokine receptors change during postnatal development of the human prefrontal cortex. We find that most cytokine transcripts investigated (IL1B, IL18, IL6, TNF, IL13) are lowest at birth and increase between 1.5 and 5 years old. After 5 years old, transcriptional patterns proceeded in one of two directions: decreased expression in teens and young adults (IL1B, p = 0.002; and IL18, p = 0.004) or increased mean expression with maturation, particularly in teenagers (IL6, p = 0.004; TNF, p = 0.002; IL13, p < 0.001). In contrast, cytokine proteins tended to remain elevated after peaking significantly around 3 years of age (IL1B, p = 0.012; IL18, p = 0.026; IL6, p = 0.039; TNF, p < 0.001), with TNF protein being highest in teenagers. An mRNA-only analysis of cytokine receptor transcripts found that early developmental increases in cytokines were paralleled by increases in their ligand-binding receptor subunits, such as IL1R1 (p = 0.033) and IL6R (p < 0.001) transcripts. In contrast, cytokine receptor-associated signaling subunits, IL1RAP and IL6ST, did not change significantly between age groups. Of the two TNF receptors, the 'pro-death' TNFRSF1A and 'pro-survival' TNFRSF1B, only TNFRSF1B was significantly changed (p = 0.028), increasing first in toddlers and again in young adults. Finally, the cytokine inhibitor, IL13, was elevated first in toddlers (p = 0.006) and again in young adults (p = 0.053). While the mean expression of interleukin-1 receptor antagonist (IL1RN) was highest in toddlers, this increase was not statistically significant. The fluctuations in cytokine expression reported here support a role for increases in specific cytokines at two different stages of human cortical development. The first is during the toddler/preschool period (IL1B, IL18, and IL13), and the other occurs at adolescence/young adult maturation (IL6, TNF and IL13).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:111 |
|---|---|
| Enthalten in: |
Brain, behavior, and immunity - 111(2023) vom: 15. Juli, Seite 186-201 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sager, Rachel E H [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 12.06.2023 Date Revised 22.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bbi.2023.03.015 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM354636731 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM354636731 | ||
| 003 | DE-627 | ||
| 005 | 20231226062638.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bbi.2023.03.015 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1182.xml |
| 035 | |a (DE-627)NLM354636731 | ||
| 035 | |a (NLM)36958512 | ||
| 035 | |a (PII)S0889-1591(23)00072-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sager, Rachel E H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Changes in cytokine and cytokine receptor levels during postnatal development of the human dorsolateral prefrontal cortex |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.06.2023 | ||
| 500 | |a Date Revised 22.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Inc. | ||
| 520 | |a In addition to their traditional roles in immune cell communication, cytokines regulate brain development. Cytokines are known to influence neural cell generation, differentiation, maturation, and survival. However, most work on the role of cytokines in brain development investigates rodents or focuses on prenatal events. Here, we investigate how mRNA and protein levels of key cytokines and cytokine receptors change during postnatal development of the human prefrontal cortex. We find that most cytokine transcripts investigated (IL1B, IL18, IL6, TNF, IL13) are lowest at birth and increase between 1.5 and 5 years old. After 5 years old, transcriptional patterns proceeded in one of two directions: decreased expression in teens and young adults (IL1B, p = 0.002; and IL18, p = 0.004) or increased mean expression with maturation, particularly in teenagers (IL6, p = 0.004; TNF, p = 0.002; IL13, p < 0.001). In contrast, cytokine proteins tended to remain elevated after peaking significantly around 3 years of age (IL1B, p = 0.012; IL18, p = 0.026; IL6, p = 0.039; TNF, p < 0.001), with TNF protein being highest in teenagers. An mRNA-only analysis of cytokine receptor transcripts found that early developmental increases in cytokines were paralleled by increases in their ligand-binding receptor subunits, such as IL1R1 (p = 0.033) and IL6R (p < 0.001) transcripts. In contrast, cytokine receptor-associated signaling subunits, IL1RAP and IL6ST, did not change significantly between age groups. Of the two TNF receptors, the 'pro-death' TNFRSF1A and 'pro-survival' TNFRSF1B, only TNFRSF1B was significantly changed (p = 0.028), increasing first in toddlers and again in young adults. Finally, the cytokine inhibitor, IL13, was elevated first in toddlers (p = 0.006) and again in young adults (p = 0.053). While the mean expression of interleukin-1 receptor antagonist (IL1RN) was highest in toddlers, this increase was not statistically significant. The fluctuations in cytokine expression reported here support a role for increases in specific cytokines at two different stages of human cortical development. The first is during the toddler/preschool period (IL1B, IL18, and IL13), and the other occurs at adolescence/young adult maturation (IL6, TNF and IL13) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Adolescence | |
| 650 | 4 | |a BA46 | |
| 650 | 4 | |a Complement | |
| 650 | 4 | |a IL18 | |
| 650 | 4 | |a IL1B | |
| 650 | 4 | |a IL6 | |
| 650 | 4 | |a TNF | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Receptors, Cytokine |2 NLM | |
| 650 | 7 | |a Interleukin-13 |2 NLM | |
| 650 | 7 | |a Interleukin-18 |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Walker, Adam K |e verfasserin |4 aut | |
| 700 | 1 | |a Middleton, Frank A |e verfasserin |4 aut | |
| 700 | 1 | |a Robinson, Kate |e verfasserin |4 aut | |
| 700 | 1 | |a Webster, Maree J |e verfasserin |4 aut | |
| 700 | 1 | |a Gentile, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Ma-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Shannon Weickert, Cynthia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Brain, behavior, and immunity |d 1992 |g 111(2023) vom: 15. Juli, Seite 186-201 |w (DE-627)NLM012962538 |x 1090-2139 |7 nnns |
| 773 | 1 | 8 | |g volume:111 |g year:2023 |g day:15 |g month:07 |g pages:186-201 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbi.2023.03.015 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 111 |j 2023 |b 15 |c 07 |h 186-201 | ||