Downregulation of hypocretin/orexin after H1N1 Pandemrix vaccination of adolescent mice
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Downregulation of hypocretin/orexin after H1N1 Pandemrix vaccination of adolescent mice. / Pagh-berendtsen, Nicolai; Pavlovskyi, Artem; Flores Téllez, Daniel; Egebjerg, Christine; Kolmos, Mie Gunni; Justinussen, Jessica; Kornum, Birgitte Rahbek.
In: Sleep, Vol. 47, No. 4, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Downregulation of hypocretin/orexin after H1N1 Pandemrix vaccination of adolescent mice
AU - Pagh-berendtsen, Nicolai
AU - Pavlovskyi, Artem
AU - Flores Téllez, Daniel
AU - Egebjerg, Christine
AU - Kolmos, Mie Gunni
AU - Justinussen, Jessica
AU - Kornum, Birgitte Rahbek
PY - 2024
Y1 - 2024
N2 - Narcolepsy type 1 (NT1), characterized by the loss of hypocretin/orexin (HCRT) production in the lateral hypothalamus, has been linked to Pandemrix vaccination during the 2009 H1N1 pandemic, especially in children and adolescents. It is still unknown why this vaccination increased the risk of developing NT1. This study investigated the effects of Pandemrix vaccination during adolescence on Hcrt mRNA expression in mice. Mice received a primary vaccination (50 µL i.m.) during prepubescence and a booster vaccination during peri-adolescence. Hcrt expression was measured at three-time points after the vaccinations. Control groups included both a saline group and an undisturbed group of mice. Hcrt expression was decreased after both Pandemrix and saline injections, but 21 days after the second injection, the saline group no longer showed decreased Hcrt expression, while the Pandemrix group still exhibited a significant reduction of about 60% compared to the undisturbed control group. This finding suggests that Pandemrix vaccination during adolescence influences Hcrt expression in mice into early adulthood. The Hcrt mRNA level did not reach the low levels known to induce NT1 symptoms, instead, our finding supports the multiple-hit hypothesis of NT1 that states that several insults to the HCRT system may be needed to induce NT1 and that Pandemrix could be one such insult.
AB - Narcolepsy type 1 (NT1), characterized by the loss of hypocretin/orexin (HCRT) production in the lateral hypothalamus, has been linked to Pandemrix vaccination during the 2009 H1N1 pandemic, especially in children and adolescents. It is still unknown why this vaccination increased the risk of developing NT1. This study investigated the effects of Pandemrix vaccination during adolescence on Hcrt mRNA expression in mice. Mice received a primary vaccination (50 µL i.m.) during prepubescence and a booster vaccination during peri-adolescence. Hcrt expression was measured at three-time points after the vaccinations. Control groups included both a saline group and an undisturbed group of mice. Hcrt expression was decreased after both Pandemrix and saline injections, but 21 days after the second injection, the saline group no longer showed decreased Hcrt expression, while the Pandemrix group still exhibited a significant reduction of about 60% compared to the undisturbed control group. This finding suggests that Pandemrix vaccination during adolescence influences Hcrt expression in mice into early adulthood. The Hcrt mRNA level did not reach the low levels known to induce NT1 symptoms, instead, our finding supports the multiple-hit hypothesis of NT1 that states that several insults to the HCRT system may be needed to induce NT1 and that Pandemrix could be one such insult.
U2 - 10.1093/sleep/zsae014
DO - 10.1093/sleep/zsae014
M3 - Journal article
C2 - 38227834
VL - 47
JO - Sleep (Online)
JF - Sleep (Online)
SN - 0161-8105
IS - 4
ER -
ID: 383397441