Tau protein hyperphosphorylation in children with cerebral palsy with sleep disorders

Year 2023, , 270 - 274, 28.07.2023

Ayşe Gülşen Doğan , İhsan Çetin

https://doi.org/10.38053/acmj.1309367

Abstract

Aims: In this study, we aimed to evaluate the relationship between sleep disorder and serum tau protein levels in children with cerebral palsy.
Methods: The sample was selected among children aged 6-10 years who applied to our physical medicine and rehabilitation outpatient clinic. In order to evaluate sleep quality, the Pittsburgh Sleep Quality Index (PSQI) questionnaire was recorded by asking parents of all participants. Children with CP who had a Pittsburgh Sleep Quality Index value above 5 were determined as the sleep disorder group. We recruited 27 children with CP and sleep disorders in the first patient group (Group 1), 27 children with CP but without sleep disorders in the second group (Group 2). The third group (Group 3), which was the healthy group, included 27 children without any disease. We also recorded the age of children at diagnosis, risk factors for CP (premature, prolonged birth, etc.), CP type, gross motor function classification system (GMFCS), botox application, orthoses usage, maternal age at birth, and additional problems. We measured total tau protein (T-tau) and phosphorylated tau protein (P-tau) levels in blood samples through a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). The correlation between tau protein and PSQI values was examined.
Results: Maternal age (p=0.001), gross motor function classification system (GMFCS) (p=0.001), and pittsburgh sleep quality index (PSQI) (p=0.001) were significantly higher in the group with sleep disorders. There was a statistically significant difference between the groups in terms of serum T-Tau and P-tau protein levels (T-tau p=0.003, P-tau p=0.004). In the group sleep disorders, PSQI was significantly correlated with T-tau (r=0.499) and P-tau (r=0.473).
Conclusion: This study shows that tau protein levels are higher in CP patients with sleep disorders than in participants without sleep disorders. In the correlation analyzes, a positive and significant correlation was observed between PSQI values and T-tau and P-tau in sleep disorders groups, and no correlation was found in without sleep disorders.

Keywords

Cerebral palsy, Tau protein, phosphorylated tau protein, sleep disorders

Tau protein hyperphosphorylation in children with cerebral palsy with sleep disorders

Abstract

Amaç: Bu çalışmada serebral palsili çocuklarda uyku bozukluğu ile serum tau protein düzeyleri arasındaki ilişkiyi değerlendirmeyi amaçladık.
Gereç ve yöntem: Örneklem, fizik tedavi ve rehabilitasyon polikliniğimize başvuran 6-10 yaş arası çocuklardan seçildi. Uyku kalitesini değerlendirmek için tüm katılımcıların ebeveynlerine sorarak Pittsburgh Uyku Kalitesi İndeksi (PUKİ) anketi kaydedildi. Pittsburgh Uyku Kalitesi İndeksi değeri 5'in üzerinde olan SP'li çocuklar uyku bozukluğu grubu olarak belirlendi ve birinci hasta grubuna (Grup 1) SP'li 27 çocuk, ikinci gruba (Grup 2) uyku bozukluğu olmayan SP'li 27 çocuk alındı. Sağlıklı grup olan üçüncü grup (Grup 3) ise herhangi bir hastalığı olmayan 27 çocuktan oluşmaktadır. Çocukların tanı yaşı, SP için risk faktörleri (erken, uzamış doğum vb.), SP tipi, kaba motor fonksiyon sınıflandırma sistemi (GMFCS), botoks uygulaması, ortez kullanımı, annenin doğum yaşı ve ek sorunları da kaydedildi. . Kan örneklerinde toplam tau proteini (T-tau) ve fosforile edilmiş tau proteini (P-tau) seviyelerini bir çift antikor sandviç enzim bağlantılı immünosorbent tahlili (ELISA) aracılığıyla ölçtük. Tau proteini ile PSQI değerleri arasındaki korelasyon incelendi.
Bulgular: Bulgular spastik SP'nin uyku bozukluğu olan grupta anlamlı olarak daha fazla olduğunu gösterdi (p=0.001). Anne yaşı (p=0,001), kaba motor fonksiyon sınıflama sistemi (GMFCS) (p=0,001) ve pittsburgh uyku kalitesi indeksi (PSQI) (p=0,001) uyku bozukluğu olan grupta anlamlı olarak yüksekti. Serum T-Tau ve P-tau protein düzeyleri açısından gruplar arasında istatistiksel olarak anlamlı fark vardı (T-tau p=0,003, P-tau p=0,004). Uyku bozuklukları grubunda PSQI, T-tau (r = 0.499) ve P-tau (r = 0.473) ile anlamlı şekilde ilişkiliydi.
Sonuç: Bu çalışma uyku bozukluğu olan SP hastalarında tau protein düzeylerinin uyku bozukluğu olmayan katılımcılara göre daha yüksek olduğunu göstermektedir. Korelasyon analizlerinde uyku bozukluğu gruplarında PSQI değerleri ile T-tau ve P-tau arasında pozitif ve anlamlı bir ilişki gözlenirken, uyku bozukluğu olmayan gruplarda korelasyon bulunmadı.

Keywords

serebral palsi, tau protein, hiperfosforilize tau protein, uyku bozukluğu

References

• Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D. A report: the definition and classification of cerebral palsy April. 2006. Dev Med Child Neurol Suppl. 2007;109:8-14.
• Oskoui M, Coutinho F, Dykeman J, Jetté N, Pringsheim, T. An update on the prevalence of cerebral palsy: a systematic review and meta-analysis. Dev Med Child Neurol. 2013;55:509-519.
• Shevell A, Wintermark P, Benini R, Shevell M, Oskoui M. Chorioamnionitis and cerebral palsy: lessons from a patient registry. Eur J Paediatr Neurol. 2014;18:301-307.
• MacLennan AH, Thompson SC, Gecz J. Cerebral palsy: causes, pathways, and the role of genetic variants. Am J Obstet Gynecol. 2015;213:779-788.
• Sankar C, Mundkur N. Cerebral palsy-definition, classification, etiology and early diagnosis. Indian J Pediatr. 2005;72:865-868.
• Dreier LA, Kapanci T, Lonnemann K, et al. Assessment of sleep-related problems in children with cerebral palsy using the SNAKE sleep questionnaire. Children. 2021;8:772.
• Löwing K, Gyllensvärd M, Tedroff K. Exploring sleep problems in young children with cerebral palsy—a population-based study. Eur J Paediatr Neurol. 2020;28:186-192.
• Lelis AL, Cardoso MV, Hall WA. Sleep disorders in children with cerebral palsy: an integrative review. Sleep Med Rev. 2016;30:63-71.
• Owens J. Classification and epidemiology of childhood sleep disorders. Sleep Med Clinics. 2007;2:353.
• Hampel H, Blennow K, Shaw LM, Hoessler YC, Zetterberg H, Trojanowski JQ. Total and phosphorylated tau protein as biological markers of Alzheimer’s disease. Experiment Gerontol. 2010;45:30-40.
• Liu MD, Luo P, Wang ZJ, Fei Z. Changes of serum Tau, GFAP, TNF-α and malonaldehyde after blast-related traumatic brain injury. Chin J Traumatol. 2014;17:317-322.
• Ojo JO, Mouzon B, Algamal M, et al. Chronic repetitive mild traumatic brain injury results in reduced cerebral blood flow, axonal injury, gliosis, and increased T-Tau and Tau oligomers. J Neuropathol Exp Neurol. 2016;75:636-655.
• Zhao J, Chen Y, Xu Y, Pi G. Effects of PTEN inhibition on the regulation of Tau phosphorylation in rat cortical neuronal injury after oxygen and glucose deprivation. Brain Inj. 2016;30:1150-1159.
• Ju YS, Ooms SJ, Sutphen C, et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-beta levels. Brain. 2017;140:2104-2111.
• Agargun M. Pittsburgh uyku kalitesi indeksinin gecerligi ve guvenirligi. Turk Psikiyatri Derg. 1996;7:107-115.
• Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy:incidence, impairments and risk factors. Disabil Rehabil. 2006;28:183-91.
• Horwood L, Li P, Mok E, Shevell M, Constantin E. A systematic review and meta‐analysis of the prevalence of sleep problems in children with cerebral palsy:how do children with cerebral palsy differ from each other and from typically developing children? Sleep Health. 2019;5:555-71
• Dutt R, Roduta‐Roberts M, Brown C. Sleep and children with cerebral palsy:a review of current evidence and environmental non‐pharmacological interventions. Children (Basel). 2015;2:78-88
• Munyumu K, Idro R, Abbo C, et al. Prevalence and factors associated with sleep disorders among children with cerebral palsy in Uganda;a cross-sectional study. BMC pediatrics. 2018;18:1-7.
• Romeo DM, Brogna C, Quintiliani M, et al. Sleep disorders in children with cerebral palsy:neurodevelopmental and behavioral correlates. Sleep Med. 2014;15:213-218.
• Sandella DE, O’Brien LM, Shank LK, Warschausky SA. Sleep and quality of life in children with cerebral palsy. Sleep Med. 2011;12:252-256.
• Kadavath H, Hofele RV, Biernat J, et al. Tau stabilizes microtubules by binding at the interface between tubulin heterodimers. Proc Natl Acad Sci USA. 2015;112:7501-6.
• Ahmadian N, Hejazi S, Mahmoudi J, Talebi M. Tau pathology of Alzheimer disease: possible role of sleep deprivation. Basic Clin Neurosci. 2018;9:307-316.
• Pluta R, Bogucka-Kocka A, Ułamek-Kozioł M, Bogucki J, Kocki J, Czuczwar SJ. Ischemic tau protein gene induction as an additional key factor driving development of Alzheimer’s phenotype changes in CA1 area of hippocampus in an ischemic model of Alzheimer’s disease. Pharmacol Rep. 2018;70:881-884.
• Cantero JL, Hita-Yañez E, Moreno-Lopez B, Portillo F, Rubio A, Avila J. Tau protein role in sleep-wake cycle. J Alzheimers Dis. 2010;21:411-421.
• Pace-Schott EF, Hobson JA. The neurobiology of sleep:genetics, cellular physiology and subcortical networks. Nat Rev Neurosci. 2002;3:591-605.
• Fuller PM, Gooley JJ, Saper CB. Neurobiology of the sleep-wake cycle:sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms. 2006;21:482-493.
• Jarzynka MJ, Passey DK, Johnson DA, et al. Microtubules modulate melatonin receptors involved in phase-shifting circadian activity rhythms: in vitro and in vivo evidence. J Pineal Res. 2009;46:161-171.
• Di Meco A, Joshi YB, Praticò D. Sleep deprivation impairs memory, tau metabolism, and synaptic integrity of a mouse model of Alzheimer’s disease with plaques and tangles. Neurobiol Aging. 2014;35:1813-1820.
• Morrone CD, Raghuraman R, Hussaini SA, Yu WH. Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer’s disease. Mol Neurodegener. 2023;18(1):27.
• Benedict C, Blennow K, Zetterberg H, Cedernaes J. Effects of acute sleep loss on diurnal plasma dynamics of CNS health biomarkers in young men. Neurology. 2020;94:e1181-e1189.
• Holth JK, Fritschi SK, Wang C, et al. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science. 2019;363:880-884.
• Lucey BP, Hicks TJ, McLeland JS, et al. Effect of sleep on overnight CSF amyloid-β kinetics. Ann Neurol. 2018;83:197-204.