Naslov
Developmental Expression Patterns of KCC2 and Functionally Associated Molecules in the Human Brain

Autori
Sedmak, Goran ; Jovanov-Milošević, Nataša ; Puskarjov, Martin ; Ulamec, Monika ; Krušlin, Božo ; Kaila, Kai ; Judaš, Miloš

Izvornik
Cerebral cortex (1047-3211) 26 (2015), 12; 4574-4589

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
KCC2 ; KCC3 ; NKCC1 ; Na-K ATPase ; SLC12 ; TrkB ; calpain ; calpastatin ; cation-chloride cotransporters ; human brain

Sažetak
Work on rodents demonstrated that steep upregulation of KCC2, a neuron-specific Cl- extruder of cation-chloride cotransporter (CCC) family, commences in supraspinal structures at around birth, leading to establishment of hyperpolarizing GABAergic responses. We describe spatiotemporal expression profiles of the entire CCC family in human brain. KCC2 mRNA was observed already at 10th postconceptional week (PCW) in amygdala, cerebellum, and thalamus. KCC2- immunoreactive (KCC2-ir) neurons were abundant in subplate at 18 PCW. By 25 PCW, numerous subplate and cortical plate neurons became KCC2-ir. The mRNA expression profiles of α- and β-isoforms of Na-K ATPase, which fuels cation-chloride cotransport, as well of tropomyosin receptor kinase B (TrkB), which promotes developmental upregulation of KCC2, were consistent with data from studies on rodents about their interactions with KCC2. Thus, in human brain, expression of KCC2 and its functionally associated proteins begins in early fetal period. Our work facilitates translation of results on CCC functions from animal studies to human and refutes the view that poor efficacy of anticonvulsants in the term human neonate is attributable to the lack of KCC2. We propose that perinatally low threshold for activation of Ca2+- dependent protease calpain renders neonates susceptible to downregulation of KCC2 by traumatic events, such as perinatal hypoxia ischemia.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA