Immunohistochemical localization of calcium-binding proteins in the brainstem vestibular nuclei of the jaundiced Gunn rat.
Vestibular gaze and postural abnormalities are major sequelae of neonatal hyperbilirubinemia. The sites and cellular effects of bilirubin toxicity in the brainstem vestibular pathway are not easily detected. Since altered intracellular calcium homeostasis may play a role in neuronal cell death, we hypothesized that altered expression of calcium-binding proteins may occur in brainstem vestibular nuclei of the classic animal model of bilirubin neurotoxicity. The expression of the calcium-binding proteins calbindin-D28k and parvalbumin in the brainstem vestibular pathways and cerebellum of homozygous recessive jaundiced (jj) Gunn rats was examined by light microscopy and immunohistochemistry at 18 days postnatally and compared to the findings obtained from age-matched non-jaundiced heterozygous (Nj) littermate controls. Jaundiced animals exhibited decreased parvalbumin immunoreactivity specifically in synaptic inputs to superior, medial, and inferior vestibular nuclei, and to oculomotor and trochlear nuclei, whereas the neurons retained their normal immunoreactivity. Jaundiced animals also demonstrated a decrease in calbindin expression in the lateral vestibular nuclei and a paucity of calbindin-immunoreactive synaptic endings on the somata of Deiters' neurons. The involved regions are related to the control of the vestibulo-ocular and vestibulospinal reflexes. Decreased expression of calcium-binding proteins in brainstem vestibular neurons may relate to the vestibulo-ocular and vestibulospinal dysfunction seen with clinical kernicterus, and may provide a sensitive new way to assess bilirubin toxicity in the vestibular system.
Shaia
Wayne T
WT
Department of Otolaryngology - Head and Neck Surgery, School of Medicine, Medical College of Virginia Campus, Virginia Commonwealth University Health System, Richmond 23298-0599, USA.
Shapiro
Steven M
SM
Heller
Andrew J
AJ
Galiani
David L
DL
Sismanis
Aristides
A
Spencer
Robert F
RF
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007565:Jaundice / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism*; D051381:Rats; D011911:Rats, Gunn; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D014018:Tissue Distribution; D014726:Vestibular Nuclei / Q000378:metabolism*
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D002135:Calcium-Binding Proteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G