Secretagogin expression in the vertebrate brainstem with focus on the noradrenergic system and implications for Alzheimer’s disease

Péter Zahola, János Hanics, Anna Pintér, Zoltán Máté, Anna Gáspárdy, Zsófia Hevesi, Diego Echevarria, Csaba Adori, Swapnali Barde, B. Törőcsik, Ferenc Erdélyi, Gábor Szabó, Ludwig Wagner, Gabor G. Kovacs, Tomas Hökfelt, Tibor Harkany, Alán Alpár

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Calcium-binding proteins are widely used to distinguish neuronal subsets in the brain. This study focuses on secretagogin, an EF-hand calcium sensor, to identify distinct neuronal populations in the brainstem of several vertebrate species. By using neural tube whole mounts of mouse embryos, we show that secretagogin is already expressed during the early ontogeny of brainstem noradrenaline cells. In adults, secretagogin-expressing neurons typically populate relay centres of special senses and vegetative regulatory centres of the medulla oblongata, pons and midbrain. Notably, secretagogin expression overlapped with the brainstem column of noradrenergic cell bodies, including the locus coeruleus (A6) and the A1, A5 and A7 fields. Secretagogin expression in avian, mouse, rat and human samples showed quasi-equivalent patterns, suggesting conservation throughout vertebrate phylogeny. We found reduced secretagogin expression in locus coeruleus from subjects with Alzheimer’s disease, and this reduction paralleled the loss of tyrosine hydroxylase, the enzyme rate limiting noradrenaline synthesis. Residual secretagogin immunoreactivity was confined to small submembrane domains associated with initial aberrant tau phosphorylation. In conclusion, we provide evidence that secretagogin is a useful marker to distinguish neuronal subsets in the brainstem, conserved throughout several species, and its altered expression may reflect cellular dysfunction of locus coeruleus neurons in Alzheimer’s disease.

Original languageEnglish
Pages (from-to)2061-2078
Number of pages18
JournalBrain Structure and Function
Volume224
Issue number6
DOIs
Publication statusPublished - Jul 1 2019

Keywords

  • Alzheimer’s disease
  • Calcium-binding proteins
  • Locus coeruleus
  • Norepinephrine
  • Phylogenetic conservation

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology

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    Zahola, P., Hanics, J., Pintér, A., Máté, Z., Gáspárdy, A., Hevesi, Z., Echevarria, D., Adori, C., Barde, S., Törőcsik, B., Erdélyi, F., Szabó, G., Wagner, L., Kovacs, G. G., Hökfelt, T., Harkany, T., & Alpár, A. (2019). Secretagogin expression in the vertebrate brainstem with focus on the noradrenergic system and implications for Alzheimer’s disease. Brain Structure and Function, 224(6), 2061-2078. https://doi.org/10.1007/s00429-019-01886-w