Comparative anatomical distribution of neuronal calcium-binding protein (NECAB) 1 and -2 in rodent and human spinal cord

Brain Struct Funct. 2016 Sep;221(7):3803-23. doi: 10.1007/s00429-016-1191-3. Epub 2016 Feb 2.


Neuronal calcium-binding protein 1 and -2 (NECAB1/2) localize to multiple excitatory neuron populations in the mouse spinal cord. Here, we analyzed rat and human spinal cord, combining in situ hybridization and immunohistochemistry, complementing newly collated data on mouse spinal cord for direct comparisons. Necab1/2 mRNA transcripts showed complementary distribution in rodent's spinal cord. Multiple-labeling fluorescence histochemistry with neuronal phenotypic markers localized NECAB1 to a dense fiber plexus in the dorsal horn, to neurons mainly in superficial layers and to commissural interneurons in both rodent species. NECAB1-positive (+) motor neurons were only found in mice. NECAB1 distribution in the human spinal cord was similar with the addition of NECAB1-like immunoreactivity surrounding myelinated axons. NECAB2 was mainly present in excitatory synaptic boutons in the dorsal horn of all three species, and often in calbindin-D28k(+) neuronal somata. Rodent ependymal cells expressed calbindin-D28k. In humans, they instead were NECAB2(+) and/or calretinin(+). Our results reveal that the association of NECAB2 to excitatory neuronal circuits in the spinal cord is evolutionarily conserved across the mammalian species investigated so far. In contrast, NECAB1 expression is more heterogeneous. Thus, our study suggests that the phenotypic segregation of NECAB1 and -2 to respective excitatory and inhibitory spinal systems can underpin functional modalities in determining the fidelity of synaptic neurotransmission and neuronal responsiveness, and might bear translational relevance to humans.

Keywords: Calbindin-D28k; Ependymal cell; PKCγ; SST2A; VGLUT1; VGLUT2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calbindin 1 / metabolism
  • Calbindin 2 / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Eye Proteins / metabolism*
  • Glutamate Decarboxylase / metabolism
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mixed Function Oxygenases / metabolism*
  • Motor Neurons / metabolism
  • Neurons / metabolism*
  • Protein Kinase C / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Somatostatin / metabolism
  • Spinal Cord / metabolism*
  • Synaptophysin / metabolism
  • Vesicular Glutamate Transport Protein 2 / metabolism


  • CALB1 protein, human
  • CALB2 protein, human
  • Calbindin 1
  • Calbindin 2
  • Calcium-Binding Proteins
  • Eye Proteins
  • NECAB2 protein, human
  • NECAB2 protein, mouse
  • NECAB2 protein, rat
  • Necab3 protein, mouse
  • RNA, Messenger
  • Receptors, Somatostatin
  • SLC17A6 protein, human
  • Synaptophysin
  • Vesicular Glutamate Transport Protein 2
  • somatostatin receptor sst2A
  • Mixed Function Oxygenases
  • NECAB1 protein, human
  • protein kinase C gamma
  • Protein Kinase C
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1