title: Comparative anatomical distribution of neuronal calcium-binding protein (NECAB) 1 and -2 in rodent and human spinal cord.
abstract: 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.
authors: Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden. mingdong.zhang@ki.se.|Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden. mingdong.zhang@ki.se.
authors: Ming-Dong
authors: MD
authors: Zhang
authors: Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.
authors: Swapnali
authors: S
authors: Barde
authors: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria.|Department of Pharmaceutical Chemistry, Medical University of Vienna, 1090, Vienna, Austria.
authors: Edit
authors: E
authors: Szodorai
authors: Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.
authors: Anna
authors: A
authors: Josephson
authors: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.
authors: Nicholas
authors: N
authors: Mitsios
authors: Department of Anatomy, Hokkaido University School of Medicine, 060-8638, Sapporo, Japan.
authors: Masahiko
authors: M
authors: Watanabe
authors: Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
authors: Johannes
authors: J
authors: Attems
authors: Department of Pharmaceutical Chemistry, Medical University of Vienna, 1090, Vienna, Austria.
authors: Gert
authors: G
authors: Lubec
authors: Institute of Neurology, Medical University of Vienna, 1090, Vienna, Austria.
authors: Gábor G
authors: GG
authors: Kovács
authors: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.|Science for Life Laboratory, Albanova University Center, Royal Institute of Technology, 10691, Stockholm, Sweden.
authors: Mathias
authors: M
authors: Uhlén
authors: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.
authors: Jan
authors: J
authors: Mulder
authors: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.|Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria.
authors: Tibor
authors: T
authors: Harkany
authors: Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.
authors: Tomas
authors: T
authors: Hökfelt
mesh_terms: D000818:Animals; D064092:Calbindin 1 / Q000378:metabolism; D064032:Calbindin 2 / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: C576498:CALB1 protein, human; C576764:CALB2 protein, human; D064092:Calbindin 1; D064032:Calbindin 2; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; C544421:NECAB2 protein, human; C438750:NECAB2 protein, mouse; C544420:NECAB2 protein, rat; C485870:Necab3 protein, mouse; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C493476:SLC17A6 protein, human; D016708:Synaptophysin; D050599:Vesicular Glutamate Transport Protein 2; C106140:somatostatin receptor sst2A; D006899:Mixed Function Oxygenases; C519811:NECAB1 protein, human; C087857:protein kinase C gamma; D011493:Protein Kinase C; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: Calbindin-D28k; Ependymal cell; PKCγ; SST2A; VGLUT1; VGLUT2