A comparison of PKD2L1-expressing cerebrospinal fluid contacting neurons in spinal cords of rodents, carnivores, and primates

Xiaohe Liu, Karen Kalhøj Rich, Sohail M Nasseri, Guifa Li, Simone Hjæresen, Bente Finsen, Hansjörg Scherberger, Åsa Fex Svenningsen, Mengliang Zhang*

*Corresponding author for this work

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Cerebrospinal fluid contacting neurons (CSF-cNs) are a specific type of neurons located around the ventricles in the brain and the central canal in the spinal cord and have been demonstrated to be intrinsic sensory neurons in the central nervous system. One of the important channels responsible for the sensory function is the polycystic kidney disease 2-like 1 (PKD2L1) channel. Most of the studies concerning the distribution and function of the PKD2L1-expressing CSF-cNs in the spinal cord have previously been performed in non-mammalian vertebrates. In the present study immunohistochemistry was performed to determine the distribution of PKD2L1-immunoreactive (IR) CSF-cNs in the spinal cords of four mammalian species: mouse, rat, cat, and macaque monkey. Here, we found that PKD2L1-expressing CSF-cNs were present at all levels of the spinal cord in these animal species. Although the distribution pattern was similar across these species, differences existed. Mice and rats presented a clear PKD2L1-IR cell body labeling, whereas in cats and macaques the PKD2L1-IR cell bodies were more weakly labeled. Ectopic PKD2L1-IR neurons away from the ependymal layer were observed in all the animal species although the abundance and the detailed locations varied. The apical dendritic protrusions with ciliated fibers were clearly seen in the lumen of the central canal in all the animal species, but the sizes of protrusion bulbs were different among the species. PKD2L1-IR cell bodies/dendrites were co-expressed with doublecortin, MAP2 (microtubule-associated protein 2), and aromatic L-amino acid decarboxylase, but not with NeuN (neuronal nuclear protein), indicating their immature properties and ability to synthesize monoamine transmitters. In addition, in situ hybridization performed in rats revealed PKD2L1 mRNA expression in the cells around the central canal. Our results indicate that the intrinsic sensory neurons are conserved across non-mammalian and mammalian vertebrates. The similar morphology of the dendritic bulbs with ciliated fibers (probably representing stereocilia and kinocilia) protruding into the central canal across different animal species supports the notion that PKD2L1 is a chemo- and mechanical sensory channel that responds to mechanical stimulations and maintains homeostasis of the spinal cord. However, the differences of PKD2L1 distribution and expression between the species suggest that PKD2L1-expressing neurons may receive and process sensory signals differently in different animal species.

Original languageEnglish
Article number13582
JournalInternational Journal of Molecular Sciences
Issue number17
Number of pages29
Publication statusPublished - 1. Sept 2023


  • mammalians
  • spinal cord
  • central canal
  • CSF
  • CSF-cNs
  • intrinsic sensory neurons
  • transient receptor potential channels
  • Cats
  • Neurons
  • Rodentia
  • Rats
  • Animals
  • Central Nervous System
  • Spinal Cord
  • Primates
  • Mice


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