Elsevier

Journal of Chemical Neuroanatomy

Volume 4, Issue 4, July–August 1991, Pages 299-309
Journal of Chemical Neuroanatomy

Immunohistochemical mapping of neurophysins and calcitonin gene-related peptide in the human brainstem and cervical spinal cord

https://doi.org/10.1016/0891-0618(91)90020-DGet rights and content

Abstract

Our study investigates the distribution of neurophysins (Nph), proteins that are part of the precursors for vasopressin and oxytocin, and calcitonin gene-related peptide (CGRP) in the human brainstem by immunohistochemistry. Both peptides were found in discrete regions of the human hindbrain. Nph could be demonstrated exclusively in fibers and punctate perineural varicosities that were travelling within the mesencephalic central gray, substantia nigra, as well as locus coeruleus, medial longitudinal fascicle, raphe, nucleus of the solitary tract, lateral reticular nucleus and area postrema. A few varicosities were seen in the substantia gelatinosa of the spinal trigeminal tract and its continuation into the dorsal horn of the cervical spinal cord. In contrast to these observations, CGRP-immunoreactive fibers were found to be densest in the spinal tract of the trigeminal nerve and the dorsal horn of the spinal cord. In addition, fibers and varicosities could be demonstrated in numerous distinct brain regions, such as locus coeruleus and subcoeruleus, solitary tract, cuneate nucleus, raphe and periaqueductal gray. CGRP-immunoreactivity was also present in perikarya in the ventral horn of the spinal cord, as well as motor nuclei of cranial nerves, i.e. hypoglossal nucleus, ambiguus nucleus. Our results suggest that Nph-immunoreactivity in the human brainstem may be present predominantly within long fiber projections from hypothalamic neurosecretory nuclei, in analogy to data obtained from rodents, whereas CGRP may play a role in the branchiomotor system as well as in intrinsic or extrinsic projections involved in autonomic regulation and integration of sensory information.

References (61)

  • B.W. Newton et al.

    Calcitonin gene-related peptide and somatostatin in the rat lumbar spinal cord: sexually dimorphic aspects

    Neuroscience

    (1990)
  • R. Oku et al.

    Calcitonin gene-related peptide modulates calcium mobilization in synaptosomes of rat spinal dorsal horn

    Brain Res.

    (1988)
  • M. Rethelyi et al.

    Distribution of neurons expressing calcitonin gene-related peptide mRNAs in the brain stem, spinal cord and dorsal root ganglia of rat and guinea pig

    Neuroscience

    (1989)
  • P. Rousselot et al.

    Oxytocinergic innervation of the rat spinal cord

    An electron microscopic study

    Brain Research

    (1990)
  • P.M. Sexton et al.

    Localization of binding sites for calcitonin gene-related peptide in rat brain by in vitro autoradiography

    Neuroscience

    (1986)
  • G. Skofitsch et al.

    Calcitonin gene-related peptide: Detailed immunocytochemical distribution in the central nervous system

    Peptides

    (1985)
  • M.V. Sofroniew et al.

    Evidence for direct projection from oxytocin and vasopressin neurons in the hypothalamic paraventricular nucleus to the medulla oblongata: immunohistochemical visualization of both the horseradish peroxidase transported and the peptide produced by the same neurons

    Neurosci. Lett.

    (1981)
  • M.V. Sofroniew

    Morphology of vasopressin and oxytocin neurones and their central vascular projections

  • M.V. Sofroniew

    Vasopressin- and neurophysin-immunoreactive neurons in the septal region, medial amygdala and locus coeruleus in colchicine-treated rats

    Neuroscience

    (1985)
  • W.J. Streit et al.

    Calcitonin gene-related peptide increases in rat facial motoneurons after peripheral nerve transection

    Neurosci. Lett.

    (1989)
  • D.F. Swaab et al.

    The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia

    Brain Res.

    (1985)
  • R.E. Watson et al.

    Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology

    Peptides

    (1986)
  • T.F.C. Batten et al.

    Distribution of calcitonin gene-related peptide-like immunoreactivity in the medulla oblongata of the cat, in relation to choline aeetyltransferase-immunoreactive motoneurones and substance P-immunoreactive fibres

    J. Chem. Neuroanat.

    (1989)
  • J.K. Borcich-Tiller et al.

    Human brain calcitonin gene-related peptide (CGRP) is concentrated in the locus coeruleus

    Neuropeptides

    (1988)
  • H. Braak

    Über die Kerngebiete des menschlichen Hirnstammes, I. Oliva inferior, Nucleus conterminalis und Nucleus vermiformis corporis restiformis

    Z. Zellforsch.

    (1970)
  • H. Braak

    Über die Kerngebiete des menschlichen Hirnstammes, IV. Der Nucleus reticularis lateralis und seine Satelliten

    Z. Zellforsch.

    (1971)
  • R.P. Briner et al.

    Evidence for unmyelinated sensory fibers in human dorsal funiculi

    Brain

    (1988)
  • R.E. Brinton et al.

    Regional distribution of putative vasopressin receptors in rat brain and pituitary by quantitative autoradiography

  • R.M. Buijs

    Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat

    Cell Tissue Res.

    (1978)
  • A.R. Caffé et al.

    Vasopressin immunoreactive cells in the rat dorsomedial hypothalamic region, medial amygdaloid nucleus and locus coeruleus

    Cell Tissue Res.

    (1983)
  • Cited by (57)

    • Acupuncture modulates the abnormal brainstem activity in migraine without aura patients

      2017, NeuroImage: Clinical
      Citation Excerpt :

      Recent studies suggested that the neuropeptide calcitonin gene-related peptide (CGRP) may play a critical role in the central and peripheral pathways leading to a migraine attack (Wrobel Goldberg and Silberstein, 2015). CGRP and its receptor components were found in different subregions of TCC in both humans and rats (Unger and Lange, 1991; Van Rossum et al., 1997). A more recent study showed an inhibitory effect of CGRP on mechanically evoked activity in the spinal trigeminal nuclei after pretreatment with glyceryl trinitrate in rats (Covasala et al., 2012).

    • Targeting of calcitonin gene-related peptide action as a new strategy for migraine treatment

      2016, Neurologia i Neurochirurgia Polska
      Citation Excerpt :

      This supports hypothesis that pathophysiology of migraine involves both altered sensory perception of non-noxious stimuli and altered trigeminovascular activation. In both these processes CGRP plays crucial role – peripherally by mediating vasodilatation via smooth muscle cell receptors and centrally by mediating the transmission of pain in the brainstem and second or third-order neurons [37]. CGRP is present in nerve cell bodies of more than 40% of the neurons in the trigeminal ganglion [9].

    • Deficiency of female sex hormones augments PGE<inf>2</inf> and CGRP levels within midbrain periaqueductal gray

      2014, Journal of the Neurological Sciences
      Citation Excerpt :

      Thus, it is well reasoned that amplified expression of EP3 receptors in the dorsolateral PAG induced by a lack of female sex hormones is likely to de-inhibit the descending pain process whereas vasoconstriction regulated by sympathetic nervous system is blunted, all of which are mainly present during migraine attack. CGRP and its receptors have been reported to contribute to development of migraine [13,23,24]. Prior studies have further demonstrated that PGE2 can increase the release of CGRP from the central terminals of trigeminal neurons [25], suggesting that PGE2 plays an important role in modulating the transmission of nociceptive information of relevance to migraine headache via CGRP mechanisms.

    • Periaqueductal Gray

      2012, The Human Nervous System, Third Edition
    • Mapping of CGRP in the alpaca (Lama pacos) brainstem

      2008, Journal of Chemical Neuroanatomy
    • CGRP: Sensory neuropeptide with multiple neurologic implications

      2011, Neurology
      Citation Excerpt :

      These 2 CGRP peptides differ from each other by 3 amino acids and have so far proved to be indistinguishable in their biological activities. CGRP is widely expressed in the central and peripheral nervous systems1,12–15 and frequently coexists and interacts with other neurotransmitters.1 This review focuses on the distribution and functions of CGRP as a sensory neurotransmitter.

    View all citing articles on Scopus
    View full text