Advertisement

Reduced expression of neuropeptides can be related to respiratory disturbances in Rett syndrome

      Abstract

      We immunohistochemically examined neurotransmitter systems, which function in the brainstem and are involved in neuronal organization of respiration, in an autopsy brain from a patient with Rett syndrome (RS). Immunoreactivity (IR) for tyrosine hydroxylase, a functional marker for catecholaminergic neurons, was severely reduced in the locus ceruleus, while that for tryptophan hydroxylase involved in serotonin synthesis was spared in the raphe nuclei. In the brainstem, IR for substance P (SP) was reduced in the parabrachial complex and that for methionine-enkephalin (met-enk) was affected in the parabrachial, hypoglossal, dorsal vagal and solitary nuclei. In addition, expressions of these neuropeptides were also disturbed in the basal ganglia. A widespread altered expression of antagonistic neuropeptides, SP and met-enk, may be involved in the pathogenesis of RS, especially in its respiratory manifestation.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lugaresi E.
        • Cirignotta F.
        • Pasquale M.
        Abnormal breathing in the Rett syndrome.
        Brain Dev. 1985; 7: 329-333
        • Glaze D.G.
        • Frost J.D.
        • Zoghbi H.Y.
        • Percy A.K.
        Rett's syndrome: characterization of respiratory patterns and sleep.
        Ann Neurol. 1987; 21: 377-382
        • Segawa M.
        • Nomura Y.
        Polysomnography in the Rett syndrome.
        Brain Dev. 1992; 14: S46-S54
        • Johnston M.V.
        • Hofmann C.
        • Blue M.E.
        Neurobiology of Rett syndrome.
        Neuropediatrics. 1995; 26: 119-122
        • Matsuishi T.
        • Nagamitsu S.
        • Yamashita Y.
        • Murakami Y.
        • Kimura A.
        • Sakai T.
        • et al.
        Decreased cerebrospinal fluid levels of substance P in patients with Rett syndrome.
        Ann Neurol. 1997; 42: 978-981
        • Deguchi K.
        • Antalffy B.A.
        • Teohill L.J.
        • Chakraborty S.
        • Glaze D.G.
        • Armstrong D.D.
        Substance P immunoreactivity in Rett syndrome.
        Pediatr Neurol. 2000; 22: 259-266
        • Jellinger K.
        • Armstrong D.
        • Zoghbi H.Y.
        • Percy A.K.
        Neuropathology of Rett syndrome.
        Acta Neuropathol. 1988; 76: 142-158
        • Saito Y.
        • Ito M.
        • Ozawa Y.
        • Obonai T.
        • Kobayashi Y.
        • Washizawa K.
        • et al.
        Changes of neurotransmitters in the brainstem of patients with respiratory pattern disorders during childhood.
        Neuropediatrics. 1999; 30: 133-140
        • Hagberg B.
        Clinical criteria, stages and natural history.
        in: Hagberg B. Rett syndrome-clinical and biological aspects. Mac Keith Press, London1993: 4-20
        • Amir R.E.
        • Van den Veyver I.B.
        • Wan M.
        • Tran C.Q.
        • Francke U.
        • Zoghbi H.Y.
        Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
        Nat Genet. 1999; 23: 185-188
        • Brase D.A.
        • Myer E.C.
        • Dewey W.L.
        Possible hyperendorphinergic pathophysiology of the Rett syndrome.
        Life Sci. 1989; 45: 359-366
        • Myer E.C.
        • Tripathi H.L.
        • Brase D.A.
        • Dewey W.L.
        Elevated CSF beta-endorphin immunoreactivity in Rett's syndrome.
        Neurology. 1992; 42: 357-360
        • Percy A.K.
        • Glaze D.G.
        • Schlutz R.J.
        • Zoghbi H.Y.
        • Williamson D.
        • Frost S.D.
        • et al.
        Rett syndrome: controlled study of an oral opiate antagonist, naltrexone.
        Ann Neurol. 1994; 35: 464-470
        • Kuhar M.J.
        Opiate receptors: some anatomical and physiological aspects.
        Ann N Y Acad Sci. 1978; 311: 35-48
        • Hedner Z.C.
        • Hedner T.
        Substance P-induced respiratory excitation is blunted by δ-receptor specific opioids in the rat medulla oblongata.
        Acta Physiol Scand. 1996; 157: 165-173
        • Yan S.
        • Zhang C.
        • Laferriere A.
        • Moss I.R.
        Met-enkephalin-like immunoreactivity in microdyalisates from nucleus tractus solitarii in piglets during normoxia and hypoxia.
        Brain Res. 1995; 687: 217-220
        • Matsuishi T.
        • Urabe F.
        • Komori H.
        • Yamashita Y.
        • Naito E.
        • Kuroda Y.
        • et al.
        The Rett syndrome and CSF lactate acid patterns.
        Brain Dev. 1992; 14: 68-70
        • Lappalainen R.
        • Riikonen R.S.
        Elevated CSF lactate in the Rett syndrome: cause or consequence?.
        Brain Dev. 1994; 16: 399-401
      1. Anzai Y, Ohya T. An effective gastrostomy for respiratory disturbance of Rett's syndrome. World Congress on Rett Syndrome 2000, July 24–27. Karuizawa: Nagano, Japan, 2000.

        • Joubert M.
        • Eisenring J.J.
        • Robb J.P.
        • Andermann F.
        Familial agenesis of the cerebellar vermis.
        Neurology. 1969; 19: 813-825
        • Goto S.
        • Hirano A.
        • Matsumoto S.
        Met-enkephalin immunoreactivity in the basal ganglia in Parkinson's disease and striatonigral degeneration.
        Neurology. 1990; 40: 1051-1056
        • Saito Y.
        • Ito M.
        • Hanaoka S.
        • Ohama E.
        • Akaboshi S.
        • Takashima S.
        Dopamine receptor upregulation in Lesch–Nyhan syndrome: a post-mortem study.
        Neuropediatrics. 1999; 30: 66-71
        • Wenk G.L.
        • Naidu S.
        • Casanova M.F.
        • Kitt C.A.
        • Moser H.
        Altered neurochemical markers in Rett's syndrome.
        Neurology. 1991; 41: 1753-1756