Changes of Neurotransmitters in the Brainstem of Patients with Respiratory-Pattern Disorders During Childhood

Yoshiaki Saito; Masayuki Ito; Yuri Ozawa; Toshimasa Obonai; Yasutsugu Kobayashi; Kazuhiko Washizawa; Yoshiteru Ohsone; Takeshi Takami; Kikuko Oku; Sachio Takashima

doi:10.1055/s-2007-973478

Neuropediatrics 1999; 30(3): 133-140
DOI: 10.1055/s-2007-973478

Original articles

Changes of Neurotransmitters in the Brainstem of Patients with Respiratory-Pattern Disorders During Childhood

Yoshiaki Saito¹ , Masayuki Ito¹ , Yuri Ozawa¹ , Toshimasa Obonai¹ , Yasutsugu Kobayashi² , Kazuhiko Washizawa³ , Yoshiteru Ohsone⁴ , Takeshi Takami⁵ , Kikuko Oku⁶ , Sachio Takashima¹

¹Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan,
²Department of Pathology, Osaka City General Hospital,
³Department of Pediatrics, Nagano Red Cross Hospital,
⁴Department of Neonatology, Kimitsu Central Hospital,
⁵Department of Pediatrics, Tokyo Medical University, and
⁶Department of Pediatrics, Kawaguchi Municipal Medical Center

Abstract

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Abstract

We examined neuropathologically and immunohistochemically the respiratory centers in the brainstem of two patients with Joubert syndrome (JS), three patients with congenital central hypoventilation syndrome (CCHS) and a patient with apneustic breathing (prolonged inspiratory pause) due to unknown etiology.

Immunoreactivity (IR) of tryptophan hydroxylase (TPH) was decreased in the dorsal raphe nuclei of two patients with JS compared with age-matched controls, as well as in two patients with Dandy-Walker malformation. The two JS patients showed vermian defect and elongated cerebellar peduncles, and peculiar vascularities in the midline of the whole brainstem were also noted in one of these patients. These findings, as a whole, confirm that the midline structures of brainstem are disordered both structurally and functionally in JS, conceivably resulting in respiratory patterns and psychomotor deficits. IR of serotonin 1A receptor showed no significant changes in the medulla oblongata of these patients, however.

In the parabrachial complex, IR of substance P was increased in two patients with CCHS, and one with apneustic breathing. IR of tyrosine hydroxylase was also increased in the latter. The brainstem of these patients showed reactive astrogliosis. These findings suggest preceding hypoxic episodes as well as an increased activity in the parabrachial complex which plays an important role in conducting the driving force to the medullary respiratory neurons from ascending sensory pathways.

Key words

Serotonin - Substance P - Joubert syndrome - Congenital central hypoventilation syndrome - Apneusis

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