title: Brainstem and basal ganglia lesions in xeroderma pigmentosum group A.
abstract: Xeroderma pigmentosum group A (XPA) is a hereditary disorder characterized by cutaneous symptoms and progressive neurodegeneration. Since XPA patients exhibit peripheral neuropathy, neuronal deafness, rigidity, dysphagia, and laryngeal dystonia, it is indispensable for investigation of the neurodegeneration to analyze brainstem and basal ganglia lesions clinically and pathologically; we have previously shown the role of oxidative stress in the development of basal ganglia lesions. Here we immunohistochemically examined the expression of neurotransmitters, calcium-binding proteins, and neuropeptides in the brainstem, basal ganglia, and thalamus in 5 XPA autopsy cases. In the brainstem, immunoreactivity for tyrosine hydroxylase, tryptophan hydroxylase, and calbindin-D28K was severely reduced throughout the brainstem in all the XPA cases. Nevertheless, the expressions of parvalbumin, substance P, and methionine-enkephalin in the brainstem were comparatively preserved; the exception being reduced immunoreactivity for them in the cochlear and dorsal column nuclei in 3 cases. The large cell neurons in the putamen were preferentially reduced, the immunoreactivity for tyrosine hydroxylase reflecting the dopaminergic afferent and efferent pathways was severely affected, and the expression of 3 calcium binding proteins (i.e. parvalbumin, calbindin-D28K, and calretinin) was disturbed in various ways. The expression of substance P and methionine-enkephalin, which are involved in the efferent pathways in the basal ganglia, in the globus pallidus and substantia nigra was spared. It is speculated that the selective damage to the dopamine system in the basal ganglia and the disturbed monoaminergic expression in the brainstem could be related to clinical abnormalities such as the rigidity, laryngeal dystonia, and several neurophysiological changes. Functional analysis of autopsy brains will facilitate clarification of the pathogenesis of the neurodegeneration in XPA.
authors.affiliation: Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashi-dai, Fuchu-shi, Tokyo 183-8526, Japan. mahayasi@tmin.ac.jp
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Araki
authors.forename: Jun
authors.initials: J
authors.lastname: Kohyama
authors.forename: Kei
authors.initials: K
authors.lastname: Shioda
authors.forename: Ryo
authors.initials: R
authors.lastname: Fukatsu
authors.forename: Kimiko
authors.initials: K
authors.lastname: Tamagawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology*; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology*; D002102:Cadaver; D064092:Calbindin 1; D064032:Calbindin 2; D064026:Calbindins; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010320:Parvalbumins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000378:metabolism / Q000473:pathology*
chemical_list: C576498:CALB1 protein, human; C576764:CALB2 protein, human; D064092:Calbindin 1; D064032:Calbindin 2; D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D014446:Tyrosine 3-Monooxygenase