Alterations of GABAergic neurons in the basal ganglia of patients with progressive supranuclear palsy: an in situ hybridization study of GAD67 messenger RNA.
We analyzed postmortem GABAergic neurons in the basal ganglia of three patients with progressive supranuclear palsy (PSP) and four matched controls by means of glutamic acid decarboxylase (M(r) 67,000 [GAD67]) mRNA in situ hybridization. In PSP, we found a 50 to 60% decrease in the number of neurons expressing GAD67 mRNA in the caudate nucleus, ventral striatum, and the external and internal pallidum. The expression of GAD67 mRNA per neuron was reduced in the caudate nucleus and putamen (-43%), the ventral striatum (-55%), and the external and internal pallidum (-59% and -68%). Our data indicate that striatal and pallidal GABAergic neurotransmission is markedly reduced in PSP and we suggest that this alteration may account for the motor and cognitive symptoms observed in PSP. Furthermore, the destruction of the basal ganglia output systems may explain the lack of responsiveness to L-dopa therapy of PSP patients.
Levy
R
R
Laboratoire de Médecine Expérimentale, INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Ruberg
M
M
Herrero
M T
MT
Villares
J
J
Javoy-Agid
F
F
Agid
Y
Y
Hirsch
E C
EC
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001344:Autopsy; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002421:Caudate Nucleus / Q000201:enzymology; D015870:Gene Expression; D005917:Globus Pallidus / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D006801:Humans; D017403:In Situ Hybridization; D009474:Neurons / Q000201:enzymology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D012016:Reference Values; D012680:Sensitivity and Specificity; D013494:Supranuclear Palsy, Progressive / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase