Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome

doi:10.1073/pnas.0502624102

Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome

^†Child Study Center and ^††Department of Neurobiology, Yale University, New Haven, CT 06520; ^§Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129; ^∥Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215; and ^¶Department of Neurology, Harvard Medical School, Boston, MA 02115

Edited by Rodolfo R. Llinas, New York University Medical Center, New York, NY (received for review March 30, 2005)

Abstract

Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterized by motor and vocal tics. Imaging studies found alterations in caudate (Cd) and putamen volumes. To investigate possible alterations in cell populations, postmortem basal ganglia tissue from individuals with TS and normal controls was analyzed by using unbiased stereological techniques. A markedly higher total neuron number was found in the globus pallidus pars interna (GPi) of TS. In contrast, a lower neuron number and density was observed in the globus pallidus pars externa and in the Cd. An increased number and proportion of the GPi neurons were positive for the calcium-binding protein parvalbumin in tissue from TS subjects, whereas lower densities of parvalbumin-positive interneurons were observed in both the Cd and putamen of TS subjects. This change is consistent with a developmental defect in tangential migration of some GABAergic neurons. The imbalance in striatal and GPi inhibitory neuron distribution suggests that the functional dynamics of cortico-striato-thalamic circuitry are fundamentally altered in severe, persistent TS.

Footnotes

↵ ‡‡ To whom correspondence should be addressed. E-mail: flora.vaccarino{at}yale.edu.
↵ ‡ P.S.A.K. and W.Z. contributed equally to this work.
Author contributions: P.S.A.K., C.B.S., M.L.S., J.F.L., and F.M.V. designed research; P.S.A.K., W.Z., Y.K., H.G., C.B.S., M.L.S., J.F.L., and F.M.V. performed research; M.D. contributed new reagents/analytic tools; P.S.A.K., M.L.S., J.F.L., and F.M.V. analyzed data; and P.S.A.K. and F.M.V. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: TS, Tourette syndrome; Cd, caudate; Pt, putamen; GP, globus pallidus; GPi, GP pars interna; GPe, GP pars externa; BG, basal ganglia; MSN, medium spiny neuron; PV, parvalbumin; NC, normal control; SP, substance P; enk, enkephalin.
↵ §§ Zhuang, P., Hallett, M., Zhang, X. H. & Li, Y., Society for Neuroscience 34th annual meeting, Oct. 23-27, 2004, San Diego (abstr.).