Interneuron deficits in patients with the Miller-Dieker syndrome

MacLean Pancoast, William Dobyns, Jeffrey A. Golden

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Lissencephaly is characterized by a thickened cortex and loss of gyri, resulting in the brain having a smooth surface. Patients with lissencephaly frequently exhibit epilepsy and mental retardation, conditions often associated with a defect in inhibitory neurons. While lissencephaly has traditionally been considered a disorder of radial migration, recent data indicate interneurons migrate non-radially, while projection neurons migrate radially. To determine if an interneuron defect, and therefore a non-radial migration defect, exists in patients with lissencephaly, we studied the calretinin-expressing interneuron subpopulation in the brains from two fetuses and two children with lissencephaly and a deletion involving 17p13 deletion (Miller-Dieker syndrome) along with age-matched controls. Our data indicate fetuses with the Miller-Dieker syndrome have a significant (tenfold) reduction in the number of calretinin-expressing interneurons present, whereas minimal reductions in the number of calretinin-expressing interneurons are present in children with this disorder. These data parallel those seen in the Lis1+/- mouse model of human lissencephaly, and are consistent with a non-radial cell migration defect in humans. Thus, when considering the pathogenesis of human lissencephaly and the clinical manifestations in these patients, defects in both non-radial cell migration (inhibitory interneurons) and radial migration (excitatory projection neurons) must be considered.

Original languageEnglish (US)
Pages (from-to)400-404
Number of pages5
JournalActa Neuropathologica
Volume109
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

Keywords

  • Calretinin
  • Interneuron
  • Lissencephaly
  • Miller-Dieker syndrome
  • Radial and non-radial cell migration

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