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Bilateral Agenesis of the Hippocampal Dentate Gyrus in a Neurologically Normal Adult

Published online by Cambridge University Press:  02 December 2014

Arthur W. Clark  and
Harvey B. Sarnat
Arthur W. Clark*
Affiliation:
Department of Pathology and Laboratory Medicine, University of Calgary Faculty of Medicine, Calgary AB, Canada Department of Clinical Neurosciences, University of Calgary Faculty of Medicine, Calgary AB, Canada
Harvey B. Sarnat
Affiliation:
Department of Pathology and Laboratory Medicine, University of Calgary Faculty of Medicine, Calgary AB, Canada Department of Clinical Neurosciences, University of Calgary Faculty of Medicine, Calgary AB, Canada Department of Pediatrics, University of Calgary Faculty of Medicine, Calgary AB, Canada
*
Department of Histopathology, Foothills Hospital, 1403 - 29th Street N.W., Calgary, Alberta, T2N 2T9, Canada.
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Abstract:

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Background:

Ontogenic development of granule cells in the hippocampal dentate gyrus is influenced by genes including WNT3, EMX2, NEUROD, and LEF1. Dentate granule cells continue to be generated from stem cell precursors postnatally and during adult life, and are implicated in normal and abnormal neurological function. Developmental privation of dentate granule cells is rare and essentially always occurs in the context of other neurodevelopmental abnormalities. We have found no previous reports of severe, selective agenesis of dentate granule cells in humans.

Methods:

A gross and microscopic examination of the brain included appropriate histochemical and immunohistochemical preparations and examination of the hippocampal formation at multiple levels bilaterally.

Results:

This neurologically normal 82-year-old man was found to have bilateral agenesis of the hippocampal dentate gyrus, no identifiable dentate granule cells, and moderate disorganization of the pyramidal cell layer of Ammon's horn. We found no neurodevelopmental abnormalities outside the hippocampus.

Conclusion:

The hippocampal architectural alterations in this patient are similar to those associated with a murine Lef1 mutation, but our human case does not have the other congenital deficits reported in the Lef1-null mouse. Bilateral agenesis of the hippocampal dentate gyrus, and apparent failure of regeneration of dentate granule cells from stem cells in adult life, may occur without overt clinical neurological deficits.

Résumé:

RÉSUMÉ:Contexte:

L’ontogenèse des cellules étoilées du corps godronné de l’hippocampe est influencée par certains gènes dont WNT3, EMX2, NEUROD et LEF1. Des cellules étoilées du corps godronné continuent d’être produites à partir de cellules souches précurseurs après la naissance de même qu’à l’âge adulte. Elles sont impliquées dans le fonctionnement neurologique normal et anormal. L’absence de développement des cellules étoilées du corps godronné est rare et survient toujours dans le contexte d’autres anomalies neurodéveloppementales. À notre connaissance, il n’existe pas de publication portant sur l’observation d’une agénésie sélective sévère des cellules étoilées du corps godronné chez l’humain.

Méthodes:

Un examen macroscopique et microscopique du cerveau avec préparations histochimiques et immunohistochimiques appropriées et examen bilatéral de l’hippocampe à de multiples niveaux.

Résultats:

Il s’agit d’un homme normal au point de vue neurologique chez qui on a constaté une agénésie bilatérale du corps godronné de l’hippocampe, sans cellules étoilées identifiables, ainsi qu’une désorganisation modérée de la couche de cellules pyramidales de la corne d’Ammon. Nous n’avons pas observé d’anomalies neurodéveloppementales ailleurs qu’à l’hippocampe.

Conclusions:

Les altérations architecturales de l’hippocampe chez ce patient sont semblables à celles observées chez un modèle murin de mutation du gène LEF1. Cependant, notre patient n’a pas les autres déficits congénitaux rapportés chez la souris LEF1-nul. L’agénésie bilatérale du corps godronné de l’hippocampe et l’absence de régénération des cellules étoilées du corps godronné à partir de cellules souches à l’âge adulte peuvent survenir sans déficit neurologique évident.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 33 , Issue 3 , August 2006 , pp. 296 - 301
Copyright
Copyright © The Canadian Journal of Neurological 2006

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