Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-22T11:58:24.523Z Has data issue: false hasContentIssue false
  • English
  • Français

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.
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
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

References

1. Knowles, WD. Normal anatomy and neurophysiology of the hippocampal formation. J Clin Neurophysiol. 1992; 9: 252–63.CrossRefGoogle ScholarPubMed
2. Santarelli, L, Saxe, M, Gross, C, Surget, A, Battaglia, F, Dulawa, S, et al. Requirement of hippocampal neurogenesis for the behavioural effects of antidepressants Science. 2003; 301: 805–9.Google Scholar
3. Vollmayr, B, Simonis, C, Weber, S, Gass, P, Henn, F. Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol Psychiatry. 2003; 54: 1035–40.CrossRefGoogle Scholar
4. Sloviter, RS. The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. Ann Neurol. 1994; 35: 640–54.CrossRefGoogle Scholar
5. Nadler, JV. The recurrent mossy fiber pathway of the epileptic brain. Neurochem Res. 2003; 28: 1649–58.CrossRefGoogle ScholarPubMed
6. Treves, A, Rolls, ET. Computational analysis of the role of the hippocampus in memory. Hippocampus. 1994; 4: 374–91.Google Scholar
7. Prickaerts, J, Koopmans, G, Blokland, A, Scheepens, A. Learning and adult neurogenesis: survival with or without proliferation? Neurobiol Learn Mem. 2004; 81: 1-11.Google Scholar
8. Vaher, PR, Luine, VN, Gould, E, McEwen, BS. Effects of adrenalectomy on spatial memory performance and dentate gyrus morphology. Brain Res. 1994; 656: 71–8.CrossRefGoogle ScholarPubMed
9. McNaughton, BL, Barnes, CA, Meltzer, J, Sutherland, RJ. Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge. Exp Brain Res. 1989; 76: 485–96.CrossRefGoogle Scholar
10. Eriksson, PS, Perfilieva, E, Björk-Eriksson, T, Alborn, A-M, Nordborg, C, Peterson, DA, et al. Neurogenesis in the adult human hippocampus. Nature Medicine. 1998; 4: 1313–7.Google Scholar
11. Gould, E, Tanapat, P. Stress and hippocampal neurogenesis. Biol Psychiatry. 1999; 46: 1472–9.CrossRefGoogle ScholarPubMed
12. Goldschmidt, RB, Steward, O. Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. Proc Natl Acad Sci USA. 1980; 77: 3047–51.Google Scholar
13. Sloviter, RS, Sollas, AL, Dean, E, Neubort, S. Adrenalectomy-induced granule cell degeneration in the rat hippocampal dentate gyrus: characterization of an in vivo model of controlled neuronal death. J Comp Neurol. 1993; 330: 324–36.CrossRefGoogle Scholar
14. Ogita, K, Nishiyama, N, Sugiyama, C, Higuchi, K, Yoneyama, M, Yoneda, Y. Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: evaluation using adult mice treated with trimethyltin chloride as a model. J Neurosci Res. 2005; 82: 609–21.CrossRefGoogle ScholarPubMed
15. Auer, RN, Wieloch, T, Olsson, Y, Siesjo, BK. The distribution of hypoglycaemic brain damage. Acta Neuropathol. 1984; 64: 177–91.Google Scholar
16. Hudson, AJ, Munoz, DG. A familial syndrome of congenital cataract, mental impairment, and dentate gyrus atrophy. Ann Neurol. 1997; 41: 512–20.Google Scholar
17. Chou, SM, Mizujno, Y, Rothner, AD. Congenital granuloprival hypoplasia of cerebellar and hippocampal cortex. J Child Neurol. 1987; 2: 279–86.CrossRefGoogle ScholarPubMed
18. Yamaguchi, K, Honma, K. Autopsy case of thanatophoric dysplasia: observations on the serial sections of brain. Neuropathology. 2001; 21: 222–8.Google Scholar
19. Sarnat, HB. Cerebral dysgenesis. Embryology and clinical expression. NY, London UK: Oxford University Press, 1992. p. 320–1.Google Scholar
20. Humphrey, T. The development of the human hippocampal fissure. J Anat. 1967; 101: 655–76.Google Scholar
21. Rakic, P, Sidman, RL. Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J Comp Neurol. 1970; 139: 473–500.Google Scholar
22. Muller, F, O’Rahilly, R. The human brain at stages 21-23 with particular reference to the cerebral cortical plate and to the development of the cerebellum. Anat Embryol. 1990; 182: 375–400.CrossRefGoogle Scholar
23. O’Rahilly, R, Muller, F. The embryonic human brain. An atlas of developmental stages. NY,Toronto. Wiley-Liss; 1994. p. 110, 201, 252-3, 284-5.Google Scholar
24. Altman, J, Bayer, SA. Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells. J Comp Neurol. 1990; 301: 325–42.Google Scholar
25. Altman, J, Bayer, SA. Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol. 1990; 301: 365–81.Google Scholar
26. Lie, DC, Song, H, Colamarino, SA, Ming, GL, Gage, FH. Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol. 2004; 44: 399–421.Google Scholar
27. Alvarez-Buylla, A, Lim, DA. For the long run: maintaining germinal niches in the adult brain. Neuron. 2004; 41: 683–6.Google Scholar
28. Ming, GL, Song, HL. Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 2005; 28: 223–50.CrossRefGoogle ScholarPubMed
29. Abrous, DN, Koehl, M, Le Moal, M. Adult neurogenesis: from precursors to network and physiology. Physiol Rev. 2005; 85: 523–69.CrossRefGoogle ScholarPubMed
30. Hagg, T. Molecular regulation of adult CNS neurogenesis: an integrated view. Trends Neurosci. 2005; 28: 589–95.CrossRefGoogle ScholarPubMed
31. Nusse, R, Varmus, HE. Wnt genes. Cell. 1992; 69: 1073–87.Google Scholar
32. Lie, D-C, Colamarino, SA, Song, H-G Désiré, L, Mira, H, Consiglio, A, et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature. 2005; 437: 1370–5.Google Scholar
33. Miyata, T, Maeda, T, Lee, JE. NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Genes Dev. 1999; 13: 1647–52.Google Scholar
34. Kastury, K, Druck, T, Huebner, K, Barletta, C, Acampora, D, Simeone, A, et al. Chromosome locations of human EMX and OTX genes. Genomics. 1994; 22: 41–5.CrossRefGoogle ScholarPubMed
35. Bosetti, A, Faiella, A, Boncinelli, E, Consalez, GG. Linkage mapping of Emx2 to mouse chromosome 19. Mamm Genome. 1997; 8: 71–2.Google Scholar
36. Oldekamp, J, Kraemer, N, Alvarez-Bolado, G, Skutella, T. bHLH gene expression in the Emx2-deficient dentate gyrus reveals defective granule cells and absence of migrating precursors. Cereb Cortex. 2004; 14: 1045–58.Google Scholar
37. Pellegrini, M, Mansouri, A, Simeone, A, Boncinelli, E, Gruss, P. Dentate gyrus formation requires Emx2. Development 1996; 122: 3893–8.Google Scholar
38. Van Genderen, C, Okamura, RM, Farinas, I, Quo, R-G, Parslow, TG, Bruhn, L, et al. Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1 deficient mice. Genes Devel. 1994; 8: 2691–703.Google Scholar
39. Milatovich, A, Travis, A, Grosscheldl, R, Francke, U. Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf. Genomics. 1991; 11: 1040–8.CrossRefGoogle ScholarPubMed
40. Galceran, J, Miyashita-Lin, EM, Devaney, E, Rubenstein, JL, Grosschedl, R. Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development. 2000; 127: 469–82.Google Scholar
41. Zheng, W, Nowakowski, RS, Vaccarino, FM. Fibroblast growth factor 2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone. Devel Neurosci. 2004; 26: 181–96.Google Scholar
42. Hitoshi, S, Seaberg, RM, Koscik, C, Alexson, T, Kusunoki, S, Kanazawa, I, et al. Primitive neural stem cells from the mammalian epiblast differentiate to definite neural stem cells under the control of Notch signaling. Genes Devel. 2004; 18: 1806–11.Google Scholar
43. Kitamura, T, Mishina, M, Sugiyama, H. Enhancement of neurogenesis by running wheel exercises is suppressed in mice lacking NMDA receptor epsilon 1 subunit. Neurosci Res. 2003; 47: 55–63.Google Scholar
44. Nacher, J, Rosell, DR, Alonso-Llosa, G, McEwen, BS. NMDA receptor antagonist treatment induces a long-lasting increase in the number of proliferationg cells, PSA-NCAM-immunoreactive granule neurons and radial glia in the adult rat dentate gyrus. Eur J Neurosci. 2001; 13: 512–20.Google Scholar
45. Kulkarni, VA, Jha, S, Vaidya, VA. Depletion of norepinephrine decreases the proliferation, but does not influence the survival and differentiation, of granule cell progenitors in the adult rat hippocampus. Eur J Neurosci. 2002; 16: 2008–12.Google Scholar
46. Mohapel, P, Leanza, G, Kokaia, M, Lindvall, O. Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning. Neurobiol Aging. 2005; 26: 939–46.Google Scholar
47. Harrist, A, Beech, RD, King, SL, Zanardi, A, Cleary, MA, Caldarone, BJ, et al. Alteration of hippocampal cell proliferation in mice lacking the beta 2 subunit of the neuronal nicotinic acetylcholine receptor. Synapse. 2004; 54: 200–6.Google Scholar
48. Squire, LR, Stark, CE, Clark, RE. The medial temporal lobe. Annu Rev Neurosci. 2004; 27: 279–306.Google Scholar
49. Kesner, RP, Lee, I, Gilbert, P. A behavioural assessment of hippocampal function based on a subregional analysis. RevNeurosci. 2004; 15: 333–51.Google Scholar
50. Masukawa, LM, Burdette, LJ, McGonigle, P, Wang, H, O’Conor, W, Sperling, MR, et al. Physiological and anatomical correlates of the human dentate gyrus: consequences or causes of epilepsy. Adv Neurol. 1999; 79: 781–94.Google ScholarPubMed
51. Sarnat, HB. Agenesis and dysgenesis of the corpus callosum. In: Sarnat, HB, Curataolo, P, editors. Elsevier Handbook of Clinical Neurology. Malformations of the Nervous System. Amsterdam: Elsevier, in press 2006.Google Scholar