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Cholinergic Neurons in Nucleus Subputaminalis in Primary Progressive Aphasia

  • Hayam Hamodat (a1), John D. Fisk (a2) (a3) (a4) (a5) and Sultan Darvesh (a1) (a2) (a5) (a6) (a7)

Abstract:

Background: Primary Progressive Aphasia (PPA) is a syndrome characterized by an isolated impairment of language function at disease onset. The cholinergic system is implicated in language function and cholinergic deficits are seen in the brains of individuals with PPA. One major source of cholinergic innervation of the cerebral cortex is the nucleus basalis of Meynert (NBM) within which lies the nucleus subputaminalis (NSP). This nucleus is postulated to be involved in language function. We compared the abundance of cholinergic neurons in the NBM and NSP of controls and individuals with PPA. Also explored was whether the individuals presenting with PPA, who subsequently developed different clinical and neuropathological profiles, showed similar cholinergic deficits in the NSP. Methods: Cytoarchitecture of the basal forebrain was studied using Nissl staining in control (n = 5) and PPA (n = 5) brains. Choline acetyltransferase (ChAT) immunohistochemical staining labeled cholinergic neurons were quantified using Neurolucida software. Results: In comparison to matched controls, PPA showed reduction of cholinergic neurons in the NBM (t(8) = 4.04, p = 0.0037; Cohen’s effect size value d = 2.62) and the NSP (t(6) = 4.62, p = 0.0042; Cohen’s d effect size d = 2.92). The average percent of cholinergic neuronal loss was relatively higher in the NSP (64.7%) compared to the NBM (47.7%). Conclusion: Regardless of underlying pathology, all cases presenting with PPA showed a marked loss of cholinergic neurons in the NSP, providing further evidence for the importance of this nucleus in language function.

Pertes de neurones cholinergiques dans le nucleus subputaminalis d’individus atteints d’aphasie primaire progressive. Contexte : L’aphasie primaire progressive (APP) constitue un syndrome qui se caractérise par un trouble isolé de la fonction langagière au moment où la maladie manifeste ses premiers signes. On le sait, le système cholinergique est lié à la fonction langagière. Voilà pourquoi des déficits cholinergiques sont observés dans les cerveaux d’individus atteints d’APP. Une source majeure d’innervation cholinergique du cortex cérébral se situe dans le noyau basal de Meynert (NBM), noyau dans lequel on trouve le nucleus subputaminalis (NSP). On tend à penser que ce dernier est impliqué dans la fonction langagière. Nous avons ainsi comparé l’abondance de neurones cholinergiques dans le NBM et le NSP chez des patients atteints d’APP et des témoins. Nous avons aussi tenté de savoir dans quelle mesure les individus atteints d’APP ayant subséquemment développé divers profils cliniques et neuro-pathologiques donnaient à voir les mêmes déficits cholinergiques au niveau du NSP. Méthodes : La cytoarchitectonie du prosencéphale basal a été étudiée au moyen de la méthode de coloration de Nissl. Pour ce faire, 5 cerveaux de témoins et 5 cerveaux d’individus atteint d’APP ont été sélectionnés. De la coloration immunohistochimique à base de choline acétyltransférase (ChAT) a permis d’identifier les neurones cholinergiques. Pour les quantifier, nous avons utilisé le logiciel Neurolucida. Résultats : En comparaison avec les témoins, les individus atteints d’APP ont montré une réduction de leurs neurones cholinergiques dans le NBM (t (8) = 4,04 ; p = 0,0037 ; taille d’effet proposée par Cohen et notée d = 2,62) et le NSP (t (6) = 4,62 ; p = 0,0042 ; taille d’effet proposée par Cohen et notée d = 2,92). Le pourcentage moyen de perte de neurones cholinergiques s’est révélé relativement plus élevé dans le cas du NSP (64,7 %) en comparaison avec le NBM (47,7 %). Conclusion : Sans égard à la présence d’une pathologie sous-jacente, tous les individus atteints d’APP ont montré une perte marquée de neurones cholinergiques dans leur NSP, ce qui apporte une preuve supplémentaire quant à l’importance de ce noyau eu égard à la fonction langagière.

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Corresponding author

Correspondence to: S. Darvesh, Room 1308, Camp Hill Veterans’ Memorial, 5955 Veterans’ Memorial Lane, Halifax, Nova Scotia B3H 2E1, Canada. Email: sultan.darvesh@dal.ca

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Keywords

Cholinergic Neurons in Nucleus Subputaminalis in Primary Progressive Aphasia

  • Hayam Hamodat (a1), John D. Fisk (a2) (a3) (a4) (a5) and Sultan Darvesh (a1) (a2) (a5) (a6) (a7)

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