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Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease

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Název: Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease
Autoři: Margaux Lebouc, Léa Bonamy, Thibault Dhellemmes, Jakob Scharnholz, Quentin Richard, Gilles Courtand, Alexandre Brochard, Frédéric Martins, Marc Landry, Jérôme Baufreton, Maurice Garret
Zdroj: Neurobiology of Disease, Vol 208, Iss , Pp 106874- (2025)
Informace o vydavateli: Elsevier, 2025.
Rok vydání: 2025
Sbírka: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
Témata: Striatal development, Huntingtin, Electrophysiology, Neuronal excitability, Glutamatergic transmission, Neuronal morphology, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Popis: Huntington's disease (HD) is a complex neurodegenerative disorder with cognitive and motor symptoms that typically manifest in adulthood. However, embryonic brain development impairments leading to cortical defects in HD mutation carriers has been shown recently supporting a neurodevelopmental component in HD. Despite HD is primarily recognized as a striatal pathology, developmental alterations in this structure, particularly during the early postnatal period, remain poorly understood. To fill this gap, we examined striatal development in newborn R6/1 mice. We found that D2 receptor-expressing indirect-pathway medium spiny neurons (D2-MSNs) present in the matrix striatal compartment undergo early morphological and electrophysiological maturation. Altered electrophysiological properties were also observed in newborn CAG140 mice. Additionally, we also observed a D2-MSN-selective reduction in glutamatergic cortico-striatal transmission at the beginning of the second postnatal week as well as a reduced projection of D2-MSNs onto the GPe at birth in R6/1 mice. All these alterations were transient with the circuit normalizing after the second postnatal week. These results identify a compartment- and cell-type specific defect in D2-MSNs maturation, which can contribute in their latter vulnerability, as this cell-type is the first to degenerate in HD during adulthood.
Druh dokumentu: article
Popis souboru: electronic resource
Jazyk: English
ISSN: 1095-953X
Relation: http://www.sciencedirect.com/science/article/pii/S0969996125000907; https://doaj.org/toc/1095-953X
DOI: 10.1016/j.nbd.2025.106874
Přístupová URL adresa: https://doaj.org/article/1a5faa913cbf4c68b714db0f4597d5d4
Přístupové číslo: edsdoj.1a5faa913cbf4c68b714db0f4597d5d4
Databáze: Directory of Open Access Journals
Popis
Abstrakt:Huntington's disease (HD) is a complex neurodegenerative disorder with cognitive and motor symptoms that typically manifest in adulthood. However, embryonic brain development impairments leading to cortical defects in HD mutation carriers has been shown recently supporting a neurodevelopmental component in HD. Despite HD is primarily recognized as a striatal pathology, developmental alterations in this structure, particularly during the early postnatal period, remain poorly understood. To fill this gap, we examined striatal development in newborn R6/1 mice. We found that D2 receptor-expressing indirect-pathway medium spiny neurons (D2-MSNs) present in the matrix striatal compartment undergo early morphological and electrophysiological maturation. Altered electrophysiological properties were also observed in newborn CAG140 mice. Additionally, we also observed a D2-MSN-selective reduction in glutamatergic cortico-striatal transmission at the beginning of the second postnatal week as well as a reduced projection of D2-MSNs onto the GPe at birth in R6/1 mice. All these alterations were transient with the circuit normalizing after the second postnatal week. These results identify a compartment- and cell-type specific defect in D2-MSNs maturation, which can contribute in their latter vulnerability, as this cell-type is the first to degenerate in HD during adulthood.
ISSN:1095953X
DOI:10.1016/j.nbd.2025.106874