Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease
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...
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| Format: | Article |
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Elsevier
2025-05-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000907 |
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| author | Margaux Lebouc Léa Bonamy Thibault Dhellemmes Jakob Scharnholz Quentin Richard Gilles Courtand Alexandre Brochard Frédéric Martins Marc Landry Jérôme Baufreton Maurice Garret |
| author_facet | Margaux Lebouc Léa Bonamy Thibault Dhellemmes Jakob Scharnholz Quentin Richard Gilles Courtand Alexandre Brochard Frédéric Martins Marc Landry Jérôme Baufreton Maurice Garret |
| author_sort | Margaux Lebouc |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1a5faa913cbf4c68b714db0f4597d5d4 |
| institution | DOAJ |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-1a5faa913cbf4c68b714db0f4597d5d42025-08-20T03:08:47ZengElsevierNeurobiology of Disease1095-953X2025-05-0120810687410.1016/j.nbd.2025.106874Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's diseaseMargaux Lebouc0Léa Bonamy1Thibault Dhellemmes2Jakob Scharnholz3Quentin Richard4Gilles Courtand5Alexandre Brochard6Frédéric Martins7Marc Landry8Jérôme Baufreton9Maurice Garret10Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceUniv. Bordeaux, CNRS, INCIA, UMR 5297, F-33000 Bordeaux, FranceUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000 Bordeaux, FranceUniv. Bordeaux, INSERM, Neurocentre Magendie, U1215, F-33000 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, FranceUniv. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France; Corresponding author.Univ. Bordeaux, CNRS, INCIA, UMR 5297, F-33000 Bordeaux, FranceHuntington'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.http://www.sciencedirect.com/science/article/pii/S0969996125000907Striatal developmentHuntingtinElectrophysiologyNeuronal excitabilityGlutamatergic transmissionNeuronal morphology |
| spellingShingle | Margaux Lebouc Léa Bonamy Thibault Dhellemmes Jakob Scharnholz Quentin Richard Gilles Courtand Alexandre Brochard Frédéric Martins Marc Landry Jérôme Baufreton Maurice Garret Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease Neurobiology of Disease Striatal development Huntingtin Electrophysiology Neuronal excitability Glutamatergic transmission Neuronal morphology |
| title | Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease |
| title_full | Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease |
| title_fullStr | Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease |
| title_full_unstemmed | Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease |
| title_short | Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease |
| title_sort | developmental alterations of indirect pathway medium spiny neurons in mouse models of huntington s disease |
| topic | Striatal development Huntingtin Electrophysiology Neuronal excitability Glutamatergic transmission Neuronal morphology |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000907 |
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