Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner
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Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner. / Vasistha, Navneet A; Pardo-Navarro, Maria; Gasthaus, Janina; Weijers, Dilys; Müller, Michaela K; García-González, Diego; Malwade, Susmita; Korshunova, Irina; Pfisterer, Ulrich; von Engelhardt, Jakob; Hougaard, Karin S; Khodosevich, Konstantin.
In: Molecular Psychiatry, Vol. 25, 2020, p. 2313-2329.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner
AU - Vasistha, Navneet A
AU - Pardo-Navarro, Maria
AU - Gasthaus, Janina
AU - Weijers, Dilys
AU - Müller, Michaela K
AU - García-González, Diego
AU - Malwade, Susmita
AU - Korshunova, Irina
AU - Pfisterer, Ulrich
AU - von Engelhardt, Jakob
AU - Hougaard, Karin S
AU - Khodosevich, Konstantin
PY - 2020
Y1 - 2020
N2 - Severe infections during pregnancy are one of the major risk factors for cognitive impairment in the offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brains and how the impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e., proliferation of precursor cells, migration and positioning of neuroblasts, as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, and changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally derived insults have developmental stage-dependent effects, which contribute to the complex etiology of cognitive impairment in the affected offspring.
AB - Severe infections during pregnancy are one of the major risk factors for cognitive impairment in the offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brains and how the impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e., proliferation of precursor cells, migration and positioning of neuroblasts, as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, and changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally derived insults have developmental stage-dependent effects, which contribute to the complex etiology of cognitive impairment in the affected offspring.
U2 - 10.1038/s41380-019-0539-5
DO - 10.1038/s41380-019-0539-5
M3 - Journal article
C2 - 31595033
VL - 25
SP - 2313
EP - 2329
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
ER -
ID: 228734061