Regenerative Therapies to Restore Interneuron Disturbances in Experimental Models of Encephalopathy of Prematurity

Autor: Josine E G Vaes, Marthe Kaal, Chantal M Kosmeijer, Myrna J V Brandt, Manon J.N.L. Benders, Cora H. Nijboer, Rik van Vliet
Rok vydání: 2020
Předmět:
Vasoactive intestinal peptide
Hippocampal formation
Systemic inflammation
Hippocampus
lcsh:Chemistry
Pregnancy
GABAergic Neurons
lcsh:QH301-705.5
Spectroscopy
Cerebral Cortex
biology
musculoskeletal
neural
and ocular physiology
neurodevelopmental disorders
insulin-like growth factor I
General Medicine
Computer Science Applications
medicine.anatomical_structure
Hypoxia-Ischemia
Brain
Female
medicine.symptom
medicine.medical_specialty
Interneuron
regenerative medicine
Mesenchymal Stem Cell Transplantation
Inhibitory postsynaptic potential
Article
Catalysis
Inorganic Chemistry
Internal medicine
medicine
Animals
Rats
Wistar
Physical and Theoretical Chemistry
Social Behavior
Molecular Biology
Administration
Intranasal
mesenchymal stem cells
interneurons
business.industry
Dentate gyrus
Organic Chemistry
preterm birth
encephalopathy of prematurity
Oligodendrocyte
Mice
Inbred C57BL
Disease Models
Animal
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
nervous system
biology.protein
business
Parvalbumin
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 1
International Journal of Molecular Sciences, Vol 22, Iss 211, p 211 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22010211
Popis: Encephalopathy of Prematurity (EoP) is a major cause of morbidity in (extreme) preterm neonates. Though the majority of EoP research has focused on failure of oligodendrocyte maturation as an underlying pathophysiological mechanism, recent pioneer work has identified developmental disturbances in inhibitory interneurons to contribute to EoP. Here we investigated interneuron abnormalities in two experimental models of EoP and explored the potential of two promising treatment strategies, namely intranasal mesenchymal stem cells (MSCs) or insulin-like growth factor I (IGF1), to restore interneuron development. In rats, fetal inflammation and postnatal hypoxia led to a transient increase in total cortical interneuron numbers, with a layer-specific deficit in parvalbumin (PV)+ interneurons. Additionally, a transient excess of total cortical cell density was observed, including excitatory neuron numbers. In the hippocampal cornu ammonis (CA) 1 region, long-term deficits in total interneuron numbers and PV+ subtype were observed. In mice subjected to postnatal hypoxia/ischemia and systemic inflammation, total numbers of cortical interneurons remained unaffected
however, subtype analysis revealed a global, transient reduction in PV+ cells and a long-lasting layer-specific increase in vasoactive intestinal polypeptide (VIP)+ cells. In the dentate gyrus, a long-lasting deficit of somatostatin (SST)+ cells was observed. Both intranasal MSC and IGF1 therapy restored the majority of interneuron abnormalities in EoP mice. In line with the histological findings, EoP mice displayed impaired social behavior, which was partly restored by the therapies. In conclusion, induction of experimental EoP is associated with model-specific disturbances in interneuron development. In addition, intranasal MSCs and IGF1 are promising therapeutic strategies to aid interneuron development after EoP.
Databáze: OpenAIRE
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