Perinatal Ischemia Alters Global Expression of Synaptosomal Proteins Critical for Neural Plasticity in the Developing Mouse Brain

Amanda K. Barks, Montana M. Beeson, Tatyana Matveeva, Jonathan J. Gale, Raghu Rao, Phu V Tran

Research output: Contribution to journalArticle

Abstract

Ischemic perinatal stroke (IPS) affects 1 in 2,300-5,000 live births. Despite a survival rate >95%, approximately 60% of IPS infants develop motor and cognitive impairments. Given the importance of axonal growth and synaptic plasticity in neurocognitive development, our objective was to identify the molecular pathways underlying IPS-Associated synaptic dysfunction using a mouse model. IPS was induced by unilateral ligation of the common carotid artery of postnatal day 10 (P10) mice. Five days after ischemia, sensorimotor and motor functions were assessed by vibrissae-evoked forepaw placement and the tail suspension test respectively, showing evidence of greater impairments in male pups than in female pups. Twenty-four hours after ischemia, both hemispheres were collected and synaptosomal proteins then prepared for quantification, using isobaric tags for relative and absolute quantitation. Seventy-Two of 1,498 qualified proteins were altered in the ischemic hemisphere. Ingenuity Pathway Analysis was used to map these proteins onto molecular networks indicative of reduced neuronal proliferation, survival, and synaptic plasticity, accompanied by reduced PKCα signaling in male, but not female, pups. These effects also occurred in the non-ischemic hemisphere when compared with sham controls. The altered signaling effects may contribute to the sex-specific neurodevelopmental dysfunction following IPS, highlighting potential pathways for targeting during treatment.

Original languageEnglish (US)
Pages (from-to)638-650
Number of pages13
JournalDevelopmental Neuroscience
Volume40
Issue number5-6
DOIs
StatePublished - Jul 1 2019

Fingerprint

Neuronal Plasticity
Ischemia
Stroke
Brain
Proteins
Hindlimb Suspension
Vibrissae
Common Carotid Artery
Live Birth
Ligation
Survival Rate
Growth

Keywords

  • Brain injury
  • Neonatal ischemia
  • Neuronal plasticity
  • Proteome
  • Synaptosome

PubMed: MeSH publication types

  • Journal Article

Cite this

Perinatal Ischemia Alters Global Expression of Synaptosomal Proteins Critical for Neural Plasticity in the Developing Mouse Brain. / Barks, Amanda K.; Beeson, Montana M.; Matveeva, Tatyana; Gale, Jonathan J.; Rao, Raghu; Tran, Phu V.

In: Developmental Neuroscience, Vol. 40, No. 5-6, 01.07.2019, p. 638-650.

Research output: Contribution to journalArticle

Barks, Amanda K. ; Beeson, Montana M. ; Matveeva, Tatyana ; Gale, Jonathan J. ; Rao, Raghu ; Tran, Phu V. / Perinatal Ischemia Alters Global Expression of Synaptosomal Proteins Critical for Neural Plasticity in the Developing Mouse Brain. In: Developmental Neuroscience. 2019 ; Vol. 40, No. 5-6. pp. 638-650.
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