Abstract
Neonatal neuropsychiatric stress induces alterations in neurodevelopment that can lead to irreversible damage to neuronal physiology, and social, behavioral, and cognitive skills. In addition, this culminates to an elevated vulnerability to stress and anxiety later in life. Developmental deficits in hippocampal synaptic function and plasticity are among the primary contributors of detrimental alterations in brain function induced by early-life stress. However, the underlying molecular mechanisms are not completely understood. Localized protein translation, occurring at the synapse and triggered by neuronal activity, is critical for synapse function, maintenance, and plasticity. We used a rodent model of chronic maternal deprivation to characterize the effects of early-life neuropsychiatric stress on localized de novo protein translation at synaptic connections between neurons. Synaptoneurosomal preparations isolated biochemically from the hippocampi of rat pups that were subjected to maternal deprivation were deficient in depolarization-induced activity-dependent protein translation when compared with littermate controls. Conversely, basal unstimulated protein translation was not affected. Moreover, deficits in activity-driven synaptic protein translation were significantly correlated with a reduction in phosphorylated cell survival protein kinase protein B or Akt (p473 Ser and p308 Thr), but not phosphorylated extracellular signal-regulated kinase.
Highlights
Adverse early-life experience, such as neuropsychiatric stress, induces permanent changes in the neurodevelopmental trajectory
Detrimental changes in synapse function and plasticity after exposure to early-life neuropsychiatric stress have been observed by several groups [8,9,10]
Depolarization-induced de novo localized protein translation is deficient in the synaptoneurosomes of maternally separated rat pups
Summary
Adverse early-life experience, such as neuropsychiatric stress, induces permanent changes in the neurodevelopmental trajectory This can lead to permanent alterations in neuronal physiology, deficits in cognitive and social skills, increased behavioral abnormalities, and vulnerability to stress and anxiety later in life [1,2]. Mother–infant interactions are a critical factor for brain development and maturation Alterations in these interactions can result in increased susceptibility to cognitive and behavioral disorders in humans even into adulthood [2,3,4]. Detrimental changes in synapse function and plasticity after exposure to early-life neuropsychiatric stress have been observed by several groups [8,9,10] They are major contributors to the permanent phenotypic effects on behavior, psychology, and cognition [11,12,13,14]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.