Early life stress and brain plasticity: from molecular alterations to aberrant memory and behavior

Abstract

Early life stress (ELS) is one of the most critical factors that could modify brain plasticity, memory and learning abilities, behavioral reactions, and emotional response in adulthood leading to development of different mental disorders. Prenatal and early postnatal periods appear to be the most sensitive periods of brain development in mammals, thereby action of various factors at these stages of brain development might result in neurodegeneration, memory impairment, and mood disorders at later periods of life. Deciphering the processes underlying aberrant neurogenesis, synaptogenesis, and cerebral angiogenesis as well as deeper understanding the effects of ELS on brain development will provide novel approaches to prevent or to cure psychiatric and neurological deficits caused by stressful conditions at the earliest stages of ontogenesis. Neuropeptide oxytocin serves as an amnesic, anti-stress, pro-angiogenic, and neurogenesis-controlling molecule contributing to dramatic changes in brain plasticity in ELS. In the current review, we summarize recent data on molecular mechanisms of ELS-driven changes in brain plasticity with the particular focus on oxytocin-mediated effects on neurogenesis and angiogenesis, memory establishment, and forgetting.

Early Life Stress and Metabolic Plasticity of Brain Cells: Impact on Neurogenesis and Angiogenesis

“…Astroglia-derived lactate affects other NVU/BBB cells, i.e., BMECs may respond to lactate either by activating lactate influx through MCT1 or by initiating signal transduction from lactate GPR81 receptors expressed on their plasma membrane. Experimental data suggest that both these mechanisms are required for maintaining the integrity of BBB as well as for effective angiogenesis/barriergenesis, and they are altered in neuroinflammation and ELS [ 2 , 69 , 92 , 93 , 94 ].…”

“…Various prenatal or early postnatal stimuli can result in the initiation of mechanisms specific for ELS, i.e., hypoxia, toxic agents, aberrant social interactions. It is well-established [ 2 , 3 ] that multiple physiological mechanisms are affected in ELS, thereby leading to impairment of brain development, neurological deficits, and higher susceptibility to development of aging-associated neurodegeneration in latter periods of life. This is known as an early programming phenomenon, or priming of developing brain to pathological conditions due to experiencing the prenatal, intranatal, or early postnatal stress [ 4 ].…”

“…Neurogenesis, synaptic turnover and remodeling of neural circuits are the basis of brain plasticity in developing, mature, and ageing brain [ 2 , 13 ]. ELS affects brain developmental program, embryonic and adult neurogenesis, as well as cerebral angiogenesis that are tightly coordinated in normal conditions.…”

“…These processes demonstrate significant alterations caused by ELS either due to inappropriate development of neurovascular niches (NVNs)—subventricular zone (SVZ) and hippocampal subgranular zone (SGZ), or remarkable changes in the local niche microenvironment induced by high levels of stress hormones and cytokines at the critical and sensitive periods of brain development [ 14 , 15 ]. The common finding is that ELS induces suppression of adult neurogenesis and augments the susceptibility to development of cognitive deficits or depression later in life [ 2 ]. However, there are important issues that should be considered in this context.…”

Central role of the habenulo-interpeduncular system in the neurodevelopmental basis of susceptibility and resilience to anxiety

“…Since many psychiatric diseases are now considered to have a neurodevelopmental origin, caused by an interplay between genes and environment during specific sensitive periods of development (Assary, Vincent et al 2018, Lopatina, Panina et al 2021, susceptibility or resilience should have their roots at these periods. While this hypothesis is widely accepted, the neural circuits and the modifications involved remain to be discovered.…”