Abstract
Early life stress (ELS) causes long-lasting changes in brain plasticity induced by the exposure to stress factors acting prenatally or in the early postnatal ontogenesis due to hyperactivation of hypothalamic-pituitary-adrenal axis and sympathetic nervous system, development of neuroinflammation, aberrant neurogenesis and angiogenesis, and significant alterations in brain metabolism that lead to neurological deficits and higher susceptibility to development of brain disorders later in the life. As a key component of complex pathogenesis, ELS-mediated changes in brain metabolism associate with development of mitochondrial dysfunction, loss of appropriate mitochondria quality control and mitochondrial dynamics, deregulation of metabolic reprogramming. These mechanisms are particularly critical for maintaining the pool and development of brain cells within neurogenic and angiogenic niches. In this review, we focus on brain mitochondria and energy metabolism related to tightly coupled neurogenic and angiogenic events in healthy and ELS-affected brain, and new opportunities to develop efficient therapeutic strategies aimed to restore brain metabolism and reduce ELS-induced impairments of brain plasticity.
Highlights
Life stress (ELS) is a well-known phenomenon underlying long-lasting changes in brain plasticity caused by the exposure to stress factors acting prenatally or in the early postnatal ontogenesis [1]
In human embryonic stem cells, NAD+ increases mitochondrial oxidative metabolism, partially suppresses glycolysis, stimulates amino acid turnover, doubles the consumption of glutamine, and these effects are coupled with the expression of markers of pluripotency and proliferation, thereby suggesting that NAD+ is required for self-renewal and prevention of differentiation of stem cells [166]
There is growing evidence that metabolic status of brain cells controls brain plasticity and vulnerability to the action of stimuli affecting brain development [226], and it was clearly demonstrated in various physiological conditions or brain diseases, including those caused by Early life stress (ELS) (Figure 3)
Summary
Life stress (ELS) is a well-known phenomenon underlying long-lasting changes in brain plasticity caused by the exposure to stress factors acting prenatally or in the early postnatal ontogenesis [1]. While talking on ELS-driven impairment of brain plasticity, the following issues should be taken into consideration: (i) stress should be defined as any environmental stimulus which exceeds the physiological regulatory capacity of an organism and cannot be controlled efficiently [15]; (ii) effects of stress on neurogenesis and angiogenesis might be contradictory—enhancement, suppression, or deregulation—probably because of variable sensitivity at different stages of ontogenesis, or due to gender-specific response: maternal deprivation results in opposite changes in hippocampal neurogenesis in male and female offspring [14,32]; (iii) angiogenesis and neurogenesis are intrinsically coupled mechanisms in the developing and mature brain: vascular scaffold supports neural stem cells (NSCs) and neural progenitor cells (NPCs) maintenance, proliferation, differentiation, and migration of their progeny, whereas NSCs/NPCs stimulate establishment of new cerebral microvessels [33,34]; (iv) consequences of ELS-altered neurogenesis might be quite different in rodents and in mammals with big-sized brains because of unequal contribution of adult-born immature neurons within the neurovascular niches (NVNs) or non-newly generated immature cortical neurons (nng-Ins) to the brain plasticity [35]; (v). We will mainly focus on brain mitochondria and energy metabolism related to neurogenic and angiogenic events in healthy and ELS-affected brain, and new opportunities to develop efficient therapeutic strategies aimed to restore brain metabolism and reduce ELS-induced impairments of brain plasticity
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