60 YEARS OF NEUROENDOCRINOLOGY: Redefining neuroendocrinology: stress, sex and cognitive and emotional regulation

Abstract

The discovery of steroid hormone receptors in brain regions that mediate every aspect of brain function has broadened the definition of “neuroendocrinology” to include the reciprocal communication between the brain and the body via hormonal and neural pathways. The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neuronal replacement, dendritic remodeling, and synapse turnover. Stress causes an imbalance of neural circuitry subserving cognition, decision-making, anxiety and mood that can alter expression of those behaviors and behavioral states. This imbalance, in turn, affects systemic physiology via neuroendocrine, autonomic, immune and metabolic mediators. In the short term, as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive. But, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic anxiety and depression. There are important sex differences in the brain responses to stressors that are in urgent need of further exploration. Moreover, adverse early-life experience, interacting with alleles of certain genes, produce lasting effects on brain and body over the life-course via epigenetic mechanisms. While prevention is most important, the plasticity of the brain gives hope for therapies that take into consideration brain-body interactions.

Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity

“…As expected from previous work (24), 21-d CRS, which leads to dendritic remodeling in the CA3 hippocampus (6), resulted in a significant increase in adrenal-to-body weight ratio compared with nonstressed mice (Fig. S1) that is consistent with elevated glucocorticoid production contributing to dendritic remodeling (13). Interestingly, 21-d CRS significantly decreased the transcription of the putative presynaptic mGlu2 receptor (Fig.…”

“…However, there are underlying changes that can be seen at the level of gene expression and epigenetic regulation that indicate that the brain is continually changing (9, 10). Epigenetic modifications, such as acetylation of histones, have also been involved in the consolidation of contextual memories that allow the brain to respond and adapt to changes in the environment (11).Among the large number of mediators of brain structural and functional plasticity, the glutamatergic system and BDNF play a key role in mediating the effects of stress on both cognition and psychopathology (1,(12)(13)(14)(15). Animal models have shown that chronic stress effects on dendritic remodeling are blocked by blocking NMDA receptors (1,16) and that adrenalectomy attenuates the acute stress-induced elevations of extracellular glutamate levels in the hippocampus (1, 17).…”

Preconception Alcohol Increases Offspring Vulnerability to Stress

“…Enhanced ACTH and corticosterone responses to stress in rats are known to result from increased CRF and/or AVP levels in the hypothalamus and possibly by impaired negative-feedback control by GR, MR and CRFR1 receptors in the limbic areas and by the POMC-derived peptide β-endorphin in the hypothalamus that functions to terminate stress responses (McEwen et al, 2015;Sarkar and Zhang, 2013). In addition, anxiety-related behavior is regulated by Crfr1 in the amygdala (Gilpin et al, 2015) and NPY in the hypothalamus and limbic areas (Sotnikov et al, 2014).…”

Modeling of human brain diseases in experiments on rodents (brief overview)

“…Отметим, что проблема реализации предрасполо-женности к развитию патологии ЦНС требует особого внимания в случаях, когда в исследование включают проблему формирования реакции оси гипоталамус-гипофиз-надпочечниками (т. е. реакции на стрессор, [37]. Это важно для решения актуальных проблем неврологии и психиатрии, а моделирование этих фено-менов на животных, в особенности в связи проблемой воспроизведения симптомов тревожных расстройств [49], весьма актуально.…”