Neuroscience
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The neurotrophin brain-derived neurotrophic factor (BDNF) and the steroid hormone estrogen exhibit potent effects on hippocampal neurons during development and in adulthood. BDNF and estrogen have also been implicated in the etiology of diverse types of neurological disorders or psychiatric illnesses, or have been discussed as potentially important in treatment. Although both are typically studied independently, it has been suggested that BDNF mediates several of the effects of estrogen in the hippocampus, and that these interactions play a role in the normal brain as well as disease. ⋯ Then we consider the results of studies that suggest that 17β-estradiol alters hippocampal function by its influence on BDNF expression in the MF pathway. We also address the hypothesis that estrogen influences the hippocampus by mechanisms related not only to the mature form of BDNF, acting at trkB receptors, but also by regulating the precursor, proBDNF, acting at p75NTR. We suggest that the interactions between BDNF and 17β-estradiol in the MFs are potentially important in the normal function of the hippocampus, and have implications for sex differences in functions that depend on the MFs and in diseases where MF plasticity has been suggested to play an important role, Alzheimer's disease, epilepsy and addiction.
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Brain-derived neurotrophic factor (BDNF) has multiple roles in the central nervous system (CNS), including maintaining cell survival and regulation of synaptic function. In CNS neurons, BDNF triggers activation of phospholipase Cγ (PLCγ), mitogen-activated protein/extracellular signal-regulated kinase (MAPK/ERK), and phosphoinositide 3-kinase (PI3K)/Akt pathways, influencing neuronal cells beneficially through these intracellular signaling cascades. There is evidence to suggest that decreased BDNF expression or function is related to the pathophysiology of brain diseases including psychiatric disorders. ⋯ In animal models of depression, changes in glucocorticoid levels, expression of glucocorticoid receptor (GR), and alterations in BDNF signaling are observed. Interestingly, several studies using in vivo and in vitro systems suggest that glucocorticoids interact with BDNF to ultimately affect CNS function. In the present review, we provide an overview of recent evidence concerning the interaction between BDNF and glucocorticoids.
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Glucocorticoids serve as key stress response hormones that facilitate stress coping. However, sustained glucocorticoid exposure is associated with adverse consequences on the brain, in particular within the hippocampus. Chronic glucocorticoid exposure evokes neuronal cell damage and dendritic atrophy, reduces hippocampal neurogenesis and impairs synaptic plasticity. ⋯ Further, we delineate potential lines of future investigation to address hitherto unexplored aspects of the influence of glucocorticoids on BDNF. Finally, we discuss the current understanding of the contribution of BDNF to the modulation of structural and functional plasticity by glucocorticoids, in particular in the context of the hippocampus. Understanding the mechanistic crosstalk between glucocorticoids and BDNF holds promise for the identification of potential therapeutic targets for disorders associated with the dysfunction of stress hormone pathways.
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Neurotrophic factors and steroid hormones interact to regulate a variety of neuronal processes such as neurite outgrowth, differentiation, and neuroprotection. The coexpression of steroid hormone and neurotrophin receptor mRNAs and proteins, as well as their reciprocal regulation provides the necessary substrates for such interactions to occur. This review will focus on androgen brain-derived neurotrophic factor (BDNF) interactions in the spinal cord, describing androgen regulation of BDNF in neuromuscular systems following castration, androgen manipulation, and injury. ⋯ These interactions have important implications for the maintenance of motoneuron morphology. Finally, androgens interact with BDNF after injury, influencing soma size, dendritic morphology, and axon regeneration. Together, these findings provide further insight into the development and maintenance of neuromuscular systems and have implications for the neurotherapeutic/neuroprotective roles of androgens and trophic factors in the treatment of motoneuron disease and recovery from injury.
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Stress has long been associated with the development of neuropsychiatric and neurological disorders. The effects of stress vary depending upon the age during which the stress is incurred, the duration and severity of the stressor, and can further be influenced by levels of circulating gonadal hormones. To date, the majority of research investigating the link between stress and pathology development has focused on stress hormone secretion, receptor activity, and their impact on neuronal development and functioning in developing and adult male and female rodents. ⋯ Specifically, stress-induced alterations in growth factors such as neurotrophins, in particular brain-derived neurotrophic factor (BDNF), have been identified as a strong candidate modulating stress-associated pathology. Furthermore, changing expression of BDNF and its receptors over development and in response to circulating gonadal hormones extend the attractiveness of this candidate signaling pathway for understanding differences in susceptibility to stress. This review focuses on what is known with regard to the effects of stress on neurotrophin expression in rodents, and the varied effects of stress on BDNF levels as a function of developmental status and sex.