de Pablos, R. M. et al. Stress increases vulnerability to inflammation in the rat prefrontal cortex. J. Neurosci. 26, 5709-5719
Inflammation could be involved in some neurodegenerative disorders that accompany signs of inflammation. However, because sensitivity to inflammation is not equal in all brain structures, a direct relationship is not clear. Our aim was to test whether some physiological circumstances, such as stress, could enhance susceptibility to inflammation in the prefrontal cortex (PFC), which shows a relative resistance to inflammation. PFC is important in many brain functions and is a target for some neurodegenerative diseases. We induced an inflammatory process by a single intracortical injection of 2 microg of lipopolysaccharide (LPS), a potent proinflammogen, in nonstressed and stressed rats. We evaluated the effect of our treatment on inflammatory markers, neuronal populations, BDNF expression, and behavior of several mitogen-activated protein (MAP) kinases and the transcription factor cAMP response element-binding protein. Stress strengthens the changes induced by LPS injection: microglial activation and proliferation with an increase in the levels of the proinflammatory cytokine tumor necrosis factor-alpha; loss of cells such as astroglia, seen as loss of glial fibrillary acidic protein immunoreactivity, and neurons, studied by neuronal-specific nuclear protein immunohistochemistry and GAD67 and NMDA receptor 1A mRNAs expression by in situ hybridization. A significant increase in the BDNF mRNA expression and modifications in the levels of MAP kinase phosphorylation were also found. In addition, we observed a protective effect from RU486 [mifepristone (11beta-[p-(dimethylamino)phenyl]-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)], a potent inhibitor of the glucocorticoid receptor activation. All of these data show a synergistic effect between inflammation and stress, which could explain the relationship described between stress and some neurodegenerative pathologies.
Available from: Matthew G Frank
- "Exposure to a stressor not only produces a transient neuroinflammatory response, but also alters how an organism responds to a subsequent inflammatory challenge for a period of time after the stress exposure has ended. Several studies have found that prior exposure to a potent acute or chronic stressor potentiates the neuroinflammatory and microglial pro-inflammatory response, as well as the sickness response, to a subsequent immune challenge (de Pablos et al., 2014; de Pablos et al., 2006; Espinosa-Oliva et al., 2011; Frank et al., 2007, 2012; Johnson et al., 2002, 2003, 2004; Munhoz et al., 2006; Weber et al., 2013, 2015; Wohleb et al., 2012; Wohleb et al., 2011). Importantly, in these studies, neuroinflammatory and microglial priming was induced using several types of stressors including chronic social defeat, chronic unpredictable mild stress and acute inescapable tail shock. "
[Show abstract] [Hide abstract]
ABSTRACT: Stress and glucocorticoids (GCs) have universally been considered to be anti-inflammatory, however in recent years, stress and GCs have been found to exert permissive effects (immunological priming) on neuroinflammatory processes. This phenomenon of priming is characterized by prior stress or GC exposure potentiating the neuroinflammatory response to a subsequent immune challenge. A considerable body of evidence is discussed here that supports this permissive effect of stress and GCs.In light of this evidence, a mechanism of neuroinflammatory priming is proposed involving a signal cascade in the brain involving danger-associated molecular patterns (HMGB-1) and inflammasomes (NLRP3), which results in an exaggerated or amplified neuroinflammatory response and subsequently, the amplification of the physiological and behavioral sequelae of this response (i.e. sickness). Finally, we explore the notion that stressor-induced sensitization of the neuroimmune microenvironment may predispose individuals to psychiatric disorders, in which exaggerated innate immune/inflammatory responses in the brain are now thought to play a key role.
Available from: Marta Maria Nowacka
- "Previously, we showed for the first time that LPS given peripherally decreased more BDNF expression in the amygdala and hippocampus of female rats subjected to chronic social stress than in non-stressed rats (Nowacka et al., 2014). It has been reported that a single central LPS administration followed by prolonged stress resulted in an enhancement of BDNF level in the prefrontal cortex (De Pablos et al., 2006) and hippocampus (Espinosa-Oliva et al., 2011) in male lab animals. The opposite effect of LPS in the stressed rats in our research compared with the cited studies is most probably due to the above-mentioned essential differences in the applied experimental procedures. "
[Show abstract] [Hide abstract]
ABSTRACT: Imbalance of brain neural circuitry induced by chronic stress leads to dysregulation of the HPA axis and dysfunction of neuroplasticity. The aim of the study was to investigate the influence of acute immunostimulation on the expression and protein level of BDNF and VEGF in the hypothalamus, pituitary and plasma of female rats subjected to chronic social instability stress. Rats were subjected to 4-week stress procedure, including phases of isolation and crowding, alternated in an unpredictable manner. On the last experimental day, the rats in the estrus phase were injected ip. with LPS (1 mg/kg). All experiments were performed on females being in the same phase of the estrus cycle to avoid alterations in neurotrophin expression. An increase in relative adrenal and thymus weights in the stressed rats were observed. Chronic stress affected more strongly VEGF but not BDNF in the hypothalamus and pituitary gland. In the stressed rats, LPS decreased BDNF and VEGF mRNA levels in both structures and plasma BDNF concentrations. Optical density of VEGF immunoreactivity in the supraoptic nucleus was increased after LPS administration in the stressed rats as compared to the saline-treated stressed group. It may be assumed that chronic social stress makes the SOR neurons sensitive to a peripheral proinflammatory stimulus. Our results indicate that chronic stress enhances vulnerability of BDNF and VEGF response to neuroinflammation in the examined structures, which may be one of the reasons for its role in triggering affective diseases.
Available from: Jose L Venero
- "We and others have demonstrated that chronic stress potentiate the microglial pro - inflammatory response ( de Pablos et al . , 2006 , 2014 ; Tynan et al . , 2010 ; Espinosa - Oliva et al . , 2011 ; Wohleb et al . , 2011 ; Hinwood et al . , 2012 ) . Psychological chronic stress - induced inflammatory changes in microglia / macrophages were blocked by propranolol , an indication of an active role of β - adrenergic receptors in stress - induced microglial pro - inflamma"
[Show abstract] [Hide abstract]
ABSTRACT: This review is aimed to highlight the importance of stress and glucocorticoids (GCs) in modulating the inflammatory response of brain microglia and hence its potential involvement in Parkinson's disease (PD). The role of inflammation in PD has been reviewed extensively in the literature and it is supposed to play a key role in the course of the disease. Historically, GCs have been strongly associated as anti-inflammatory hormones. However, accumulating evidence from the peripheral and central nervous system have clearly revealed that, under specific conditions, GCs may promote brain inflammation including pro-inflammatory activation of microglia. We have summarized relevant data linking PD, neuroinflamamation and chronic stress. The timing and duration of stress response may be critical for delineating an immune response in the brain thus probably explain the dual role of GCs and/or chronic stress in different animal models of PD.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.