Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior

Lowry, Christopher A.; Hollis, Jacob Harvey; Vries, Annick de; Pan, Bin; Brunet, Laura Rosa; Hunt, Jon; Paton, Julian F. R.; Kampen, E. van; Knight, David; Evans, Andrew K.; Rook, G.A.W.; Lightman, Stafford L.

doi:10.1016/j.neuroscience.2007.01.067

Cited by 157 publications

(116 citation statements)

References 72 publications

(124 reference statements)

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“…The nonpathogenic Mycobacterium vaccae leads to activation of the peripheral immune system. The Th1 and Treg, but not Th2, mediated immune activation stimulates a subset of 5-HT neurons in the dorsal raphe nucleus of mice and increases serotonin turnover in the ventromedial prefrontal cortex (Lowry et al, 2007). This finding illustrates the fact that the type of peripheral immune response determines the effects on central 5-HT neurons.…”

Section: Microbiota and Humoral Responsesmentioning

confidence: 80%

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Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

191

121

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There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.

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Section: Microbiota and Humoral Responsesmentioning

confidence: 80%

“…One investigated mechanism through which immune activation may alter behavior is via actions on serotonergic systems (Lowry et al, 2007). The nonpathogenic Mycobacterium vaccae leads to activation of the peripheral immune system.…”

Section: Microbiota and Humoral Responsesmentioning

confidence: 99%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

191

121

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“…The most recent and surprising finding in this collection of studies is that certain sorts of depression might also be explained by the hygiene hypothesis (Lowry et al, 2007;Rook & Lowry, 2008;Spiga, Lightman, Shekar, & Lowry, 2006). As I have noted, the documentation for this link is less robust than that between the hygiene hypothesis and the other pathologies mentioned.…”

Section: Bacteria and Depressionmentioning

confidence: 87%

Gender and the hygiene hypothesis

Clough

2011

Social Science & Medicine

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a b s t r a c tThe hygiene hypothesis offers an explanation for the correlation, well-established in the industrialized nations of North and West, between increased hygiene and sanitation, and increased rates of asthma and allergies. Recent studies have added to the scope of the hypothesis, showing a link between decreased exposure to certain bacteria and parasitic worms, and increased rates of depression and intestinal autoimmune disorders, respectively. What remains less often discussed in the research on these links is that women have higher rates than men of asthma and allergies, as well as many auto-immune disorders, and also depression. The current paper introduces a feminist understanding of gender socialization to the epidemiological and immunological picture. That standards of cleanliness are generally higher for girls than boys, especially under the age of five when children are more likely to be under close adult supervision, is a robust phenomenon in industrialized nations, and some research points to a crosscultural pattern. I conclude that, insofar as the hygiene hypothesis successfully identifies standards of hygiene and sanitation as mediators of immune health, then attention to the relevant patterns of gender socialization is important. The review also makes clear that adding a feminist analysis of gender socialization to the hygiene hypothesis helps explain variation in morbidity rates not addressed by other sources and responds to a number of outstanding puzzles in current research. Alternative explanations for the sex differences in the relevant morbidity rates are also discussed (e.g., the effects of estrogens). Finally, new sources of evidence for the hygiene hypothesis are suggested in the form of cross-cultural and other natural experiments.

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“…This would be consistent with the proposed implication of these brain areas in affective disorders 76 , but it does not necessarily mean that there is a full overlap between the brain areas that are involved in major depressive disorders and those that are activated in cytokine-induced depression. Indeed, in a model of localized bronchopulmonary immune activation, only a specific subset of serotonergic neurons in the interfascicular region of the dorsal raphe nucleus were activated, as assessed by increased c-fos expression 77 . This subpopulation of serotonergic neurons is not the same as that which responds to anxiety-inducing stimuli.…”

Section: Neuroanatomy Of Cytokine-induced Depressionmentioning

confidence: 99%

From inflammation to sickness and depression: when the immune system subjugates the brain

et al. 2008

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In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.Anyone who has experienced a viral or bacterial infection knows what it means to feel sick. The behaviour of sick people changes dramatically; they often feel feverish and nauseated, ignore food and beverages, and lose interest in their physical and social environments. They tire easily and their sleep is often fragmented. In addition, they feel depressed and irritable, and can experience mild cognitive disorders ranging from impaired attention to difficulties in remembering recent events. Despite their negative impact on well-being, these symptoms of sickness are usually ignored. They are viewed as uncomfortable but banal components of infections 1 .Sickness is a normal response to infection, just as fear is normal in the face of a predator. It is characterized by endocrine, autonomic and behavioural changes and is triggered by soluble mediators that are produced at the site of infection by activated accessory immune cells. These mediators are known as pro-inflammatory cytokines, and include interleukin-1α and β (IL-1α and IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). They coordinate the local and systemic inflammatory response to microbial pathogens. However, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript these peripherally produced cytokines also act on the brain to cause the aforementioned behavioural symptoms of sickness. Recently, it has been suggested that 'sickness behaviour' 2, 3, a term used to describe the drastic changes in subjective experience and behaviour that occur in physically ill patients and animals, is an expression of a previously unrecognized motivational state. It is responsible for re-organizing perceptions and actions to enable ill individuals to cope better with an infection4.During the last five years, it has been established that pro-inflammatory cytokines induce not only symptoms of sickness, but also true major depressive disorders in physically ill patients with no previous history of mental disorders. Some of the mechanisms that might be responsible for inflammation-mediated sickness and depression have now been elucidated. These findings suggest that the brain-cytokine system, which is in essence a diffuse system, is the unsuspected conductor of the ensemble of neuronal circuits and neurotransmitters that organize physiologi...

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Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior

Cited by 157 publications

References 72 publications

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Gender and the hygiene hypothesis

From inflammation to sickness and depression: when the immune system subjugates the brain

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