Noradrenergic Signaling and Neuroinflammation Crosstalk Regulate Toxoplasma gondii-Induced Behavioral Changes

Laing, Conor; Blanchard, Nicolas; McConkey, Glenn A.

doi:10.1016/j.it.2020.10.001

Cited by 19 publications

(12 citation statements)

References 70 publications

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“…It has been proposed that an interplay between neuroinflammation and neurotransmission may underlie cognitive changes associated with chronic toxoplasmosis (160). Indeed, reported neurotransmission alterations during toxoplasmosis in rodents include dysregulations of catecholamines, GABA and glutamate (161)(162)(163).…”

Section: Control Of Infection By Brain Parenchymal Cellsmentioning

confidence: 99%

Neuroimmunology of Common Parasitic Infections in Africa

et al. 2022

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Parasitic infections of the central nervous system are an important cause of morbidity and mortality in Africa. The neurological, cognitive, and psychiatric sequelae of these infections result from a complex interplay between the parasites and the host inflammatory response. Here we review some of the diseases caused by selected parasitic organisms known to infect the nervous system including Plasmodium falciparum, Toxoplasma gondii, Trypanosoma brucei spp., and Taenia solium species. For each parasite, we describe the geographical distribution, prevalence, life cycle, and typical clinical symptoms of infection and pathogenesis. We pay particular attention to how the parasites infect the brain and the interaction between each organism and the host immune system. We describe how an understanding of these processes may guide optimal diagnostic and therapeutic strategies to treat these disorders. Finally, we highlight current gaps in our understanding of disease pathophysiology and call for increased interrogation of these often-neglected disorders of the nervous system.

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Section: Control Of Infection By Brain Parenchymal Cellsmentioning

confidence: 99%

Neuroimmunology of Common Parasitic Infections in Africa

et al. 2022

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“…(C) Laing et al suggest that the elevated pro-inflammatory cytokines can be suppressed and the lack of NE can be compensated for (at least partially) by treating the T. gondii-infected rodents with Guanabenz (a noradrenergic agonist), which has been linked with reversal of T. gondii infection-induced hyperlocomotion in rodents) [Reprinted from (363); Copyright (2020); with permission from Elsevier; License # 4986231317003]. lead to a lower tonic inhibition of excessive neuroinflammation (see Figure 11), ultimately resulting in neuronal damage, changes in brain connectivity and cognitive deficits, thus contributing to the risk for suicidal behavior (122,362,363). Some of the limitations of this study include a crosssectional design, not using standardized structured instruments and collateral information to diagnose depression, and potential underreporting of symptoms of depression due to reporting/recall bias or cultural factors.…”

Section: Relevancementioning

confidence: 99%

Toxoplasma gondii, Suicidal Behavior, and Intermediate Phenotypes for Suicidal Behavior

Postolache

Wadhawan

Rujescu³

et al. 2021

Front. Psychiatry

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Within the general literature on infections and suicidal behavior, studies on Toxoplasma gondii (T. gondii) occupy a central position. This is related to the parasite's neurotropism, high prevalence of chronic infection, as well as specific and non-specific behavioral alterations in rodents that lead to increased risk taking, which are recapitulated in humans by T. gondii's associations with suicidal behavior, as well as trait impulsivity and aggression, mental illness and traffic accidents. This paper is a detailed review of the associations between T. gondii serology and suicidal behavior, a field of study that started 15 years ago with our publication of associations between T. gondii IgG serology and suicidal behavior in persons with mood disorders. This “legacy” article presents, chronologically, our primary studies in individuals with mood disorders and schizophrenia in Germany, recent attempters in Sweden, and in a large cohort of mothers in Denmark. Then, it reviews findings from all three meta-analyses published to date, confirming our reported associations and overall consistent in effect size [ranging between 39 and 57% elevation of odds of suicide attempt in T. gondii immunoglobulin (IgG) positives]. Finally, the article introduces certain links between T. gondii and biomarkers previously associated with suicidal behavior (kynurenines, phenylalanine/tyrosine), intermediate phenotypes of suicidal behavior (impulsivity, aggression) and state-dependent suicide risk factors (hopelessness/dysphoria, sleep impairment). In sum, an abundance of evidence supports a positive link between suicide attempts (but not suicidal ideation) and T. gondii IgG (but not IgM) seropositivity and serointensity. Trait impulsivity and aggression, endophenotypes of suicidal behavior have also been positively associated with T. gondii seropositivity in both the psychiatrically healthy as well as in patients with Intermittent Explosive Disorder. Yet, causality has not been demonstrated. Thus, randomized interventional studies are necessary to advance causal inferences and, if causality is confirmed, to provide hope that an etiological treatment for a distinct subgroup of individuals at an increased risk for suicide could emerge.

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“…Toxoplasma is an intracellular obligate parasitic pathogen that is capable of infecting and replicating within any nucleated mammalian or avian cells (Dubey, 2010) and can even alter the host's behaviour to increase its own transmission (Ferguson, 2009;Laing et al, 2020). T. gondii infects most species of warm-blooded animals, including humans.…”

Section: Life Cycle Of T Gondiimentioning

confidence: 99%

Toxoplasma gondii: Deeper understanding of epidemiology, virulence and pathophysiology enhances diagnosis and informs vaccine design

Woyesa¹,

Taylor‐Robinson²

2021

J. Infect. Dis. Immun.

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Toxoplasma gondii is an extremely widespread intracellular obligate parasite that infects both animals and birds. This protozoan pathogen usually causes asymptomatic infection in humans but can cause significant disease in congenitally infected infants, immunodeficient patients and occasionally in immunocompetent individuals. In the complex life cycle of T. gondii, sexual development occurs uniquely in felines whereas asexual reproduction may take place in humans and other warm-blooded animals serving as intermediate hosts. The prevalence of infection varies considerably among different geographic areas and also among individuals, depending on a variety of factors, including culinary habits and cleanliness of surroundings. Studies to date show low genetic diversity of T. gondii, with three main lineages, designated types I, II and III, found at least within Europe and North America. T. gondii uses various mechanisms to invade host cells and to alter their signal pathways and gene expression. Kinases within the rhoptry, a unique apical organelle, and T. gondii granule proteins are key virulence factors that promote attachment to, and invasion of, host cells. Human Toxoplasma infection is acquired by ingestion of raw or undercooked meat that contains tissue cysts, or through the ingestion of water or food contaminated with oocysts. It is also transmitted congenitally from motherto-foetus and less commonly by transfusion of contaminated blood or transplantation of an infected organ. Life-threatening toxoplasmosis can develop in immunocompromised patients. Diagnostic tests are critical to surveillance, control and prevention of toxoplasmosis. However, different technologies presently utilized around the world to detect different parasite stages are not of a uniformly sufficient standard to indicate clearly the epidemiology and severity of infection at global, regional and national levels. While a prophylactic vaccine is licensed for veterinary administration, no similarly efficacious preparation is available to prevent human infections. Here, we review the epidemiology and genotypes of T. gondii, as well as current detection methods and the state of vaccine development. In addition, the mechanisms by which this parasitic pathogen invades and overcomes the human immune system are considered.

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Noradrenergic Signaling and Neuroinflammation Crosstalk Regulate Toxoplasma gondii-Induced Behavioral Changes

Cited by 19 publications

References 70 publications

Neuroimmunology of Common Parasitic Infections in Africa

Neuroimmunology of Common Parasitic Infections in Africa

Toxoplasma gondii, Suicidal Behavior, and Intermediate Phenotypes for Suicidal Behavior

Toxoplasma gondii: Deeper understanding of epidemiology, virulence and pathophysiology enhances diagnosis and informs vaccine design

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