Dysregulated placental expression of kynurenine pathway enzymes is associated with inflammation and depression in pregnancy.

Background: Perinatal depression (including antenatal-, postnatal-, and depression that spans both timepoints) is a prevalent disorder with high morbidity that affects both mother and child. Even though the full biological blueprints of perinatal depression remain incomplete, multiple studies indicate that, at least for antenatal depression, the disorder has an inflammatory component likely linked to a dysregulation of the enzymatic kynurenine pathway. The production of neuroactive metabolites in this pathway, including quinolinic acid (QUIN), is upregulated in the placenta due to the multiple immunological roles of the metabolites during pregnancy.

Urinary tract infections trigger synucleinopathy via the innate immune response.

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also be important triggers of MSA.

IL-10: A possible immunobiological component of positive mental health in refugees.

Objective: As the number of refugees continues to rise, there is growing concern about the impact from trauma exposures on their mental health. However, there is a limited understanding of possible biological mechanisms contributing to the substantial inter-individual differences in trauma-related outcomes, especially as it relates to positive mental health. Only sparse work has focused on the biology of positive mental health, including energy and sleep, in trauma-exposed persons.

Bacterial Butyrate in Parkinson's Disease Is Linked to Epigenetic Changes and Depressive Symptoms.

Background: The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers.

Objectives: Here, we investigate whether the changes in the gut microbiome and associated metabolites are related to PD symptoms and epigenetic markers in leucocytes and neurons.

Maternal Herpesviridae infection during pregnancy alters midbrain dopaminergic signatures in adult offspring.

Background: Motor symptoms of Parkinson's disease (PD) are apparent after a high proportion of dopamine neurons in the substantia nigra have degenerated. The vast majority of PD cases are sporadic, and the underlying pathobiological causes are poorly understood. Adults exhibit great variability in the numbers of nigral dopamine neurons, suggesting that factors during embryonic or early life regulate the development and physiology of dopaminergic neurons.

Cytokine and Reward Circuitry Relationships in Treatment-Resistant Depression.

Background: Depressive disorders are linked to dysfunction in reward-related behaviors and corticostriatal reward circuitry. Low-grade dysregulation of the immune system, e.g.

Upregulation of α-synuclein following immune activation: Possible trigger of Parkinson's disease.

Alpha-synuclein (α-syn) has been suggested to have many functions including, vesicle transport in neurons, transcriptional regulator, modulator of immune cell maturation and response, and a role as an antimicrobial peptide. This protein forms insoluble aggregates, called Lewy bodies, in several neurodegenerative diseases, termed synucleinopathies, including Parkinson's disease (PD), Multiple System Atrophy, and Lewy Body Dementia, and aggregates are also commonly found in Alzheimer's disease. Moreover, multiplications and point mutations in the gene cause rare autosomal dominant forms of parkinsonism, which resemble sporadic PD.

Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy.

Depression during and after pregnancy affects up to 20% of pregnant women, but the biological underpinnings remain incompletely understood. As pregnancy progresses, the immune system changes to facilitate fetal development, leading to distinct fluctuations in the production of pro-inflammatory factors and neuroactive tryptophan metabolites throughout the peripartum period. Therefore, it is possible that depression in pregnancy could constitute a specific type of inflammation-induced depression.

Digesting recent findings: gut alpha-synuclein, microbiome changes in Parkinson's disease.

Two hallmarks of Parkinson's disease (PD) are the widespread deposition of misfolded alpha-synuclein (αSyn) protein in the nervous system and loss of substantia nigra dopamine neurons. Recent research has suggested that αSyn aggregates in the enteric nervous system (ENS) lead to prodromal gastrointestinal (GI) symptoms such as constipation in PD, then propagating to the brain stem and eventually triggering neurodegeneration and motor symptoms. Additionally, whether the microbiome changes in PD contribute to the primary pathogenesis or, alternatively, are consequential to either the disease process or medication is still unclear.

Physical Activity Is Associated With Lower Long-Term Incidence of Anxiety in a Population-Based, Large-Scale Study.

Physical activity may prevent anxiety, but the importance of exercise intensity, sex-specific mechanisms, and duration of the effects remains largely unknown. We used an observational study design to follow 395,369 individuals for up to 21 years to investigate if participation in an ultralong-distance cross-country ski race (Vasaloppet, up to 90 km) was associated with a lower risk of developing anxiety. Skiers in the race and matched non-skiers from the general population were studied after participation in the race using the Swedish population and patient registries.

Decreased Risk of Parkinson's Disease After Rheumatoid Arthritis Diagnosis: A Nested Case-Control Study with Matched Cases and Controls.

Background: Rheumatoid arthritis (RA) and the genetic risk landscape of autoimmune disorders and Parkinson's disease (PD) overlap. Additionally, anti-inflammatory medications used to treat RA might influence PD risk.

Objective: To use a population-based approach to determine if there is an association between pre-occurring rheumatoid arthritis (RA) and later-life risk of PD.

T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils.

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α-synucleinopathies, such as Parkinson's disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system.

Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson's Disease.

The gut microbiome can impact brain health and is altered in Parkinson's disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alterations.

Quantification of Plasma Kynurenine Metabolites Following One Bout of Sprint Interval Exercise.

The kynurenine pathway of tryptophan degradation produces several neuroactive metabolites suggested to be involved in a wide variety of diseases and disorders, however, technical challenges in reliably detecting these metabolites hampers cross-comparisons. The main objective of this study was to develop an accurate, robust and precise bioanalytical method for simultaneous quantification of ten plasma kynurenine metabolites. As a secondary aim, we applied this method on blood samples taken from healthy subjects conducting 1 session of sprint interval exercise (SIE).

Tryptophan Metabolites Are Associated With Symptoms and Nigral Pathology in Parkinson's Disease.

Background: The objective of this study was to determine whether neurotoxic kynurenine metabolites, induced by inflammation, in plasma and cerebrospinal fluid (CSF) are associated with symptom severity and nigral pathology in Parkinson's disease (PD).

Methods: Clinical and MRI data were obtained from 97 PD and 89 controls. We used ultra-performance liquid chromatography to quantify kynurenine metabolites and high-sensitivity multiplex assays to quantify inflammation in plasma and CSF.