Gut-brain axis: gut dysbiosis and psychiatric disorders in Alzheimer's and Parkinson's disease.

Gut dysbiosis and psychiatric symptoms are common early manifestations of Alzheimer's disease (AD) and Parkinson's disease (PD). These diseases, characterised by progressive neuron loss and pathological protein accumulation, impose debilitating effects on patients. Recently, these pathological proteins have been linked with gut dysbiosis and psychiatric disorders. The gut-brain axis links the enteric and central nervous systems, acting as a bidirectional communication pathway to influence brain function and behavior. The relationship triad between gut dysbiosis, psychiatric disorders, and neurodegeneration has been investigated in pairs; however, evidence suggests that they are all interrelated and a deeper understanding is required to unravel the nuances of neurodegenerative diseases. Therefore, this review aims to summarise the current literature on the roles of gut dysbiosis and psychiatric disorders in pathological protein-related neurodegenerative diseases. We discussed how changes in the gut environment can influence the development of psychiatric symptoms and the progression of neurodegeneration and how these features overlap in AD and PD. Moreover, research on the interplay between gut dysbiosis, psychiatric disorders, and neurodegeneration remains in its early phase. In this review, we highlighted potential therapeutic approaches aimed at mitigating gastrointestinal problems and psychiatric disorders to alter the rate of neurodegeneration. Further research to assess the molecular mechanisms underlying AD and PD pathogenesis remains crucial for developing more effective treatments and achieving earlier diagnoses. Moreover, exploring non-invasive, early preventive measures and interventions is a relatively unexplored but important avenue of research in neurodegenerative diseases.

Generation of a human embryonic stem cell reporter line, TMEM119-EGFP, for the visualisation of in vitro differentiated human microglia.

Transmembrane protein 119 (TMEM119) is a recently identified microglia marker that is not expressed by other immune cells. Using CRISPR/Cas9 technology, we introduced enhanced green fluorescence protein (EGFP), into the H9 WA-09 human embryonic stem cell line, directly before the TMEM119 stop codon. Sanger sequencing confirmed successful insertion of the EGFP sequence. The newly created cell line expressed a normal morphology and karyotype, several pluripotency markers, and the ability to differentiate into all three germ layers. H9-TMEM119-EGFP can be used to provide a deeper understanding of the role of TMEM119 in microglia by monitoring its expression under different experimental conditions.

An update on the rod microglia variant in experimental and clinical brain injury and disease.

Contemporary microglia morphologies include ramified, activated and amoeboid, with the morphology of microglia considered highly coupled to the cellular function. Rod microglia are an additional activated microglia variant observed in the ageing, injured and diseased brain. Rod microglia were reported frequently in the early 1900s by neuropathologists in post-mortem cases of general paresis, Alzheimer's disease and encephalitis, and then remained largely ignored for almost 100 years. Recent reports have renewed interest in rod microglia, most notably after experimental traumatic brain injury. Rod microglia are formed by the narrowing of the soma and retraction of planar processes, which results in the appearance of an elongated, rod-shaped cell. Rod microglia are most commonly observed in the cortex, aligned perpendicular to the dural surface and adjacent to neuronal processes; in the hippocampus, they are aligned perpendicular to hippocampal layers. Furthermore, rod microglia form trains with one another, apical end to basal end. By replicating the process of sketching microscopic observation, rod microglia are re-defined by circumnutation around the long axis. In this update, we summarize the rod microglia variant in clinical and experimental literature and advocate for investigation into mechanisms of rod microglia origin and function.

Intracerebral hemorrhage in the mouse altered sleep-wake patterns and activated microglia.

Sleep-wake disturbances are both a risk factor and reported morbidity for intracerebral hemorrhage (ICH). ICH begins with a ruptured blood vessel and blood leakage into the parenchyma. In response to initial damage, pathophysiological processes ensue that both exacerbate and repair damage. Inflammation is a hallmark process of ICH, which includes microglia activation and increased cytokine signaling. Due to the dual role of cytokines as inflammatory signaling proteins and sleep regulatory substances (SRSs), we hypothesized that ICH would activate microglia, increase SRSs, and alter sleep-wake patterns following an experimental model of ICH in the mouse. Male mice were randomized to receive an injection of collagenase (ICH; n = 8) or saline (sham; n = 11) in the striatum of the right hemisphere. Sleep-wake activity was recorded for 6 full days after ICH via noninvasive sleep cages. Blood and tissue were collected at 7 days after ICH to quantify pro-inflammatory cytokines/SRSs (IL-1ß, TNF-α, IL-6) and microglia deramification by skeleton analysis. There was an overall injury effect on sleep in mice subjected to ICH at the transition from dark (wake) to light (sleep) at 2, 3, 4, 5, and 6 days after ICH compared with shams. Further analysis confirmed that ICH mice had significantly earlier wake offsets at the dark/light transition and more robust circadian patterns of wake behavior than saline control mice. Spatiotemporal skeleton analysis indicated an increase in microglial cell number with a decrease in endpoints per cell (decreased ramification) for the ipsilateral ICH perihematomal region compared with saline control. There were no changes to plasma cytokine levels at 7 days after ICH when comparing each condition. This is the first known study to show changes in sleep-wake patterns after experimental ICH. Elucidation of mechanisms that link sleep, inflammation, and ICH offers new pharmacological opportunities and rehabilitative strategies to improve recovery in stroke patients.