Biology subjects

Mihaljevic, M.

Publications and source records attributed to Mihaljevic, M..

7 recordsLinked to original sources

bioRxiv2024

Amyloid Beta Precursor Protein contributes to brain aging and learning decline in short-lived turquoise killifish (Nothobranchius furzeri)

Brain aging is a key risk factor for many neurodegenerative diseases, yet its molecular and cellular mechanisms remain elusive. Amyloid-beta precursor protein (APP) is among the most studied proteins linked to brain pathology; however, its role in non-pathological brain aging remains poorly characterized. Here, we investigate the natural impact of APP on normal brain aging using the short-lived turquoise killifish (Nothobranchius furzeri), which exhibits rapid and spontaneous age-related decline. We found that a pyroglutamated APP derivative (APPpE11) accumulates intra-neuronally in an age-dependent manner, co-localizing with a marker of cell death. We found that intraneuronal APPpE11 is also present in brains from healthy elderly humans, suggesting deep evolutionary conservation. To determine APPs role in spontaneous brain aging, we knock-out "amyloid precursor protein a" (appa) in killifish via CRISPR/Cas9. The lack of appa mitigated brain aging from a proteome-wide perspective, reduced age-related cell death and inflammation, and improved neuronal activity and learning capacity in aged individuals. Our findings show an ancestral and previously unrecognized role of amyloid-beta precursor protein in non-pathological brain aging, making it an ideal target for anti-aging interventions.

neuroscience↗

bioRxiv2021

Neuroimaging signature associated with symptom exacerbation in early-stage psychosis

Recent reports have indicated that the occurrence of symptom exacerbation in early-stage psychosis could result in brain changes. Such a symptom exacerbation is frequently called relapse, which underlies a poorer disease outcome. Thus, it is important to identify neuroimaging alterations that are specifically seen in patients who experience relapse in early-stage psychosis. We hypothesized that this specific patient group may be more homogenous in disease-associated signatures likely to be linked to relapse, compared with the overall patient group. Such sub-stratified patient group and neuroimaging signatures would be useful for the biological understanding of relapse. To address this goal, we conducted a cross-sectional study (85 patients with early-stage psychosis and 94 healthy controls) with the use of medical records in a retrospective manner. To define the specific sub-group with the past experience of relapse, we used hospitalization due to psychotic symptom exacerbation, according to many publications that used this factor as a proxy for relapse. By examining resting-state functional connectivity (FC) for the study subjects, we validated our hypothesis and defined 131 FCs possibly associated with relapse. Through these studies, 3 brain regions (the thalamus, precentral gyrus, and dorsal anterior cingulate cortex) were underscored.

neuroscience↗

bioRxiv2021

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy, from a first episode psychosis cohort that includes 138 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a significant reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a significant reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC GSH, HP and SFG volumes, and age at onset could potentially be trait biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

neuroscience↗

bioRxiv2021

Face processing of social cognition in patients with first episode psychosis: Its deficits and association with the right subcallosal anterior cingulate cortex

The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 79 FEP patients and 80 healthy controls (HCs). We looked for a possible correlation between face processing and multimodal MRI characteristics such as resting-state functional connectivity (rsFC) and brain volume. We observed worse recognition accuracy, longer recognition response time, and longer memory response time in FEP patients when compared with HCs. Of these, memory response time was selectively correlated with specific rsFCs, which included the right subcallosal sub-region of BA24 in the ACC (scACC), only in FEP patients. The volume of this region was also correlated with memory response time in FEP patients. The scACC is functionally and structurally important in FEP-associated abnormalities of face processing measures in social cognition.

neuroscience↗

bioRxiv2021

Anterior insula-associated social novelty recognition: orchestrated regulation by a local retinoic acid cascade and oxytocin signaling

BackgroundDeficits in social cognition consistently underlie functional disabilities in a wide range of psychiatric disorders. Neuroimaging studies have suggested that the anterior insula is a common core brain region that is impaired across neurological and psychiatric disorders, which include social cognition deficits. Nevertheless, neurobiological mechanisms of the anterior insula for social cognition remain elusive. MethodsTo determine the role of anterior insula in social cognition, we manipulated expression of Cyp26B1, an anterior insula-enriched molecule that is crucial for retinoic acid degradation and involved in the pathology of neuropsychiatric conditions. Social cognition was mainly assayed using the three-chamber social interaction test. We conducted multimodal analyses at the molecular, cellular, circuitry, and behavioral levels. ResultsAt the molecular/cellular level, anterior insula-mediated social novelty recognition is maintained by proper activity of the layer 5 pyramidal neurons, for which retinoic acid-mediated gene transcription can play a role. We also demonstrate that oxytocin influences the anterior insula-mediated social novelty recognition, not by direct projection of oxytocin neurons, nor by direct diffusion of oxytocin to the anterior insula, which contrasts the modes of oxytocin regulation onto the posterior insula. Instead, oxytocin affects oxytocin receptor-expressing neurons in the dorsal raphe nucleus where serotonergic neurons are projected to the anterior insula. Furthermore, we show that serotonin 5HT2C receptor expressed in the anterior insula influences social novelty recognition. ConclusionsAnterior insula plays a pivotal role in social novelty recognition that is partly regulated by a local retinoic acid cascade, but also remotely regulated by oxytocin via a non-classic mechanism.

animal behavior and cognition↗

bioRxiv2020

Cryptic diversity masks ecologically distinct coral species on tropical reefs

Coral reefs are the epitome of species diversity, yet the number of described scleractinian coral species, the framework-builders of coral reefs, remains moderate by comparison. DNA sequencing studies are rapidly challenging this notion by exposing a wealth of undescribed diversity, but the evolutionary and ecological significance of this diversity remains largely unclear. Here, we present an annotated genome for one of the most ubiquitous corals in the Indo-Pacific (Pachyseris speciosa), and uncover through a comprehensive genomic and phenotypic assessment that it comprises morphologically indistinguishable, but ecologically divergent cryptic lineages. Demographic modelling based on whole-genome resequencing disproved that morphological crypsis was due to recent divergence, and instead indicated ancient morphological stasis. Although the lineages occur sympatrically across shallow and mesophotic habitats, extensive genotyping using a rapid diagnostic assay revealed differentiation of their ecological distributions. Leveraging "common garden" conditions facilitated by the overlapping distributions, we assessed physiological and quantitative skeletal traits and demonstrated concurrent phenotypic differentiation. Lastly, spawning observations of genotyped colonies highlighted the potential role of temporal reproductive isolation in the limited admixture, with consistent genomic signatures in genes related to morphogenesis and reproduction. Overall, our findings demonstrate how ecologically and phenotypically divergent coral species can evolve despite morphological stasis, and provide new leads into the potential mechanisms facilitating such divergence in sympatry. More broadly, they indicate that our current taxonomic framework for reef-building corals may be scratching the surface of the ecologically relevant diversity on coral reefs, consequently limiting our ability to protect or restore this diversity effectively.

evolutionary biology↗

bioRxiv2019

Citizen scientists highlight conservation value of a small subtropical reef, Flinders Reef, southeast Queensland, Australia.

Subtropical reefs are unique ecosystems that require effective management - informed by regular ecological monitoring - to foster resilience to environmental changes. Resources to conduct monitoring are limited, and citizen science can complement data from local management agencies. Here, citizen science efforts document the ecological status of a subtropical reef, Flinders Reef, Moreton Bay Marine Park, Australia. Ecological surveys, following Reef Check Australia and CoralWatch protocols, were conducted by 44 trained volunteers. Ten sites at Flinders Reef were surveyed at 5-10 m depth in autumn and spring. Additionally, underwater photos and depth surveys were integrated with satellite imagery to create a detailed habitat map. Coral cover across sites ranged between 14% and 67%. Branching corals dominated the site with 67% cover and showed 89% dissimilarity in coral community composition compared to other sites. Coral community composition was mostly explained by spatial variation, of which 16% was influenced by wave exposure. Observed reef impacts including physical damage, unknown scars and coral disease were three times lower than studies on more accessible reefs in Moreton Bay Marine Park. Invertebrate abundance was relatively low (6.65 individuals per 100 m2), with the most abundant groups observed being sea urchins (Diadema spp.), gastropods (Drupella spp.) and anemones. Butterflyfish were recorded at every site and were the most abundant fish group surveyed. Findings highlight the healthy condition of Flinders Reef, likely influenced by its offshore location and protection status as a no-take zone. This study demonstrates that increasing the current 500m radius protection zone by a further 500m could double the protected area of coral, offering potential further conservation benefits. The findings resulting from the ecological data analysis and created benthic habitat map, provide an example of how citizen science based projects can assist marine park authorities and the public in ongoing conservation efforts.

ecology↗