Biology subjects

Mosienko, V.

Publications and source records attributed to Mosienko, V..

4 recordsLinked to original sources

bioRxiv2026

Minocycline engages microglia in the midbrain periaqueductal grey to attenuate hypoxia-triggered panic-like behaviour in rats

Panic disorder (PD) is a chronic and highly disabling psychiatric disorder characterised by recurrent and unexpected panic attacks, with underlying neurobiological mechanisms poorly understood. Emerging evidence suggests that inflammatory processes may contribute to the triggering of panic attacks, with a subset of PD patients exhibiting alterations in circulating cytokine levels, while animal studies indicate that an immunoresponsive microglial phenotype may contribute to the disorders pathophysiology. Minocycline, a tetracycline-class antibiotic that crosses the blood-brain barrier, exerts anti-inflammatory effects and has demonstrated therapeutic potential in attenuating panic attacks, supporting its potential as an alternative strategy for reducing PD-related symptoms by modulating microglial activity. In this study, we investigated whether exposure of male Sprague-Dawley rats to a panicogenic stimulus, hypoxia (7% O2), is followed by microglial morphological remodelling in the midbrain periaqueductal grey (PAG), a well-known panic-associated structure, at baseline and after minocycline treatment. The effects of hypoxia on the expression of panic-like jumping behaviour were measured during the respiratory challenge, whereas microglial morphology was assessed at 1, 6, or 24h following the aversive stimulus. In a second experiment, the effects of minocycline (30 mg/kg, i.p., administered once daily for 5 days) on the immediate behavioural responses to hypoxia were compared with those produced by an acute administration of alprazolam (2 mg/kg, i.p.), a benzodiazepine widely used in the clinical management of PD. Minocycline effects on microglial morphology in the PAG were also assessed. Our findings show that hypoxia elicited robust jumping behaviour, without affecting overall locomotion. This panicogenic effect was accompanied by marked and time-dependent microglial morphological changes in the dorsomedial (dmPAG) and ventrolateral (vlPAG) columns of the PAG, consistent with a shift towards an immunoresponsive phenotype. Notably, minocycline, similarly to alprazolam, reduced the number of jumps, indicating a panicolytic effect, while also preventing hypoxia-induced microglial remodelling in the dmPAG. Altogether, these findings suggest a role for microglia in regulating hypoxia-induced panic- like behaviour, indicating that microglial inhibition, as achieved here with minocycline, represents a promising therapeutic strategy for preventing panic attacks.

neuroscience↗

bioRxiv2026

Caloric restriction and intermittent fasting during lactation are linked to impaired maternal care, increased impulsivity and amygdala redox imbalance in dams

The lactational period requires substantial metabolic and behavioral adaptations, and more than 70% of mothers report weight concerns and attempt weight loss by four months postpartum. Nevertheless, how distinct restrictive paradigms during lactation alter maternal behavior, and the extent to which associated neurochemical changes modulate these behaviors, remains poorly understood. In the current study, we modeled restrictive diets in lactating rats to evaluate caregiving behavior and its relationship to amygdalar redox status. Intermittent fasting (IF) and caloric restriction (CR) administered to lactating Wistar dams from postpartum day 0 to day 28 impaired maternal care, evidenced by delayed pup retrieval, reduced nest building, and decreased nursing frequency relative to ad libitum-fed controls. Both diets reduced body and adipose tissue weight, and energy efficiency. IF and CR increased impulsivity-like phenotype: CR doubled open-arm exploration in the elevated plus maze; IF and CR increased center-zone exploration in the open field by three- and two-fold, respectively; IF doubled time in the light-dark box light compartment. A composite maternal behavioral score showed impairment in dams in both IF and CR groups. At the neurochemical level, both diets reduced amygdalar superoxide dismutase activity, which correlated negatively with the maternal behavioral score. Both restrictive diets produced an underweight phenotype with weakened dam-pup interactions and increased impulsivity. These behavioral changes co-occurred with amygdalar redox imbalance, which correlated with the severity of maternal impairment. Overall, the study refines understanding of the nutritional and behavioral consequences of dietary restriction in lactation and implicates disrupted redox homeostasis as a plausible mechanism.

neuroscience↗

bioRxiv2026

Antidepressant fluoxetine engages astrocytic cAMP via purinergic signalling

The use of selective serotonin reuptake inhibitors (SSRIs), the first-line treatment for depression, has increased by about 50% over the past decade, placing them amongst the top 10 most frequently prescribed drug classes globally. Overall, SSRIs are effective in reducing frequency, severity, and duration of depressive episodes for a majority of patients, yet the mechanisms underlying their therapeutic effects are not fully understood. While SSRIs elevate synaptic serotonin, this action alone cannot account for their therapeutic effects. Additionally, SSRIs engage astrocytes, enhancing cyclic adenosine monophosphate (cAMP) signalling which is reported to be downregulated in depression. However, the signalling mechanisms underlying SSRI-induced upregulation of the astrocytic cAMP pathway remain unclear. Here, we identify a cascade of events by which the SSRI fluoxetine elevates intracellular cAMP levels in astrocytes, a process that depends on astrocyte-microglia crosstalk and purinergic signalling. Using FRET-based sensors in primary rat astrocytes, we show that fluoxetine elevates intracellular cAMP by 28% without altering calcium dynamics. cAMP increase was blocked by both serotonin (5-HT) 2B and adenosine 2B (A2B) receptor antagonists. Using the GRAB-ATP1.0 sensor and luminescence assays, we revealed that fluoxetine enhances astrocytic ATP release by 10% in a 5-HT2B receptor-dependent manner. Consistent with microglia-driven conversion of extracellular ATP to adenosine, which engages astrocytic A2B receptors, depletion of microglia in astrocyte cultures diminished fluoxetine-induced cAMP elevations and increased extracellular ATP. Together, these findings reveal that fluoxetine requires glial crosstalk and coordinated purinergic signalling to enhance astrocytic cAMP, a process shown to contribute to the therapeutic effect of SSRIs.

neuroscience↗

bioRxiv2024

Serotonin drives aggression and social behaviours of laboratory mice in a semi-natural environment

Aggression is an adaptive social behaviour crucial for the stability and prosperity of social groups. When uncontrolled, aggression leads to pathological violence that disrupts group structure and individual well-being. The comorbidity of uncontrolled aggression across different psychopathologies makes it a potential endophenotype of mental disorders with the same neurobiological substrates. Serotonin plays a critical role in the regulation of impulsive and aggressive behaviours, and mice lacking brain serotonin, due to the ablation of a rate-limiting enzyme of serotonin synthesis (Tryptophan hydroxylase 2, TPH2), are a potential model of pathological aggression. Home cage monitoring allows for the continuous observation and quantification of social and non-social behaviours in group-housed, freely-moving mice. Using an ethological approach, we investigated the impact of central serotonin ablation on everyday expression of social and non-social behaviours and their correlations in undisturbed, group-living Tph2-deficient and wildtype mice. By training a machine learning algorithm on behavioural time series, "allogrooming", "struggling at feeder" and "eating" emerged as key behaviours dissociating one genotype from the other. Although Tph2-deficient mice showed characteristics of pathological aggression and decreased communication compared to wildtype animals they still showed affiliative behaviours to normal levels. Altogether, such distinct and dynamic phenotype of Tph2-deficient mice influenced the groups structure and the dynamic of its hierarchical organization which emerged later. These aspects were analyzed using social network analysis and the Glicko rating methods. This study demonstrates the importance of the ethological approach for understanding the global impact of pathological aggression on different aspects of life both at the individual and the group level. Home cage monitoring allows the observation of the natural behaviours of the mice in a semi-natural habitat and provides an accurate representation of real-world phenomena and pathological mechanisms. The results of this study provide insights into the neurobiological substrate of pathological aggression and their potential role in complex brain disorders.

neuroscience↗