Biology subjects

Koskinen, M.-K.

Publications and source records attributed to Koskinen, M.-K..

3 recordsLinked to original sources

bioRxiv2026

Flavonoid chronotherapy normalizes circadian dynamics and sleep architecture in mice with painful nerve injury

Neuropathic pain (NP) is linked to disrupted sleep and circadian abnormalities upon painful peripheral nerve injury. By performing spared nerve injury (SNI) in circadian reporter PER2::LUC mice, we characterized the real-time changes in rhythmicity of the core clock gene Per2 in the pain-regulating dorsal root ganglia (DRG), and the sleep-wake cycle using wireless EEG/EMG under NP conditions. We further evaluated whether the clock-resynchronizing flavonoids, nobiletin (2 mg/kg/day) and tangeretin (1.8 mg/kg/day), administered continuously via osmotic minipumps for two weeks, could restore circadian dynamics and alleviate pain-related behaviour. Both flavonoids alleviated SNI-induced dynamic hypersensitivity in PER2::LUC mice on post-surgical day 14. SNI increased the amplitude of Per2 rhythms in the DRGs, which was restored to pre-surgical levels by administration of flavonoids. In addition, tangeretin showed sleep-restoring properties upon SNI by alleviating disturbances in NREM sleep and wakefulness. These results support targeting circadian disruption as a potential chronotherapeutic approach to alleviate NP.

neuroscience↗

bioRxiv2022

Mind the gap: Nodes of Ranvier are remodeled by chronic psychosocial stress and neuronal activity

Differential expression of myelin-related genes and changes in myelin thickness have been demonstrated in mice after chronic psychosocial stress, a risk factor for anxiety disorders. To determine whether and how stress affects structural remodeling of nodes of Ranvier, another form of myelin plasticity, we developed a 3D reconstruction analysis of node morphology in C57BL/6NCrl and DBA/2NCrl mice. We identified strain-dependent effects of chronic stress on node morphology, including elongation of paranodes in the medial prefrontal cortex (mPFC) in DBA/2NCrl mice. Furthermore, chronic chemogenetic activation of the ventral hippocampus-to-mPFC pathway resulted in increased risk assessment behavior and shortened paranodes specifically in stimulated axons, providing a direct link between anxiety-like behavior and remodeling of the nodes. Altogether, our data demonstrate genetic regulation of nodal remodeling in stress and suggest an activity-dependent regulation of paranodes in anxiety-related circuits. Nodal remodeling may thus contribute to the aberrant circuit function associated with anxiety disorders.

neuroscience↗

bioRxiv2019

From stress to depression: Development of extracellular matrix-dependent cognitive impairment following social stress

Stress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. To shed light on this stress-to-depression transition process, we profiled the development of an enduring depressive-like state in rat by assessing affective behavior and hippocampal function during the 2 months following social defeat stress. In addition, we measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM changes to mediate cognitive impairment during a sustained depressive-like state. We found affective disturbance and cognitive impairment to develop disparately after social stress. While affective deficits emerged gradually, spatial memory impairment was present both early after stress and during the late-emerging chronic depressive-like state. Surprisingly, these phases were separated by a period of normalized hippocampal function. Similarly, the SDPS paradigm induced a biphasic regulation of the hippocampal ECM coinciding with hippocampus-dependent memory deficits. Early after stress, synaptic ECM proteins and the number of perineuronal nets enwrapping parvalbumin-expressing interneurons were decreased. This was followed by a recovery period without ECM dysregulation, before subsequent decreased metalloproteinase activity and ECM build-up, previously shown to impair memory. This suggests that intact hippocampal function requires unaltered ECM levels. Together our data 1) reveal a dichotomy between affective and cognitive impairments similar to that observed in patients, 2) indicate different molecular processes taking place during early stress and the chronic depressive-like state, and 3) support a role of the ECM in mediating long-lasting memory-effects of social stress.

neuroscience↗