Biology subjects

Shonka, S.

Publications and source records attributed to Shonka, S..

3 recordsLinked to original sources

bioRxiv2025

Impact of Dysbiosis and Antiseizure Medication on Seizure Pathophysiology in a Viral Infection-Induced Epilepsy Model

Viral encephalitis is a major worldwide cause of acquired epilepsy, yet the impact of environmental and non-neuronal factors on an individuals risk for epilepsy is understudied. For example, the gut microbiome influences immune system function yet the impact of the gut microbiome on seizure-associated neuropathology remains poorly understood. Using the Theilers murine encephalomyelitis virus (TMEV) mouse model of infection-induced acute symptomatic seizures (ASyS), we aimed to investigate how antibiotic (ABX)-induced gut dysbiosis during a brain viral infection could influence resulting hippocampal neuropathology. Further, we included co-administration of carbamazepine (CBZ) to assess the extent to which antiseizure medicines could also shift the neurological impact of ASyS and gut dysbiosis. Brain tissue from TMEV-infected mice with and without gut dysbiosis was assessed for neurodegeneration and glial response (astrocytes and microglia). TMEV infection primarily drove neuroinflammatory changes in CA1, including increased astrogliosis, microgliosis, and microglial activation. ABX-induced dysbiosis exacerbated neuroinflammation across hippocampal subregions, markedly increasing microgliosis in CA3 and DG, and elevating microglial and neuronal proliferation in CA1. TMEV infection-induced astrogliosis was impacted by dysbiosis in a region-dependent manner, being worsened in DG while being alleviated in CA3. CBZ was neuroprotective selectively within DG, reducing neurodegeneration and microglial immunoreactivity with dysbiosis. Astroglial proliferation occurred regardless of gut microbiome integrity. Altogether, gut dysbiosis shapes hippocampal neuroimmune responses following viral infection-induced ASyS in a region-dependent manner, and CBZ may confer a neuroprotective effect. Together this work highlights the acute neuroinflammatory impact of infection-induced ASyS and reveals an underappreciated contribution of the gut-brain-axis to seizure-related neuropathology.

neuroscience↗

bioRxiv2025

Younger is Better But Only for Males: Social Behavioral Development Following Juvenile Traumatic Brain Injury to the Prefrontal Cortex

Juvenile traumatic brain injury (jTBI) is associated with persistent social impairments, particularly when injury occurs early in development. The prefrontal cortex (PFC) is especially vulnerable to injury due to its late maturation and location, and developmental disruptions during key phases such as synaptic pruning or myelination may result in long-term behavioral deficits. This study investigated how the age at injury and biological sex influenced the development of social behavior and frontal cortical plasticity. Using a controlled cortical impact model of a bilateral medial PFC (mPFC) injury, we compared injuries sustained on postnatal day (PND) 17 or 28--approximating toddlerhood and middle childhood, respectively. Social behaviors were assessed longitudinally during pre-puberty, puberty, and young adulthood. Play behavior, sociability, social memory, social dominance, and aggression were evaluated, and morphological analyses examined dendritic complexity in the orbitofrontal cortex (OFC) and mPFC using Golgi-Cox staining, and myelin integrity across the mPFC-OFC-amygdala circuit using Luxol-fast blue staining. We hypothesized that PND 17 injuries would result in greater social deficits and increased aggression compared to PND 28 injuries and shams, with males showing more severe impairments than females. Results partially supported these predictions. While jTBI had no effect on general play engagement, it did alter play initiation: PND 28 injury increased play initiation in both sexes, while PND 17 TBI injury delayed normal play development in females. Injuries had no significant impact on sociability or social memory. However, PND 28 injury increased social dominance and aggression in adulthood, with sex moderating these effects. Specifically, PND 17 injury decreased aggression in males and increased it in females. Childhood play behaviors predicted adult aggression, particularly in PND 28-injured animals, and these relationships were moderated by injury and sex. Despite the behavioral findings, histological analyses revealed no significant group differences in dendritic complexity or myelination, though effect sizes suggested decreased dendritic arborization and increased myelin in PND 28-injured animals. These findings highlight age- and sex-dependent vulnerability in the development of social behavior following jTBI. Contrary to expectations, early injury had more pronounced effects in females, while later injury was more detrimental for males. The divergence in behavioral outcomes despite limited histological differences suggests complex, possibly circuit-specific, mechanisms underlying these effects. This study underscores the importance of considering both sex and developmental timing in jTBI research and supports the need for longitudinal models to capture evolving behavioral trajectories.

animal behavior and cognition↗

bioRxiv2025

Acute Administration of Oxytocin in the Functional Recovery of Neurocognitive and Social Deficits Following Juvenile Frontal Traumatic Brain Injury

IntroductionJuvenile traumatic brain injury (jTBI) is one of the leading causes of death and disability in children. The prefrontal cortex (PFC) is most susceptible to injury which leads to deficits in executive function, social behaviors, and cognitive flexibility. Prior research has shown a significant role of the oxytocin (OXT) system in the modulation of social behaviors, and that intranasal OXT (IN-OXT) is potentially neuroprotective. Therefore, we believe IN-OXT could improve functional recovery from a PFC injury. MethodsAnimals received a single midline cortical contusion bilaterally damaging the medial PFC (mPFC) and immediately given a single dose of IN-OXT, placebo, or no treatment. Animals were assessed using behavioral and histological measures. ResultsThe results indicated that jTBI significantly impacted the normal development of the OXT system, likely due to deficits in OXT synthesis in the SON. While IN-OXT alleviated these deficits, it had no impact on neuroinflammation. Similarly, behavioral effects of IN-OXT were not consistent. Mild improvements were observed in spatial learning but there were no improvements in spatial memory or social dominance. DiscussionThese results show that IN-OXT increases OXT levels in the brain via pathways originating in the SON and improved spatial learning.

neuroscience↗