Probiotic consumption during puberty mitigates LPS-induced immune responses and protects against stress-induced depression- and anxiety-like behaviors in adulthood in a sex-specific manner.

Puberty/adolescence is a significant period of development and a time with a high emergence of psychiatric disorders. During this period, there is increased neuroplasticity and heightened vulnerability to stress and inflammation. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behaviour. However, the role of the gut microbiota during pubertal development remains largely uninvestigated. The current study examined gut manipulation with probiotics during puberty in CD1 mice on lipopolysaccharide (LPS)-induced immune responses and enduring effects on anxiety- and depression-like behaviours and stress-reactivity in adulthood. Probiotics reduced LPS-induced sickness behaviour at 12 h in females and at 48 h following LPS treatment in males. Probiotics also reduced LPS-induced changes in body weight at 48 h post-treatment in females. Probiotic treatment also prevented LPS-induced increases in pro- and anti-inflammatory peripheral cytokines at 8 h following LPS treatment, reduced central cytokine mRNA expression in the hypothalamus, hippocampus and PFC, and prevented LPS-induced changes to in the gut microbiota. A single exposure to LPS during puberty resulted in enduring depression-like behaviour in female mice, and anxiety-like behaviour in male mice in adulthood. However, pubertal exposure to probiotics prevented enduring LPS-induced depression-like behaviour in females and anxiety-like behaviors in males. Moreover, probiotics altered toll-like receptor-4 activity in the paraventricular nucleus of the hypothalamus (PVN) in males in response to a novel stressor in adulthood. Our results suggest that the gut microbiome plays an important role in pubertal neurodevelopment. These findings indicate that exposure to probiotics during puberty mitigates inflammation and decreases stress-induced vulnerabilities to emotional behaviours later in life, in a sex-specific manner.

Environmental enrichment alters LPS-induced changes in BDNF and PSD-95 expressions during puberty.

Puberty is a critical period of cortical reorganization and increased synaptogenesis. Healthy cortical reorganization and synaptic growth require sufficient environmental stimuli and minimalized stress exposure during pubertal development. Exposure to impoverished environments or immune challenges impact cortical reorganization and reduce the expression of proteins associated with neuronal plasticity (BDNF) and synaptogenesis (PSD-95). Environmentally enriched (EE) housing includes improved social-, physical-, and cognitive stimulation. We hypothesized that enriched housing environment would mitigate pubertal stress-induced decreases in BDNF and PSD-95 expressions. Three-week-old male and female CD-1 mice (n = 10 per group) were housed for three weeks in either EE, social or deprived housing conditions. At 6 weeks of age, mice were treated with either lipopolysaccharide (LPS) or saline eight hours prior to tissue collection. Male and female EE mice displayed greater BDNF and PSD-95 expressions in the medial prefrontal cortex and hippocampus compared to socially housed and deprived housed mice. LPS treatment decreased BDNF expression in all the brain regions examined in EE mice, except for the CA3 region of the hippocampus, where EE housing successfully mitigated the pubertal LPS-induced decrease in BDNF expression. Interestingly, LPS-treated mice housed in deprived conditions displayed unexpected increases in BDNF and PSD-95 expressions throughout the medial prefrontal cortex and hippocampus. Both enriched and deprived housing conditions moderate how an immune challenge influences BDNF and PSD-95 expressions in a region-specific manner. These findings also emphasize the vulnerability of brain plasticity during puberty to various environmental factors.

A Randomized Controlled Trial of a Parent-Led Memory-Reframing Intervention to Reduce Distress and Pain Associated with Vaccine Injections in Young Children.

Children remember their memories of pain long after the painful experience is over. Those memories predict higher levels of future pain intensity. Young children's memories can be reframed to be less distressing. Parents and the way they reminisce about past events with their children play a key role in the formation of pain memories. A novel parent-led memory-reframing intervention changed children's memories of post-surgical pain to be less distressing. The intervention efficacy in the context of vaccine injections is unclear. This registered randomized controlled trial (NCT05217563) aimed to fill this gap. Seventy-four children aged 4.49 years (SD = 1.05) and scheduled to obtain two COVID-19 vaccine injections and one of their parents were randomized to receive: (1) standard care; (2) standard care and memory-reframing information; and (3) standard care and memory-reframing information with verbal instructions. Children reported their pain after vaccine injections. One week after the first vaccination, children reported memory of pain. Parents reported their use of memory-reframing strategies and intervention feasibility and acceptability. The intervention did not result in significant differences in children's recalled or future pain. Parents rated the intervention as acceptable and feasible.

The effects of gastrointestinal symptoms on structural grey matter volume in youth.

Previous neuroimaging studies have examined the association between changes in brain structure and gastrointestinal symptoms (GIS), seen in disorders such as Irritable Bowel Syndrome and Irritable Bowel Disease. Studies in adults have found changes in white and grey matter volume (GMV) in patients with various gastrointestinal disorders. However, it is unclear whether GIS-related structural changes in the brain are limited to adults or could be present throughout the lifespan. Given that gastrointestinal disorders are typically diagnosed between 4 and 18 years old, we investigated GIS-induced morphological changes in pre-adolescents (8-10), adolescents (12-16 years) and young adults (17-21 years). Using a voxel-based morphometry (VBM) analysis, we compared regional grey matter volume (GMV) between participants with GIS and controls, using structural brain images from the Philadelphia Neurodevelopmental Cohort (PNC) database. A total of 211 participants (107 participants with GISs and 104 control participants) who had undergone structural magnetic resonance imaging were analysed. VBM analysis was used to objectively analyse GMV across the whole brain and compare between participants with GIS and controls. Participants experiencing GIS showed smaller GMV in regions within the limbic system/basal ganglia (bilateral caudate, bilateral ventral hippocampus, bilateral amygdala and bilateral superior orbital frontal cortex), and larger GMV in regions within the pain-matrix (thalamus, bilateral putamen, right mid-frontal gyrus) compared to controls. These differences were most prominent in the adolescent and young adult groups compared to pre-adolescents. In conclusion, the structural differences found in participants with GIS support the need for further research into the neurophysiological impact of these symptoms.