Dietary intake alters behavioral recovery and gene expression profiles in the brain of juvenile rats that have experienced a concussion

Concussion and mild traumatic brain injury (mTBI) research has made minimal progress diagnosing who will suffer from lingering symptomology or generating effective treatment strategies. Research demonstrates that dietary intake affects many biological systems including brain and neurological health. This study determined if exposure to a high fat diet (HFD) or caloric restriction (CR) altered post-concussion susceptibility or resiliency using a rodent model of pediatric concussion. Rats were maintained on HFD, CR, or standard diet (STD) throughout life (including the prenatal period and weaning). At postnatal day 30, male and female rats experienced a concussion or a sham injury which was followed by 17 days of testing. Prefrontal cortex and hippocampus tissue was collected for molecular profiling. Gene expression changes in BDNF, CREB, DNMT1, FGF-2, IGF1, LEP, PGC-1α, SIRT1, Tau, and TERT were analyzed with respect to injury and diet. Analysis of telomere length (TL) using peripheral skin cells and brain tissue found that TL in skin significantly correlated with TL in brain tissue and TL was affected by dietary intake and injury status. With respect to mTBI outcomes, diet was correlated with recovery as animals on the HFD often displayed poorer performance than animals on the CR diet. Molecular analysis demonstrated that diet induced epigenetic changes that can be associated with differences in individual predisposition and resiliency to post-concussion syndrome

Neuroendocrine Whiplash: Slamming the Breaks on Anabolic-Androgenic Steroids Following Repetitive Mild Traumatic Brain Injury in Rats May Worsen Outcomes

Sport-related concussion is an increasingly common injury among adolescents, with repetitive mild traumatic brain injuries (RmTBI) being a significant risk factor for long-term neurobiological and psychological consequences. It is not uncommon for younger professional athletes to consume anabolic-androgenic steroids (AAS) in an attempt to enhance their performance, subjecting their hormonally sensitive brains to potential impairment during neurodevelopment. Furthermore, RmTBI produces acute neuroendocrine dysfunction, specifically in the anterior pituitary, disrupting the hypothalamic-pituitary adrenal axis, lowering cortisol secretion that is needed to appropriately respond to injury. Some AAS users exhibit worse symptoms post-RmTBI if they quit their steroid regime. We sought to examine the pathophysiological outcomes associated with the abrupt cessation of the commonly abused AAS, Metandienone (Met) on RmTBI outcomes in rats. Prior to injury, adolescent male rats received either Met or placebo, and exercise. Rats were then administered RmTBIs or sham injuries, followed by steroid and exercise cessation (SEC) or continued treatment. A behavioral battery was conducted to measure outcomes consistent with clinical representations of post-concussion syndrome and chronic AAS exposure, followed by analysis of serum hormone levels, and qRT-PCR for mRNA expression and telomere length. RmTBI increased loss of consciousness and anxiety-like behavior, while also impairing balance and short-term working memory. SEC induced hyperactivity while Met treatment alone increased depressive-like behavior. There were cumulative effects whereby RmTBI and SEC exacerbated anxiety and short-term memory outcomes. mRNA expression in the prefrontal cortex, amygdala, hippocampus, and pituitary were modified in response to Met and SEC. Analysis of telomere length revealed the negative impact of SEC while Met and SEC produced changes in serum levels of testosterone and corticosterone. We identified robust changes in mRNA to serotonergic circuitry, neuroinflammation, and an enhanced stress response. Interestingly, Met treatment promoted glucocorticoid secretion after injury, suggesting that maintained AAS may be more beneficial than abstaining after mTBI

THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity

Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience‐dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9‐Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience‐dependent structural plasticity we gave Long‐Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi‐Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug.Both repeated exposure to Delta 9‐THC and housing in complex environments changes the morphology of dendrites in mPFC, OFC, and NAcc. Prior exposure to THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141383/1/syn22020.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141383/2/syn22020_am.pd

Intensity matters : effects of prenatal stress on the developing brain / Richelle Mychasiuk

xx, 201 leaves ; 29 cmThis thesis examines the behavioral, structural, cellular, and epigenetic changes observed in offspring exposed to different prenatal stressors. A number of questions were answered in this thesis that contribute to a basic understanding of the mechanisms by which early experiences alter long-term outcomes. These include: 1) What epigenetic modifications are associated with prenatal stress? 2) What are the structural and cellular changes in the brains of offspring that correspond to prenatal stress exposure? 3) How do these epigenetic and structural changes manifest as behavioral changes? And 4) What are the consequences of varying the level of prenatal stress?The key findings were that not all prenatal stress is the same. Variations to the intensity and nature of the stress dramatically alter offspring outcomes. Second, prenatal stress produces changes at many levels and these changes can be functionally related. Expression changes were identified in genes involved in altering dendritic morphology, which in turn modifies behaviour. For the first time, a comprehensive examination of brain plasticity occurred following prenatal stress. Additionally, this thesis demonstrated that brain changes related to prenatal stress are age-dependent and sex-dependent. The effects of prenatal stress on the pre-weaning brain are dramatically different than those observed in adulthood. Also, the sex of the offspring significantly influences neuroanatomical and epigenetic modifications. This finding is of critical importance because a majority of prenatal stress research is conducted on male offspring only. Taken together these discoveries emphasize that perturbations to development during the prenatal period produce persistent changes in the structure and functioning of the brain that will influence all subsequent experience

Liver irradiation causes distal bystander effects in the rat brain and affects animal behavior

Sherpa Romeo blue journal. Open access: Creative Commons Attribution 3.0 License (CC BY 3.0) applies.Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neurocognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of fH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.Ye

Profound and sexually dimorphic effects of clinically-relevant low dose scatter irradiation on the brain and behavior

Sherpa Romeo green journal: open accessIrradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way.Ye

Necessary but not sufficient? Engaging young people in the development of an avatar-based online intervention designed to provide psychosocial support to young people affected by their own or a family member's cancer diagnosis

Objective: This paper discusses the challenges and successes of engaging young people in a project aimed at developing an online counselling intervention for young people affected by cancer. Context: For younger people with a diagnosis of cancer or who are caring for someone with cancer the psychosocial consequences can create significant challenges for their social and educational development. Whilst young people have been shown to be reluctant to make use of traditional face-to-face counselling, research is beginning to suggest that effective therapeutic relationships can be formed with young people online. Design: The first phase of the study involved working with a “Young Persons Panel” of healthy school pupils and university students to develop and pilot an online counselling intervention and study materials in preparation for a pilot evaluation of the intervention. Intervention: An avatar-based virtual reality counselling world was created where young people can create their own avatar and receive counselling over the internet from a qualified counsellor via an avatar in a virtual reality world. Findings: The process of engaging young people in the C:EVOLVE project enabled a unique intervention to be developed and demonstrated positive developmental opportunities. However, despite the rigorous approach to the development of the intervention, initial attempts within the pilot evaluation phase of the study showed difficulties recruiting to the study and this phase of the study has currently ceased whilst further exploratory work takes place Conclusion: This study has demonstrated the complexities of intervention development and evaluation research targeted at young people and the challenges created when attempting to bring clinical practice and research evaluation together. Keywords: online counselling, cancer, young people, intervention development, avatar counselling

The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning

The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, relatively little information is available about the impact of environmental enrichment on offspring behaviour if enrichment is implemented only during this period. Here, environmental enrichment was provided from postnatal day 1 until weaning. On post-natal day 9, maternal behaviour and nonmaternal behaviour of the dam was observed. Nursing time in the enriched group was reduced but dams showed more non-maternal appetitive behaviours. Offspring were exposed to either the open field or the elevated plus maze (EPM) after weaning. In the open field, rats from the enriched group approached the more aversive inner zone of the open field later than control rats. Offspring from the enriched group made fewer entries into the inner zone and spent less time in this part of the arena. Enrichment had no impact on behaviour in the EPM. The present study provides evidence that postnatal enrichment can interfere with maternal behaviour in rats and can possibly lead to increased anxiety in the offspring. The findings suggest that enrichment procedures can have potentially unintended effects, interfering with the development of emotional behaviours in rats

Pre-existing Toxoplasma gondii infection increases susceptibility to pentylenetetrazol-induced seizures independent of traumatic brain injury in mice

IntroductionPost-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI), and neuroinflammation is implicated in increased seizure susceptibility and epileptogenesis. However, how common clinical factors, such as infection, may modify neuroinflammation and PTE development has been understudied. The neurotropic parasite, Toxoplasma gondii (T. gondii) incurably infects one-third of the world’s population. Thus, many TBI patients have a pre-existing T. gondii infection at the time of injury. T. gondii infection results in chronic low-grade inflammation and altered signaling pathways within the brain, and preliminary clinical evidence suggest that it may be a risk factor for epilepsy. Despite this, no studies have considered how a pre-existing T. gondii infection may alter the development of PTE.MethodsThis study aimed to provide insight into this knowledge gap by assessing how a pre-existing T. gondii infection alters susceptibility to, and severity of, pentylenetetrazol (PTZ)-induced seizures (i.e., a surrogate marker of epileptogenesis/PTE) at a chronic stage of TBI recovery. We hypothesized that T. gondii will increase the likelihood and severity of seizures following PTZ administration, and that this would occur in the presence of intensified neuroinflammation. To test this, 6-week old male and female C57BL/6 Jax mice were intraperitoneally injected with 50,000 T. gondii tachyzoites or with the PBS vehicle only. At 12-weeks old, mice either received a severe TBI via controlled cortical impact or sham injury. At 18-weeks post-injury, mice were administered 40 mg/kg PTZ and video-recorded for evaluation of seizure susceptibility. Fresh cortical tissue was then collected for gene expression analyses.ResultsAlthough no synergistic effects were evident between infection and TBI, chronic T. gondii infection alone had robust effects on the PTZ-seizure response and gene expression of markers related to inflammatory, oxidative stress, and glutamatergic pathways. In addition to this, females were more susceptible to PTZ-induced seizures than males. While TBI did not impact PTZ responses, injury effects were evident at the molecular level.DiscussionOur data suggests that a pre-existing T. gondii infection is an important modifier of seizure susceptibility independent of brain injury, and considerable attention should be directed toward delineating the mechanisms underlying this pro-epileptogenic factor

Aboriginal Children and Their Caregivers Living with Low Income: Outcomes from a Two-Generation Preschool Program

The development of preschool children of Aboriginal heritage is jeopardized by the inter-generational transmission of risk that has created, and continues to create, social disadvantage. Early intervention programs are intended to mitigate the impact of social disadvantage. Yet, evidence of the effectiveness of these programs for children of Aboriginal heritage is limited. The purpose of this study was to examine the effects of a two-generation, multi-cultural preschool program on 45 children of Aboriginal heritage and their caregivers. We used a single-group, pretest (program intake)/posttest (program exit) design with follow-up when the children were 7 years old. We used an observational measure of child receptive language (Peabody Picture Vocabulary Test–III) and caregiver-reported measures of child development (Nipissing District Developmental Screen), risk for child maltreatment (Adult-Adolescent Parenting Inventory; AAPI), parenting stress (Parenting Stress Index; PSI), self-esteem (Rosenberg Self-Esteem scale; RSE), and life skills (Community Life Skills scale; CLS). Using paired t-tests we found statistically significant increases in child receptive language scores between intake and exit, and repeated-measures ANOVA showed that these improvements were maintained up to age 7 years. For caregivers, Pearson’s correlations demonstrated that risk for child maltreatment, parenting stress, self-esteem, and life skills were stable over time. Results of this study suggest that children of Aboriginal heritage can benefit from participation in a two-generation, multi-cultural preschool program. Their caregivers may have received greater benefit if issues of intergenerational transmission of the negative influences of residential schools were addressed as part of programming