Project description:Neuropsychiatric consequences of poorly controlled seizures that begin in childhood can be devastating. School failure or behavioral difficulty in a child with epilepsy is common and can become the focus of concern for families. Current antiepileptic drugs compound problems with their CNS side effects; effective therapy is currently limited as little is known about the cellular and molecular changes caused by seizures in the developing brain. This study will investigate transcriptional regulation induced by early-life seizures and explore alternative nonpharmacological therapeutic strategies in reversing damages of early-life seizures. We will study the therapeutic efficacy of environmental enrichment in reducing seizure-induced neuronal injury and in modifying gene expression alterations. We will explore molecular mechanisms underlying the beneficial effects of enriched environment and examine how different genes act in concert to influence the outcome of seizure-induced damage. To test the effect of environmental enrichment in modifying KA seizure-induced alterations in gene expression. We hypothesize that environmental enrichment enhances plastic, homeostatic response of immature brain to excessive, dysregulating seizure activity and protect against maladaptive response of developing animals to seizures. After inducing seizures by systemic injection of KA (8 mg/kg) or PBS injections (control) at P20, we will randomly assign P21 male Long Evans rats to 4 groups: enrichment housing (control-enriched; SE-enriched) or to standard vivarium cages (control; SE). Sixteen animals (8 control-enriched; 8 SE-enriched) will be housed as a group in a plastic rectangular cage measuring 115cm x 80 cm containing a running wheel, tunnels, rubber balls, a maze, a mirror, and a clock with a cyclist pendulum. Control and KA will be housed individually in a standard cage. Four litters will be used for each run of experiment and the experiment will be repeated once to obtain 16 animals per group. At P30, 240 h after KA or PBS, animals will be deeply anesthetized with isoflurane, decapitated for total RNA preparation (half brain for each, n = 12 per group). Total RNA will be isolated from each hippocampus individually, and equal amounts of RNA from 4 hippocampi will be pooled for each Genechip. Three independent hybridizations will be performed per condition (total of 12 Genechip Rat Expression Set 230).
Project description:Neuropsychiatric consequences of poorly controlled seizures that begin in childhood can be devastating. School failure or behavioral difficulty in a child with epilepsy is common and can become the focus of concern for families. Current antiepileptic drugs compound problems with their CNS side effects; effective therapy is currently limited as little is known about the cellular and molecular changes caused by seizures in the developing brain. This study will investigate transcriptional regulation induced by early-life seizures and explore alternative nonpharmacological therapeutic strategies in reversing damages of early-life seizures. We will study the therapeutic efficacy of environmental enrichment in reducing seizure-induced neuronal injury and in modifying gene expression alterations. We will explore molecular mechanisms underlying the beneficial effects of enriched environment and examine how different genes act in concert to influence the outcome of seizure-induced damage. To test the effect of environmental enrichment in modifying KA seizure-induced alterations in gene expression. We hypothesize that environmental enrichment enhances plastic, homeostatic response of immature brain to excessive, dysregulating seizure activity and protect against maladaptive response of developing animals to seizures. After inducing seizures by systemic injection of KA (8 mg/kg) or PBS injections (control) at P20, we will randomly assign P21 male Long Evans rats to 4 groups: enrichment housing (control-enriched; SE-enriched) or to standard vivarium cages (control; SE). Sixteen animals (8 control-enriched; 8 SE-enriched) will be housed as a group in a plastic rectangular cage measuring 115cm x 80 cm containing a running wheel, tunnels, rubber balls, a maze, a mirror, and a clock with a cyclist pendulum. Control and KA will be housed individually in a standard cage. Four litters will be used for each run of experiment and the experiment will be repeated once to obtain 16 animals per group. At P30, 240 h after KA or PBS, animals will be deeply anesthetized with isoflurane, decapitated for total RNA preparation (half brain for each, n = 12 per group). Total RNA will be isolated from each hippocampus individually, and equal amounts of RNA from 4 hippocampi will be pooled for each Genechip. Three independent hybridizations will be performed per condition (total of 12 Genechip Rat Expression Set 230). Keywords: dose response
Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9.