Project description:Brain and spinal injury often impair sensorimotor processing in the spinal cord and reduce mobility. We established that complete transection of corticospinal pathways in the pyramids leads to increased spasms, excessive mono- and polysynaptic spinal reflexes and impaired locomotion in rats. Intramuscular neurotrophin-3 treatment at a clinically-feasible time-point after injury reduced these signs of spasticity. We found Neurotrophin-3 reduced spastic movements and improved neurophysiological sensorimotor control. Furthermore, the balance of inhibitory and excitatory synapses in the cord and the level of an ion transporter in motor neuron membranes required for normal reflexes were normalized. We discovered that Neurotrophin-3 is transported in sensory afferents from muscles to the dorsal root ganglia. Using genome-wide small RNA sequencing of the whole cervical level 6-8 dorsal root ganglia, we explored miRNA changes in afferent neurons that were present 10 weeks after bilateral pyramidotomy. Many of the dysregulated genes are involved in axon guidance and plasticity. Intramuscular neurotrophin-3 treatment normalized many of those gene changes and may be one of the mechanisms how reflexes, functional recovery and molecular markers in the spinal cord are restored. This identifies neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.
Project description:Brain and spinal injury often impair sensorimotor processing in the spinal cord and reduce mobility. Cortical stroke in rats leads to long-term deficits in dexterity and walking. Subcutaneous neurotrophin-3 infusion initiated at a clinically-feasible time-point after injury improved walking and dexterity. We discovered that Neurotrophin-3 is transported in sensory afferents from muscles to the dorsal root ganglia. Using genome-wide RNA sequencing of the whole cervical level 6-8 dorsal root ganglia, we sought gene changes in afferent neurons that were present at two timepoints after stroke.
Project description:Brain and spinal injury often impair sensorimotor processing in the spinal cord and reduce mobility. We established that complete transection of corticospinal pathways in the pyramids leads to increased spasms, excessive mono- and polysynaptic spinal reflexes and impaired locomotion in rats. Intramuscular neurotrophin-3 treatment at a clinically-feasible time-point after injury reduced these signs of spasticity. We found Neurotrophin-3 reduced spastic movements and improved neurophysiological sensorimotor control. Furthermore, the balance of inhibitory and excitatory synapses in the cord and the level of an ion transporter in motor neuron membranes required for normal reflexes were normalized. We discovered that Neurotrophin-3 is transported in sensory afferents from muscles to the dorsal root ganglia. Using genome-wide RNA sequencing of the whole cervical level 6-8 dorsal root ganglia, we explored mRNA changes in afferent neurons that were present 10 weeks after bilateral pyramidotomy. Many of the dysregulated genes are involved in axon guidance and plasticity. Intramuscular neurotrophin-3 treatment normalized many of those gene changes and may be one of the mechanisms how reflexes, functional recovery and molecular markers in the spinal cord are restored. This identifies neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.
Project description:We report 33 microRNAs are differentially expressed in the dorsal raphe and/or amygdala of rats selectively bred for high and low locomotor response to novelty (high responder and low responder rats)
Project description:Genome-wide analyses reveal DNA methylation in the central nucleus of the amygdala is linked to anxious temperament in young primates
Project description:We identified 271 transcripts as differentially regulated in the dorsal raphe and/or the amygdala of high-responder and low-responder rats
Project description:The amygdala or amygdala-like structure in the brain are found in all vertebrates, and plays a critical role for emotional processing. But the cellular architecture of amygdala and how they evolved are still elusive. Here, we generated single-nucleus RNA-sequencing data for more than 200,000 cells in human, macaque, mouse and chicken amygdala. Abundant neuronal cell types derived from different subnuclei of amygdala were identified in all datasets. Cross-species analyses revealed GABAergic neurons and GABAergic neuron-enriched subnuclei of amygdala were well-conserved in cellular composition and marker gene expression, whereas glutamatergic neuron-enriched subnuclei were relatively divergent. Furthermore, we discovered that LAMP5+ interneurons were much more numerous in primates, while DRD2+ GABAergic neurons, LAMP5+ and SATB2+ glutamatergic neurons were predominant in the human central amygdalar nucleus (CEA) and basolateral amygdala complex (BLA), respectively. In addition, we also identified GABAergic neuron-enriched subnuclei of amygdala in the chicken. Altogether, our study highlight extremely cell-type diversity in the amygdala across species and their species-specifc adaptations.
Project description:Axonal regeneration is enhanced by prior conditioning peripheral nerve lesions. Here we show that Xenopus dorsal root ganglia (DRGs) with attached peripheral nerves (PN-DRGs) can be conditioned in vitro, thereafter showing enhanced axonal growth in response to neurotrophins, similar to preparations conditioned by axotomy in vivo. In contrast to freshly dissected preparations, conditioned PN-DRGs show abundant neurotrophin-induced axonal growth in the presence of actinomycin D, suggesting synthesis of mRNA encoding proteins necessary for axonal elongation occurs during the conditioning period, and this was confirmed by oligonucleotide micro-array analysis.
Project description:Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications for the design of gene expression studies as well as for the potential effects of xenobiotics on these regions that regulate autonomic and emotional states. Micropunches of dorsal vagal complex (DVC) and central nucleus of the amygdala (CeA) were collected from male, Sprague Dawley rats at three different times of the day. Animals were not experimentally different in any way except for the time of sacrifice and collction. Gene expression of 145 genes were measured with Fluidigm's Biomark 96.96 platform.
Project description:The experiment is part of a study aimed at identifying and studying genes that contribute to differences in oestrous behaviour expression and fertility levels of dairy cows. Samples from 4 brain areas (dorsal hypothalamus, ventral hypothalamus, amygdala and hippocampus) and the anterior pituitary were collected from 28 primiparous Holstein Friesian cows, 14 of which were sacrificed at start of oestrus and 14 at mid of oestrous cycle. Differential gene expression between the 2 phases of oestrous cycle as well as the association of gene expression patterns with the level of oestrous behaviour expression are studied.