January 10th, 2018
Genetic Expression Defects Associated with Neurobehavioral Disorders in Rats – conclusion
Delineating the genetic links between genes and behavior may help delineate the etiology of some neurobehavioral disorders such as dyslexia. This paper reviews such a genetic link to dyslexia with subsequent examination of associated behavior in experimental models.
From the review, neurobehavioral disorders observed in animal models may be associated with impaired neuronal migration. Such impairment in migration results from curtailed expressions of genes such as DYX1C, KIAA0319 and DCDC2, which have been identified as candidate genes for dyslexia. This is specifically buttressed by observations that replenishing such expression capabilities, leads to recovery of neuronal migration to almost equal that of cells that had not been targeted for the knockdown of candidate genes. Association of these genes may however not be absolute, since some of the suggested putative alleles have not replicated such association in other populations.
However, whenever genetic mutations result into impaired migration, malformations that correlate with those found in postmortem assays of dyslexics’ brains result. Such malformations include ectopias and mycrogyria in the cortex that are associated with behavioral deficits in auditory processing and working memory in rats treated for suppression of genes associated with susceptibility with dyslexia. Other malformations such as laminar disruptions are associated with curtailed working memory capabilities. Observations that young mice may be more affected as reflected in auditory processing tests than adult mice, also correlate with observations that impairment of neuronal migration following the knockdown of candidate genes is more pronounced in embryonic relative to adult forms. Therefore, genetic mutations could explain some of the neurobehavioral disorders noted in experimental models and, subsequently, such links better the understanding of neurobehavioral disorders affecting individuals.
Gabel, Lisa A., et al. “Progress Towards a Cellular Neurobiology of Reading Disability.” Neurobiology of Disease 38.2 (2010): 173-180. ScienceDirect. Web. 15 March 2011.
Galaburda, Albert M., et al. “From Genes to Behavior in Developmental Dyslexia.” Nature Neuroscience 9.10 (2006): 1213-1217. Web. 15 March 2011.
Meng, Haiying, et al. “DCDC2 is Associated with Reading Disability and Modulates Neuronal Development in the Brain.” PNAS 102.47 (2005): 17053-17058. Web. 15 March 2011.
Paracchini, Silvia, et al. “The Chromosome 6p22 Haplotype Associated with Dyslexia Reduces the Expression of KIAA0319, a Novel Gene Involved in Neuronal Migration.” Human Molecular Genetics 15.10 (2006): 1659-1666. Web. 15 March 2011.
Peiffer, Ann M., et al. “Impaired Detection of Variable Duration Embedded Tones in Ectopic NZB/BINJ Mice.” NeuroReport 12.13 (2001): 2875-2879. Web. 15 March 2011.
Rosen, Glenn D., et al. “Disruption of Neuronal Migration by RNAi of DYX1C1 Results in Neocortical and Hippocampal Malformations.” Cerebral Cortex 17.11 (2007): 2562-2572. Web. 15 March 2011.
Szalkowski, C. E., et al. “Persistent Spatial Working Memory Deficits in Rats Following in utero RNAi of Dyx1c1.” Genes, Brain and Behavior 10.2 (2011): 244-252. Web. 15 March 2011.
Threlkeld, Steven W., et al. “Developmental Disruptions and Behavioral Impairments in Rats Following in utero RNAi of Dyx1c1.” Brain Research Bulletin 71.5 (2007): 508-514. ScienceDirect. Web. 15 March 2011.
Wang, Y., et al. “DYX1C1 Functions in Neuronal Migration in Developing Neocortex.” Neuroscience 143.2 (2006): 515-522. Web. 15 March 2011.