摘要
We hypothesize that susceptibility to post-traumatic stress disorder(PTSD) may be determined in part by aberrant microtubule-associated protein tau expression in neurons of critical brain structures. The following lines of evidence support this hypothesis. First, epidemiologic data suggest the involvement of genetic factors in the susceptibility to PTSD. Second, the common features of both abnormal tau expression and PTSD include amygdalar and hippocampal atrophy, upregulation of norepinephrine biosynthetic capacity inthe surviving locus coeruleus neurons and dysfunction of N-methyl-D-aspartate-receptors. Finally, our experiments using r Tg4510 mice, a model that over-expresses human mutant tau and develops age-dependent tauopathy, demonstrate that these animals display circling behavior thought to be related to states of anxiety. To detect the potential molecular mechanisms underlying PTSD episodes, laser-assisted/capture microdissection can be used with microarray analysis as an alternative approach to identify changes in gene expression in excitatory and/or inhibitory neurons in critical brain structures(i.e., hippocampus and amygdala) in response to the onset of PTSD.
We hypothesize that susceptibility to post-traumatic stress disorder(PTSD) may be determined in part by aberrant microtubule-associated protein tau expression in neurons of critical brain structures. The following lines of evidence support this hypothesis. First, epidemiologic data suggest the involvement of genetic factors in the susceptibility to PTSD. Second, the common features of both abnormal tau expression and PTSD include amygdalar and hippocampal atrophy, upregulation of norepinephrine biosynthetic capacity inthe surviving locus coeruleus neurons and dysfunction of N-methyl-D-aspartate-receptors. Finally, our experiments using r Tg4510 mice, a model that over-expresses human mutant tau and develops age-dependent tauopathy, demonstrate that these animals display circling behavior thought to be related to states of anxiety. To detect the potential molecular mechanisms underlying PTSD episodes, laser-assisted/capture microdissection can be used with microarray analysis as an alternative approach to identify changes in gene expression in excitatory and/or inhibitory neurons in critical brain structures(i.e., hippocampus and amygdala) in response to the onset of PTSD.
基金
Supported by In part by the Mayo Foundation,Mayo Clinic Jacksonville,Florida
National Center for Toxicological Research/FDA(Protocol P00710)to He Z
supported by a UAMS Hornick Award to Cui L
