Abstract
A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.
Highlights
A substantial number of genes in the brain undergo developmental changes in psychiatrically normal subjects [1,2,3]
A normal mitochondrial function is critical for synaptogenesis and spine formation [58,59], and for normal apoptosis to occur [60,61]
Increased expression of the genes associated with mitochondrial function in the prefrontal cortex (PFC) during development may reflect ongoing maturation and neuronal plasticity, especially during adolescence [36]
Summary
A substantial number of genes in the brain undergo developmental changes in psychiatrically normal subjects [1,2,3]. It is likely that disruption of normal expression pattern of the susceptibility genes during development may contribute to the development of psychiatric symptoms in adulthood. Animal studies have shown that adolescence is a sensitive period for the development of stress and anxiety responses in adulthood [4,5]. Repeated exposure of rats to a stressor across an adolescent period increase fearfulness in a novel environment in adulthood and resulted in lower levels of dopamine receptor subtype-2 levels in the prefrontal cortex (PFC) [6]. A slow maturation of the PFC toward adulthood may contribute to different stress responses in animals [9]. These studies implicate a functional relationship between brain development, stress and altered fear behavior
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
