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The developing, aging neocortex: how genetics and epigenetics influence early developmental patterning and age-related change.

Huffman K - Front Genet (2012)

Bottom Line: During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input.We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging.We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging on the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of California Riverside, CA, USA.

ABSTRACT
A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory, and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging on the brain.

No MeSH data available.


Related in: MedlinePlus

Analysis of COUP-TFI gene expression in P10 and P72 control mice and mice bilaterally enucleated at birth. One hundred micrometers coronal sections of P10 and P72 brain hemispheres following in situ hybridization with a probe against COUP-TFI. At P10 strong COUP-TFI expression is seen in layer 4 of the caudo/lateral cortex in both control and enucleated animals. Layer 4 COUP-TFI expression at P72 is maintained in the enucleated animal, but is notably reduced in control animals (black arrows).Additionally, expression of COUP-TFI, although present in a smaller domain due to the decreased sized of the nucleus after enucleation, shows increased expression in the LGN of mice enucleated at birth as compared to controls at P72 (white arrows). Normal developmental time limits of COUP-TFI expression in mouse brain are extended by removal of visual activity, perhaps representing an extension of the critical for plasticity. Oriented dorsal up and lateral to the right. (Data from a published abstract, Society for Neuroscience conference, Huffman et al., 2010).
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Figure 8: Analysis of COUP-TFI gene expression in P10 and P72 control mice and mice bilaterally enucleated at birth. One hundred micrometers coronal sections of P10 and P72 brain hemispheres following in situ hybridization with a probe against COUP-TFI. At P10 strong COUP-TFI expression is seen in layer 4 of the caudo/lateral cortex in both control and enucleated animals. Layer 4 COUP-TFI expression at P72 is maintained in the enucleated animal, but is notably reduced in control animals (black arrows).Additionally, expression of COUP-TFI, although present in a smaller domain due to the decreased sized of the nucleus after enucleation, shows increased expression in the LGN of mice enucleated at birth as compared to controls at P72 (white arrows). Normal developmental time limits of COUP-TFI expression in mouse brain are extended by removal of visual activity, perhaps representing an extension of the critical for plasticity. Oriented dorsal up and lateral to the right. (Data from a published abstract, Society for Neuroscience conference, Huffman et al., 2010).

Mentions: Our study of gene expression and INCs in the Fgf8 mutant and the normal wild-type mouse spanning from embryogenesis to adulthood led to the idea that gene expression not only regulates INC position but that the decline of cortical gene expression throughout life correlated with period closures of sensory critical periods. If, indeed, gene expression regulates critical period closure, we posit that sensory deprivation, which is known to extend the critical period for plasticity in cortex, would also extend the decline of gene expression. In a P72 mouse bilaterally enucleated at birth, we observed increased expression of COUP-TFI present in the caudal neocortex when compared to levels of expression in control mice (Huffman et al., 2010; Figure 8). This extension of normal gene expression in a mouse with long term visual deprivation supports our hypothesis that natural reduction of gene expression in cortex with age plays a role in closure of critical periods for plasticity and that sensory deprivation may extend critical periods via extension of cortical gene expression.


The developing, aging neocortex: how genetics and epigenetics influence early developmental patterning and age-related change.

Huffman K - Front Genet (2012)

Analysis of COUP-TFI gene expression in P10 and P72 control mice and mice bilaterally enucleated at birth. One hundred micrometers coronal sections of P10 and P72 brain hemispheres following in situ hybridization with a probe against COUP-TFI. At P10 strong COUP-TFI expression is seen in layer 4 of the caudo/lateral cortex in both control and enucleated animals. Layer 4 COUP-TFI expression at P72 is maintained in the enucleated animal, but is notably reduced in control animals (black arrows).Additionally, expression of COUP-TFI, although present in a smaller domain due to the decreased sized of the nucleus after enucleation, shows increased expression in the LGN of mice enucleated at birth as compared to controls at P72 (white arrows). Normal developmental time limits of COUP-TFI expression in mouse brain are extended by removal of visual activity, perhaps representing an extension of the critical for plasticity. Oriented dorsal up and lateral to the right. (Data from a published abstract, Society for Neuroscience conference, Huffman et al., 2010).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3473232&req=5

Figure 8: Analysis of COUP-TFI gene expression in P10 and P72 control mice and mice bilaterally enucleated at birth. One hundred micrometers coronal sections of P10 and P72 brain hemispheres following in situ hybridization with a probe against COUP-TFI. At P10 strong COUP-TFI expression is seen in layer 4 of the caudo/lateral cortex in both control and enucleated animals. Layer 4 COUP-TFI expression at P72 is maintained in the enucleated animal, but is notably reduced in control animals (black arrows).Additionally, expression of COUP-TFI, although present in a smaller domain due to the decreased sized of the nucleus after enucleation, shows increased expression in the LGN of mice enucleated at birth as compared to controls at P72 (white arrows). Normal developmental time limits of COUP-TFI expression in mouse brain are extended by removal of visual activity, perhaps representing an extension of the critical for plasticity. Oriented dorsal up and lateral to the right. (Data from a published abstract, Society for Neuroscience conference, Huffman et al., 2010).
Mentions: Our study of gene expression and INCs in the Fgf8 mutant and the normal wild-type mouse spanning from embryogenesis to adulthood led to the idea that gene expression not only regulates INC position but that the decline of cortical gene expression throughout life correlated with period closures of sensory critical periods. If, indeed, gene expression regulates critical period closure, we posit that sensory deprivation, which is known to extend the critical period for plasticity in cortex, would also extend the decline of gene expression. In a P72 mouse bilaterally enucleated at birth, we observed increased expression of COUP-TFI present in the caudal neocortex when compared to levels of expression in control mice (Huffman et al., 2010; Figure 8). This extension of normal gene expression in a mouse with long term visual deprivation supports our hypothesis that natural reduction of gene expression in cortex with age plays a role in closure of critical periods for plasticity and that sensory deprivation may extend critical periods via extension of cortical gene expression.

Bottom Line: During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input.We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging.We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging on the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of California Riverside, CA, USA.

ABSTRACT
A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory, and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging on the brain.

No MeSH data available.


Related in: MedlinePlus