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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 neocortical gene expression in the barrel field of somatosensory cortex. One hundred micrometers sagittal sections of brain hemispheres after in situ RNA hybridization with probes against COUP-TFI, Id2, RZRβ, and Cad8. Ages examined for each gene: P6, P10, P20, and P40. Oriented with dorsal up and rostral to the left. COUP-TFI exhibits robust expression the barrels at P6, and at later ages expression is mostly restricted to barrel septa (outlines of barrels, arrows in B1, D1). Id2 expression in the layer 4 barrel field is absent at P6 (arrow in A2), but some light expression in septa can be seen at P20 (arrows in C2). RZRβ exhibits robust expression in the barrel septa and hollows at P6 (arrow in A3), and although expression continues in both septa and hollows at later ages, the septal expression become relatively stronger (arrows in B3, D3). Cad8 displays limited expression in the barrel hollows but strong expression is seen in the septa at P6 and P10 (arrow in A4). Specific barrel expression is lost at P20 and P40 (C4, D4). Scale bar = 100 μm. Adapted from Dye et al. (2011b).
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Figure 7: Analysis of neocortical gene expression in the barrel field of somatosensory cortex. One hundred micrometers sagittal sections of brain hemispheres after in situ RNA hybridization with probes against COUP-TFI, Id2, RZRβ, and Cad8. Ages examined for each gene: P6, P10, P20, and P40. Oriented with dorsal up and rostral to the left. COUP-TFI exhibits robust expression the barrels at P6, and at later ages expression is mostly restricted to barrel septa (outlines of barrels, arrows in B1, D1). Id2 expression in the layer 4 barrel field is absent at P6 (arrow in A2), but some light expression in septa can be seen at P20 (arrows in C2). RZRβ exhibits robust expression in the barrel septa and hollows at P6 (arrow in A3), and although expression continues in both septa and hollows at later ages, the septal expression become relatively stronger (arrows in B3, D3). Cad8 displays limited expression in the barrel hollows but strong expression is seen in the septa at P6 and P10 (arrow in A4). Specific barrel expression is lost at P20 and P40 (C4, D4). Scale bar = 100 μm. Adapted from Dye et al. (2011b).

Mentions: The earliest sensory INCs documented in mice were found in the caudal cortex, in a location corresponding to developing visual cortex on embryonic (E) day 13.5 (Dye et al., 2011a, Figure 4). This growth of projections was correlated with Lhx2 expression and flanked by expression of Id2 and COUP-TF1 (Figure 4, top and Figure 5, top row). The areal patterning period (APP), or the time in which features of neocortical sensory and motor areas are established, was described and defined as the period from embryonic day (E) 16.5 to post-natal day (P) 3 in mice (Dye et al., 2011a, Figure 4). This APP occurs before eye opening and active whisking and represents a period of time where the distribution of INCs matures into an adult-like pattern, present as early as P3, where the borders of cortical sensory and motor areas are distinct and similar to what is observed in adults (Figure 4). Interestingly, although INC patterns remain fairly stable from P3 to P50 (early adulthood, Figure 4), gene expression patterns do not (Figures 5 and 6). Specifically, most expression patterns of the seven genes tested (see above list) in Dye et al. (2011a,b) either lose the location specificity of expression as the mouse ages, or decreases significantly over time (Figure 6). For example, Lhx2 expression correlated with developing visual and auditory cortical areas from E13.5-P20, after which expression becomes undetectable in cortical tissue (Figures 5 and 6).Of the seven genes we tested, four were expressed into adulthood but showed decreased levels of expression (COUP-TFI, Id2, Cad8, and RZRβ) across the cortex. Also, the expression of these four genes in the barrel field differed dramatically from the onset of barrel field formation to the adult barrel pattern (Figure 7). For example at P40, COUP-TF1 expression is dense in the barrel septa, where it was not present at P6 (Figure 7). This directed our hypothesis that genes expressed in cortex during adulthood may have switched their functional role from developmental to maintenance of cortical area borders or features.


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

Huffman K - Front Genet (2012)

Analysis of neocortical gene expression in the barrel field of somatosensory cortex. One hundred micrometers sagittal sections of brain hemispheres after in situ RNA hybridization with probes against COUP-TFI, Id2, RZRβ, and Cad8. Ages examined for each gene: P6, P10, P20, and P40. Oriented with dorsal up and rostral to the left. COUP-TFI exhibits robust expression the barrels at P6, and at later ages expression is mostly restricted to barrel septa (outlines of barrels, arrows in B1, D1). Id2 expression in the layer 4 barrel field is absent at P6 (arrow in A2), but some light expression in septa can be seen at P20 (arrows in C2). RZRβ exhibits robust expression in the barrel septa and hollows at P6 (arrow in A3), and although expression continues in both septa and hollows at later ages, the septal expression become relatively stronger (arrows in B3, D3). Cad8 displays limited expression in the barrel hollows but strong expression is seen in the septa at P6 and P10 (arrow in A4). Specific barrel expression is lost at P20 and P40 (C4, D4). Scale bar = 100 μm. Adapted from Dye et al. (2011b).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 7: Analysis of neocortical gene expression in the barrel field of somatosensory cortex. One hundred micrometers sagittal sections of brain hemispheres after in situ RNA hybridization with probes against COUP-TFI, Id2, RZRβ, and Cad8. Ages examined for each gene: P6, P10, P20, and P40. Oriented with dorsal up and rostral to the left. COUP-TFI exhibits robust expression the barrels at P6, and at later ages expression is mostly restricted to barrel septa (outlines of barrels, arrows in B1, D1). Id2 expression in the layer 4 barrel field is absent at P6 (arrow in A2), but some light expression in septa can be seen at P20 (arrows in C2). RZRβ exhibits robust expression in the barrel septa and hollows at P6 (arrow in A3), and although expression continues in both septa and hollows at later ages, the septal expression become relatively stronger (arrows in B3, D3). Cad8 displays limited expression in the barrel hollows but strong expression is seen in the septa at P6 and P10 (arrow in A4). Specific barrel expression is lost at P20 and P40 (C4, D4). Scale bar = 100 μm. Adapted from Dye et al. (2011b).
Mentions: The earliest sensory INCs documented in mice were found in the caudal cortex, in a location corresponding to developing visual cortex on embryonic (E) day 13.5 (Dye et al., 2011a, Figure 4). This growth of projections was correlated with Lhx2 expression and flanked by expression of Id2 and COUP-TF1 (Figure 4, top and Figure 5, top row). The areal patterning period (APP), or the time in which features of neocortical sensory and motor areas are established, was described and defined as the period from embryonic day (E) 16.5 to post-natal day (P) 3 in mice (Dye et al., 2011a, Figure 4). This APP occurs before eye opening and active whisking and represents a period of time where the distribution of INCs matures into an adult-like pattern, present as early as P3, where the borders of cortical sensory and motor areas are distinct and similar to what is observed in adults (Figure 4). Interestingly, although INC patterns remain fairly stable from P3 to P50 (early adulthood, Figure 4), gene expression patterns do not (Figures 5 and 6). Specifically, most expression patterns of the seven genes tested (see above list) in Dye et al. (2011a,b) either lose the location specificity of expression as the mouse ages, or decreases significantly over time (Figure 6). For example, Lhx2 expression correlated with developing visual and auditory cortical areas from E13.5-P20, after which expression becomes undetectable in cortical tissue (Figures 5 and 6).Of the seven genes we tested, four were expressed into adulthood but showed decreased levels of expression (COUP-TFI, Id2, Cad8, and RZRβ) across the cortex. Also, the expression of these four genes in the barrel field differed dramatically from the onset of barrel field formation to the adult barrel pattern (Figure 7). For example at P40, COUP-TF1 expression is dense in the barrel septa, where it was not present at P6 (Figure 7). This directed our hypothesis that genes expressed in cortex during adulthood may have switched their functional role from developmental to maintenance of cortical area borders or features.

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