Ontogenetic Alterations in Molecular and Structural Correlates of Dendritic Growth after Developmental Exposure to Polychlorinated Biphenyls

By Lein, Pamela J.; Yang, Dongren et al. | Environmental Health Perspectives, April 2007 | Go to article overview

Ontogenetic Alterations in Molecular and Structural Correlates of Dendritic Growth after Developmental Exposure to Polychlorinated Biphenyls


Lein, Pamela J., Yang, Dongren, Bachstetter, Adam D., Tilson, Hugh A., Harry, G. Jean, Mervis, Ronald F., Kodavanti, Prasada Rao S., Environmental Health Perspectives


OBJECTIVE: Perinatal exposure to polychlorinated biphenyls (PCBs) is associated with decreased IQ scores, impaired learning and memory, psychomotor difficulties, and attentional deficits in children. It is postulated that these neuropsychological deficits reflect altered patterns of neuronal connectivity. To test this hypothesis, we examined the effects of developmental PCB exposure on dendritic growth.

METHODS: Rat dams were gavaged from gestational day 6 through postnatal day (PND) 21 with vehicle (corn oil) or the commercial PCB mixture Aroclor 1254 (6 mg/kg/day). Dendritic growth and molecular markers were examined in pups during development.

RESULTS: Golgi analyses of CA1 hippocampal pyramidal neurons and cerebellar Purkinge cells indicated that developmental exposure to PCBs caused a pronounced age-related increase in dendritic growth. Thus, even though dendritic lengths were significantly attenuated in PCB-treated animals at PND22, the rate of growth was accelerated at later ages such that by PND60, dendritic growth was comparable to or even exceeded that observed in vehicle controls. Quantitative reverse transcriptase polymerase chain reaction analyses demonstrated that from PND4 through PND21, PCBs generally increased expression of both spinophilin and RC3/neurogranin mRNA in the hippocampus, cerebellum, and cortex with the most significant increases observed in the cortex.

CONCLUSIONS: This study demonstrates that developmental PCB exposure alters the ontogenetic profile of dendritogenesis in critical brain regions, supporting the hypothesis that disruption of neuronal connectivity contributes to neuropsychological deficits seen in exposed children.

KEY WORDS: dendritogenesis, developmental neurotoxicology, learning and memory, molecular markers, polychlorinated biphenyls. Environ Health Perspect 115:556-563 (2007). doi:10.1289/ehp.9773 available via http://dx.doi.org/ [Online 16 January 2007]

**********

The increasing prevalence of neurodevelopmental disorders, including intellectual retardation, autism, and attention deficit hyperreactivity disorder (ADHD) cannot be explained entirely by genetic mechanisms (Faraone and Khan 2006; Muhle et al. 2004; Palomo et al. 2003). This has led to an active search for environmental exposures that modulate normal neurodevelopment. From such efforts, polychlorinated biphenyls (PCBs) have emerged as a credible risk factor for neurodevelopmental disorders (Tilson and Kodavanti 1998). A recent analysis of epidemiologic data concluded that the weight of evidence indicates a negative association between developmental exposure to environmental PCB levels and measures of neuropsychological function in infancy or childhood (Schantz et al. 2003). Combined in utero and lactational PCB exposure correlates with decreased IQ scores, psychomotor difficulties, impaired learning and memory, and attentional deficits. Findings from experimental animal models are consistent with those in humans including deficits in learning/memory (Hany et al. 1999; Sable et al. 2006; Schantz et al. 1989; Widholm et al. 2004) and sensorimotor (Nguon et al. 2005; Powers et al. 2006; Roegge et al. 2004) functions.

The cell and molecular mechanism(s) by which PCBs derail cognitive and psychomotor development in children remain speculative. Although experimental animal and cell culture studies have identified specific signaling pathways disrupted by developmental PCB exposure [reviewed by Kodavanti (2005)], how these molecular changes relate to functional deficits has been difficult to establish, in part because of the paucity of data describing effects of PCBs on specific neurodevelopmental events. It is postulated that PCB-induced neuropsychological deficits reflect altered patterns of neuronal connectivity (Gilbert et al. 2000; Seegal 1996). A critical determinant of neuronal connectivity is dendritic morphology. The size of the dendritic arbor and the density of dendritic spines determine the total synaptic input a neuron can receive (Engert and Bonhoeffer 1999; Purves 1988) and influence the types and distribution of these inputs (Miller and Jacobs 1984; Schuman 1997; Sejnowski 1997). …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited article

Ontogenetic Alterations in Molecular and Structural Correlates of Dendritic Growth after Developmental Exposure to Polychlorinated Biphenyls
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen
Items saved from this article
  • Highlights & Notes
  • Citations
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Search by... Author
    Show... All Results Primary Sources Peer-reviewed

    Oops!

    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.