A single link to the first track to allow the export script to build the search page
  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    753—Neuroendocrine Anatomy and Physiology

    Wednesday, November 13, 2013, 8:00 am - 12:00 noon

    753.11: Advanced pubertal timing in female rhesus macaques with neonatal amygdala lesions

    Location: Halls B-H

    ">*S. B. STEPHENS1,2, J. RAPER1,2, J. BACHEVALIER1,2, K. WALLEN1,2;
    1Psychology, Emory Univ., ATLANTA, GA; 2Yerkes Natl. Primate Res. Ctr., Atlanta, GA

    Abstract Body: Puberty is initiated by cyclic release of hypothalamic gonadotropin-releasing hormone (GnRH) culminating in adult reproductive function (Plant, 2001). Despite a trend for earlier puberty in girls (McDowell et al., 2007), there is considerable variation in pubertal timing (Marshall & Tanner, 1969). Social context influences variation in pubertal timing, such as social rank accelerating or delaying menarche or first ovulation in nonhuman primates (Zehr et al., 2005; Wilson et al., 2013). The brain mechanisms monitoring the social environment that interact with the HPG axis to time puberty onset are unknown. The amygdala is important for responses to social information (Petrulis & Johnston, 1999; Spiteri et al., 2010). Amygdala damage in rats altered pubertal timing (Döcke, 1981), indicating the amygdala potentially mediates the effects of social context on pubertal timing. We examined the influence of neonatal amygdala lesions on pubertal timing in female rhesus macaques living in large, social groups. Subjects received bilateral, neurotoxic amygdala lesions (Neo-A) or sham treatments (Neo-C) at 1mo. Beginning at 14-17mo, vaginal swabs and blood were collected at least 3 days/week from Aug-Apr to detect menarche and 1st ovulation. Lesion status significantly predicted age at menarche, β= -.60, t(14)= -2.81, p= .01, accounting for 36% of the variance in menarchal age, R2= .36, F(1,15)= 7.88, p= .01. Significantly more lesioned females experienced menarche at 1.5 years of age compared to control females, X2= 5.7, p= .02. Social rank was unrelated to menarchal age in Neo-C females, r(9)= .27, p= .48, but was related to menarchal age in Neo-A females, r(7)= .82, p= .02. However, social rank was related to right amygdala damage, r(7)= -.91, p= .004, as well as age at menarche, r(7)= -.82, p= .02. Thus, the independent effects of right amygdala damage or social rank on age at menarche are unclear. Treatment significantly predicted age at first ovulation, accounting for 30% of the variance in age at first ovulation, β= -.54, t(13)= -2.33, p= .04; R2= .30, F(1,14)= 5.43, p= .04. Lesioned females (CV=39.00) had greater variation in age at first ovulation compared to control females (CV= 16.69), F(1,13)= 5.46, p= .04. Social rank was unrelated to age at first ovulation in Neo-C females, r(9)= .33, p= .38, or in Neo-A females, r(6)= .57, p= .24. Though these data do not support the hypothesis that the amygdala mediates social context and pubertal timing, the data support an inhibitory influence of the amygdala on puberty onset, possibly involving GABA inhibition of the HPG axis.
    National Institute of Mental Health (MH050268) & Office of Research Infrastructure Programs/OD P51OD11132.

    Lay Language Summary: Our research demonstrated that damage early in life to a part of the brain known to modulate emotional regulation and memory, the amygdala, hastened puberty onset in female rhesus monkeys. The influence of the amygdala was specific to puberty onset as it did not affect the duration of puberty, the time between puberty onset and reproductive maturation.
    In recent decades, there has been a decline in the age at menarche in girls that is thought to result from greater body weight at an earlier age. Though age at menarche is declining in the population, there exists considerable individual variation in the age of puberty onset. Social context is one source of this variation. For example, parental divorce or presence of a new stepfather leads to earlier menarche in girls. However, the mechanism(s) by which social context influences pubertal timing are unknown. The amygdala, a brain structure located in the temporal lobe, is important for integrating social contextual information and represents a likely candidate to integrate social signals and modulate pubertal timing. Our results indicate that the amygdala delays the start of puberty, such that amygdala damage in early infancy has effects similar to those observed after profound changes in social context.
    To examine the influence of the amygdala on pubertal timing, female rhesus monkeys received either damage to amygdala at one month of age, when the amygdala is still maturing, or no amygdala damage. Age at menarche, indicative of puberty onset, was determined for each female by checking for menstruation. To determine the age at first ovulation, or reproductive maturation, blood samples were collected to measure the hormone progesterone, which increases markedly after ovulation. Females were reared in large species-typical social groups with their mothers, siblings, and adult males allowing us to examine the effects of social rank on puberty onset and whether amygdala damage eliminated the effects of social context on pubertal timing.
    Females with amygdala damage early in life experienced earlier menarche and first ovulation than did females with no amygdala damage. Earlier puberty following damage to the amygdala was not the result of greater body weight as females with amygdala damage did not weigh more prior to menarche than did females without amygdala damage. We found no relationship between social rank and age at menarche or first ovulation in females without amygdala damage and thus, it is not clear how damage to the amygdala might alter the relationship between social rank and pubertal timing. Damage to the amygdala did not influence the length of the pubertal period indicating that earlier puberty onset did not lead to a shorter or longer duration of puberty.
    These results suggest that the amygdala has an inhibitory influence on puberty onset in females that is not affected by greater body weight. Damage to the amygdala early in life interferes with this inhibitory influence, resulting in earlier puberty onset. Based on our data, it is possible that social context may affect pubertal timing by reducing or enhancing the amygdala’s inhibitory effect. Future research is needed to understand the specific mechanisms by which the amygdala influences puberty onset and to determine whether the amygdala modulates the effects of social context on pubertal timing.
    The hypothalamus was thought to be the critical brain region regulating reproduction, with research regarding the mechanisms of puberty onset focusing on the hypothalamus. However, the present data demonstrate the critical role played by a brain region outside of the hypothalamus, the amygdala, in puberty onset and begin to provide a better understanding of the mechanisms involved in pubertal timing, as well as how social contextual information may alter pubertal timing.

    Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    753—Neuroendocrine Anatomy and Physiology

    Wednesday, November 13, 2013, 8:00 am - 12:00 noon

    753.11: Advanced pubertal timing in female rhesus macaques with neonatal amygdala lesions

    Location: Halls B-H

    ">*S. B. STEPHENS1,2, J. RAPER1,2, J. BACHEVALIER1,2, K. WALLEN1,2;
    1Psychology, Emory Univ., ATLANTA, GA; 2Yerkes Natl. Primate Res. Ctr., Atlanta, GA

    Abstract Body: Puberty is initiated by cyclic release of hypothalamic gonadotropin-releasing hormone (GnRH) culminating in adult reproductive function (Plant, 2001). Despite a trend for earlier puberty in girls (McDowell et al., 2007), there is considerable variation in pubertal timing (Marshall & Tanner, 1969). Social context influences variation in pubertal timing, such as social rank accelerating or delaying menarche or first ovulation in nonhuman primates (Zehr et al., 2005; Wilson et al., 2013). The brain mechanisms monitoring the social environment that interact with the HPG axis to time puberty onset are unknown. The amygdala is important for responses to social information (Petrulis & Johnston, 1999; Spiteri et al., 2010). Amygdala damage in rats altered pubertal timing (Döcke, 1981), indicating the amygdala potentially mediates the effects of social context on pubertal timing. We examined the influence of neonatal amygdala lesions on pubertal timing in female rhesus macaques living in large, social groups. Subjects received bilateral, neurotoxic amygdala lesions (Neo-A) or sham treatments (Neo-C) at 1mo. Beginning at 14-17mo, vaginal swabs and blood were collected at least 3 days/week from Aug-Apr to detect menarche and 1st ovulation. Lesion status significantly predicted age at menarche, β= -.60, t(14)= -2.81, p= .01, accounting for 36% of the variance in menarchal age, R2= .36, F(1,15)= 7.88, p= .01. Significantly more lesioned females experienced menarche at 1.5 years of age compared to control females, X2= 5.7, p= .02. Social rank was unrelated to menarchal age in Neo-C females, r(9)= .27, p= .48, but was related to menarchal age in Neo-A females, r(7)= .82, p= .02. However, social rank was related to right amygdala damage, r(7)= -.91, p= .004, as well as age at menarche, r(7)= -.82, p= .02. Thus, the independent effects of right amygdala damage or social rank on age at menarche are unclear. Treatment significantly predicted age at first ovulation, accounting for 30% of the variance in age at first ovulation, β= -.54, t(13)= -2.33, p= .04; R2= .30, F(1,14)= 5.43, p= .04. Lesioned females (CV=39.00) had greater variation in age at first ovulation compared to control females (CV= 16.69), F(1,13)= 5.46, p= .04. Social rank was unrelated to age at first ovulation in Neo-C females, r(9)= .33, p= .38, or in Neo-A females, r(6)= .57, p= .24. Though these data do not support the hypothesis that the amygdala mediates social context and pubertal timing, the data support an inhibitory influence of the amygdala on puberty onset, possibly involving GABA inhibition of the HPG axis.
    National Institute of Mental Health (MH050268) & Office of Research Infrastructure Programs/OD P51OD11132.

    Lay Language Summary: Our research demonstrated that damage early in life to a part of the brain known to modulate emotional regulation and memory, the amygdala, hastened puberty onset in female rhesus monkeys. The influence of the amygdala was specific to puberty onset as it did not affect the duration of puberty, the time between puberty onset and reproductive maturation.
    In recent decades, there has been a decline in the age at menarche in girls that is thought to result from greater body weight at an earlier age. Though age at menarche is declining in the population, there exists considerable individual variation in the age of puberty onset. Social context is one source of this variation. For example, parental divorce or presence of a new stepfather leads to earlier menarche in girls. However, the mechanism(s) by which social context influences pubertal timing are unknown. The amygdala, a brain structure located in the temporal lobe, is important for integrating social contextual information and represents a likely candidate to integrate social signals and modulate pubertal timing. Our results indicate that the amygdala delays the start of puberty, such that amygdala damage in early infancy has effects similar to those observed after profound changes in social context.
    To examine the influence of the amygdala on pubertal timing, female rhesus monkeys received either damage to amygdala at one month of age, when the amygdala is still maturing, or no amygdala damage. Age at menarche, indicative of puberty onset, was determined for each female by checking for menstruation. To determine the age at first ovulation, or reproductive maturation, blood samples were collected to measure the hormone progesterone, which increases markedly after ovulation. Females were reared in large species-typical social groups with their mothers, siblings, and adult males allowing us to examine the effects of social rank on puberty onset and whether amygdala damage eliminated the effects of social context on pubertal timing.
    Females with amygdala damage early in life experienced earlier menarche and first ovulation than did females with no amygdala damage. Earlier puberty following damage to the amygdala was not the result of greater body weight as females with amygdala damage did not weigh more prior to menarche than did females without amygdala damage. We found no relationship between social rank and age at menarche or first ovulation in females without amygdala damage and thus, it is not clear how damage to the amygdala might alter the relationship between social rank and pubertal timing. Damage to the amygdala did not influence the length of the pubertal period indicating that earlier puberty onset did not lead to a shorter or longer duration of puberty.
    These results suggest that the amygdala has an inhibitory influence on puberty onset in females that is not affected by greater body weight. Damage to the amygdala early in life interferes with this inhibitory influence, resulting in earlier puberty onset. Based on our data, it is possible that social context may affect pubertal timing by reducing or enhancing the amygdala’s inhibitory effect. Future research is needed to understand the specific mechanisms by which the amygdala influences puberty onset and to determine whether the amygdala modulates the effects of social context on pubertal timing.
    The hypothalamus was thought to be the critical brain region regulating reproduction, with research regarding the mechanisms of puberty onset focusing on the hypothalamus. However, the present data demonstrate the critical role played by a brain region outside of the hypothalamus, the amygdala, in puberty onset and begin to provide a better understanding of the mechanisms involved in pubertal timing, as well as how social contextual information may alter pubertal timing.