Limits...
Modulation of social behavior by the agouti pigmentation gene.

Carola V, Perlas E, Zonfrillo F, Soini HA, Novotny MV, Gross CT - Front Behav Neurosci (2014)

Bottom Line: Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors.Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin.These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

View Article: PubMed Central - PubMed

Affiliation: IRCCS Fondazione Santa Lucia Rome, Italy ; Mouse Biology Unit, European Molecular Biology Laboratory Monterotondo, Italy.

ABSTRACT
Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti) have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

No MeSH data available.


Related in: MedlinePlus

Secretion from preputial gland is different between non-agouti and agouti mice. (A) Non-agouti mice showed significant higher levels of 1-hexadecylacetate, carvomenthene, 1-heptadecylacetate and lower levels of indane and A methylindan-1 in the preputial glands compared to agouti mice. (B–F) Correlation analyses performed between the levels of these compounds (normalized peak area) and the preference for the urine-containing compartment (social side) measured in the same mice in the olfactory approach test, showed that the levels of heptadecylacetate, indane, and A methylindan-1 were significantly correlated with this behavior. (N = 11; *P < 0.05, **P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4117936&req=5

Figure 3: Secretion from preputial gland is different between non-agouti and agouti mice. (A) Non-agouti mice showed significant higher levels of 1-hexadecylacetate, carvomenthene, 1-heptadecylacetate and lower levels of indane and A methylindan-1 in the preputial glands compared to agouti mice. (B–F) Correlation analyses performed between the levels of these compounds (normalized peak area) and the preference for the urine-containing compartment (social side) measured in the same mice in the olfactory approach test, showed that the levels of heptadecylacetate, indane, and A methylindan-1 were significantly correlated with this behavior. (N = 11; *P < 0.05, **P < 0.01).

Mentions: To examine whether agouti genotype might have an effect on social behavior by altering the production of pheromone-like substances in the preputial gland, we used SBSE/GC-mass spectrometry to quantify VOC from preputial glands collected from agouti and non-agouti mice following testing in the olfactory approach test. VOC profiles obtained by the method contained about 100 compounds of which 21 could be identified and their normalized levels compared quantitatively (Table S1). We observed that non-agouti mice had higher levels of 1-hexadecylacetate [ANOVA, genotype effect: F(1, 10) = 7.58, P = 0.022], a compound found in higher quantities in males than females and reported to promote social investigation in a dose and sex-dependent manner (Zhang et al., 2007, 2008; Figure 3A). We also found higher levels of carvomenthene [ANOVA, genotype effect: F(1, 10) = 6.25, P = 0.040] and 1-heptadecylacetate [ANOVA, genotype effect: F(1, 10) = 17.22, P = 0.002] and lower levels of indane [ANOVA, genotype effect: F(1, 10) = 10.55, P = 0.040] and A methylindan-1 [ANOVA, genotype effect: F(1, 10) = 8.67, P = 0.016] in non-agouti compared to agouti mice (Figure 3A). Absolute levels of some (1-heptadecylacetate, indane, A methylindan-1), but not all of these compounds were significantly correlated with exploratory behavior in the olfactory approach test across animals (Figures 3B–G) consistent with a possible causal link between preputial gland volatile production and social behavior.


Modulation of social behavior by the agouti pigmentation gene.

Carola V, Perlas E, Zonfrillo F, Soini HA, Novotny MV, Gross CT - Front Behav Neurosci (2014)

Secretion from preputial gland is different between non-agouti and agouti mice. (A) Non-agouti mice showed significant higher levels of 1-hexadecylacetate, carvomenthene, 1-heptadecylacetate and lower levels of indane and A methylindan-1 in the preputial glands compared to agouti mice. (B–F) Correlation analyses performed between the levels of these compounds (normalized peak area) and the preference for the urine-containing compartment (social side) measured in the same mice in the olfactory approach test, showed that the levels of heptadecylacetate, indane, and A methylindan-1 were significantly correlated with this behavior. (N = 11; *P < 0.05, **P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4117936&req=5

Figure 3: Secretion from preputial gland is different between non-agouti and agouti mice. (A) Non-agouti mice showed significant higher levels of 1-hexadecylacetate, carvomenthene, 1-heptadecylacetate and lower levels of indane and A methylindan-1 in the preputial glands compared to agouti mice. (B–F) Correlation analyses performed between the levels of these compounds (normalized peak area) and the preference for the urine-containing compartment (social side) measured in the same mice in the olfactory approach test, showed that the levels of heptadecylacetate, indane, and A methylindan-1 were significantly correlated with this behavior. (N = 11; *P < 0.05, **P < 0.01).
Mentions: To examine whether agouti genotype might have an effect on social behavior by altering the production of pheromone-like substances in the preputial gland, we used SBSE/GC-mass spectrometry to quantify VOC from preputial glands collected from agouti and non-agouti mice following testing in the olfactory approach test. VOC profiles obtained by the method contained about 100 compounds of which 21 could be identified and their normalized levels compared quantitatively (Table S1). We observed that non-agouti mice had higher levels of 1-hexadecylacetate [ANOVA, genotype effect: F(1, 10) = 7.58, P = 0.022], a compound found in higher quantities in males than females and reported to promote social investigation in a dose and sex-dependent manner (Zhang et al., 2007, 2008; Figure 3A). We also found higher levels of carvomenthene [ANOVA, genotype effect: F(1, 10) = 6.25, P = 0.040] and 1-heptadecylacetate [ANOVA, genotype effect: F(1, 10) = 17.22, P = 0.002] and lower levels of indane [ANOVA, genotype effect: F(1, 10) = 10.55, P = 0.040] and A methylindan-1 [ANOVA, genotype effect: F(1, 10) = 8.67, P = 0.016] in non-agouti compared to agouti mice (Figure 3A). Absolute levels of some (1-heptadecylacetate, indane, A methylindan-1), but not all of these compounds were significantly correlated with exploratory behavior in the olfactory approach test across animals (Figures 3B–G) consistent with a possible causal link between preputial gland volatile production and social behavior.

Bottom Line: Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors.Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin.These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

View Article: PubMed Central - PubMed

Affiliation: IRCCS Fondazione Santa Lucia Rome, Italy ; Mouse Biology Unit, European Molecular Biology Laboratory Monterotondo, Italy.

ABSTRACT
Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti) have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

No MeSH data available.


Related in: MedlinePlus