Limits...
Targeted deletion of Vglut2 expression in the embryonal telencephalon promotes an anxiolytic phenotype of the adult mouse.

Nordenankar K, Bergfors A, Wallén-Mackenzie Å - Ups. J. Med. Sci. (2015)

Bottom Line: Anxiety is a natural emotion experienced by all individuals.Anxiolysis, the reduction of anxiety, is mediated via several large groups of therapeutical compounds, but the relief is often only temporary, and increased knowledge of the neurobiology underlying anxiety is needed in order to improve future therapies.Our results suggest that both embryonal and adolescent forebrain expression of Vglut2 normally contributes to balancing the level of anxiety.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Unit of Functional Neurobiology and Unit of Developmental Genetics, Uppsala University , Box 593, S-75214 Uppsala , Sweden.

ABSTRACT

Background: Anxiety is a natural emotion experienced by all individuals. However, when anxiety becomes excessive, it contributes to the substantial group of anxiety disorders that affect one in three people and thus are among the most common psychiatric disorders. Anxiolysis, the reduction of anxiety, is mediated via several large groups of therapeutical compounds, but the relief is often only temporary, and increased knowledge of the neurobiology underlying anxiety is needed in order to improve future therapies.

Aim: We previously demonstrated that mice lacking forebrain expression of the Vesicular glutamate transporter 2 (Vglut2) from adolescence showed a strong anxiolytic behaviour as adults. In the current study, we wished to analyse if removal of Vglut2 expression already from mid-gestation of the mouse embryo would give rise to similar anxiolysis in the adult mouse.

Methods: We produced transgenic mice lacking Vglut2 from mid-gestation and analysed their affective behaviour, including anxiety, when they had reached adulthood.

Results: The transgenic mice lacking Vglut2 expression from mid-gestation showed certain signs of anxiolytic behaviour, but this phenotype was not as prominent as when Vglut2 was removed during adolescence.

Conclusion: Our results suggest that both embryonal and adolescent forebrain expression of Vglut2 normally contributes to balancing the level of anxiety. As the neurobiological basis for anxiety is similar across species, our results in mice may help improve the current understanding of the neurocircuitry of anxiety, and hence anxiolysis, also in humans.

No MeSH data available.


Related in: MedlinePlus

Verification that the overall gross anatomy is normal in the Vglut2f/f;Emx1-Cre mice compared to control mice. Floating in situ hybridization on coronal brain (70 μm) sections from control and Vglut2f/f;Emx1-Cre cKO mice using a DIG-labelled Viaat (A, B) or Vglut1(C–H) probe. Close-ups show that ACo and BM do not express Vglut1 mRNA, while BL and part of Me express Vglut1 mRNA. ACo = anterior cortical amygdaloid area; BL = basolateral amygdaloid nucleus; BM = basomedial amygdaloid nucleus anterior part; Me = medial amygdaloid nucleus. Bregma interval (dorsal, ventral) is shown in lower right corner.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526870&req=5

Figure 2: Verification that the overall gross anatomy is normal in the Vglut2f/f;Emx1-Cre mice compared to control mice. Floating in situ hybridization on coronal brain (70 μm) sections from control and Vglut2f/f;Emx1-Cre cKO mice using a DIG-labelled Viaat (A, B) or Vglut1(C–H) probe. Close-ups show that ACo and BM do not express Vglut1 mRNA, while BL and part of Me express Vglut1 mRNA. ACo = anterior cortical amygdaloid area; BL = basolateral amygdaloid nucleus; BM = basomedial amygdaloid nucleus anterior part; Me = medial amygdaloid nucleus. Bregma interval (dorsal, ventral) is shown in lower right corner.

Mentions: To verify that the overall brain anatomy was normal in the Vglut2f/f;Emx1-Cre(tg/wt) cKO mice, ISH analysis of one additional glutamatergic marker, Vglut1, and of one marker for inhibitory neurons, the vesicular amino acid transporter (Viaat), was performed. In contrast to the restricted expression of Vglut2 in the telencephalon, Vglut1 is prominently expressed in this area (7,9,11-13,38). Strong Vglut1 expression was found throughout the neocortex and hippocampal formation and also in several subnuclei of the amygdala complex (Figure 2A, C), which is in accordance with previous studies. Vglut1 was most prominently expressed in the BL, BM, and Me nuclei of the amygdala. No altered distribution was seen in the cKO brains (Figure 2B, D; and data not shown). Further, expression of Vglut1 in the mid-brain, cerebellum, and pons appeared normal in the cKO brains compared to controls (Figure 2E, F). Viaat expression was also detected, as expected, in inhibitory populations and appeared normal in the cKO brain compared to controls (Figure 2G, H). Together, these results showed normal cellular distribution of excitatory and inhibitory populations in the Vglut2f/f;Emx1-Cre(tg/wt) cKO mice, and although this was not quantitative, by ISH analysis, we did not detect differences in expression levels in these areas.


Targeted deletion of Vglut2 expression in the embryonal telencephalon promotes an anxiolytic phenotype of the adult mouse.

Nordenankar K, Bergfors A, Wallén-Mackenzie Å - Ups. J. Med. Sci. (2015)

Verification that the overall gross anatomy is normal in the Vglut2f/f;Emx1-Cre mice compared to control mice. Floating in situ hybridization on coronal brain (70 μm) sections from control and Vglut2f/f;Emx1-Cre cKO mice using a DIG-labelled Viaat (A, B) or Vglut1(C–H) probe. Close-ups show that ACo and BM do not express Vglut1 mRNA, while BL and part of Me express Vglut1 mRNA. ACo = anterior cortical amygdaloid area; BL = basolateral amygdaloid nucleus; BM = basomedial amygdaloid nucleus anterior part; Me = medial amygdaloid nucleus. Bregma interval (dorsal, ventral) is shown in lower right corner.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526870&req=5

Figure 2: Verification that the overall gross anatomy is normal in the Vglut2f/f;Emx1-Cre mice compared to control mice. Floating in situ hybridization on coronal brain (70 μm) sections from control and Vglut2f/f;Emx1-Cre cKO mice using a DIG-labelled Viaat (A, B) or Vglut1(C–H) probe. Close-ups show that ACo and BM do not express Vglut1 mRNA, while BL and part of Me express Vglut1 mRNA. ACo = anterior cortical amygdaloid area; BL = basolateral amygdaloid nucleus; BM = basomedial amygdaloid nucleus anterior part; Me = medial amygdaloid nucleus. Bregma interval (dorsal, ventral) is shown in lower right corner.
Mentions: To verify that the overall brain anatomy was normal in the Vglut2f/f;Emx1-Cre(tg/wt) cKO mice, ISH analysis of one additional glutamatergic marker, Vglut1, and of one marker for inhibitory neurons, the vesicular amino acid transporter (Viaat), was performed. In contrast to the restricted expression of Vglut2 in the telencephalon, Vglut1 is prominently expressed in this area (7,9,11-13,38). Strong Vglut1 expression was found throughout the neocortex and hippocampal formation and also in several subnuclei of the amygdala complex (Figure 2A, C), which is in accordance with previous studies. Vglut1 was most prominently expressed in the BL, BM, and Me nuclei of the amygdala. No altered distribution was seen in the cKO brains (Figure 2B, D; and data not shown). Further, expression of Vglut1 in the mid-brain, cerebellum, and pons appeared normal in the cKO brains compared to controls (Figure 2E, F). Viaat expression was also detected, as expected, in inhibitory populations and appeared normal in the cKO brain compared to controls (Figure 2G, H). Together, these results showed normal cellular distribution of excitatory and inhibitory populations in the Vglut2f/f;Emx1-Cre(tg/wt) cKO mice, and although this was not quantitative, by ISH analysis, we did not detect differences in expression levels in these areas.

Bottom Line: Anxiety is a natural emotion experienced by all individuals.Anxiolysis, the reduction of anxiety, is mediated via several large groups of therapeutical compounds, but the relief is often only temporary, and increased knowledge of the neurobiology underlying anxiety is needed in order to improve future therapies.Our results suggest that both embryonal and adolescent forebrain expression of Vglut2 normally contributes to balancing the level of anxiety.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Unit of Functional Neurobiology and Unit of Developmental Genetics, Uppsala University , Box 593, S-75214 Uppsala , Sweden.

ABSTRACT

Background: Anxiety is a natural emotion experienced by all individuals. However, when anxiety becomes excessive, it contributes to the substantial group of anxiety disorders that affect one in three people and thus are among the most common psychiatric disorders. Anxiolysis, the reduction of anxiety, is mediated via several large groups of therapeutical compounds, but the relief is often only temporary, and increased knowledge of the neurobiology underlying anxiety is needed in order to improve future therapies.

Aim: We previously demonstrated that mice lacking forebrain expression of the Vesicular glutamate transporter 2 (Vglut2) from adolescence showed a strong anxiolytic behaviour as adults. In the current study, we wished to analyse if removal of Vglut2 expression already from mid-gestation of the mouse embryo would give rise to similar anxiolysis in the adult mouse.

Methods: We produced transgenic mice lacking Vglut2 from mid-gestation and analysed their affective behaviour, including anxiety, when they had reached adulthood.

Results: The transgenic mice lacking Vglut2 expression from mid-gestation showed certain signs of anxiolytic behaviour, but this phenotype was not as prominent as when Vglut2 was removed during adolescence.

Conclusion: Our results suggest that both embryonal and adolescent forebrain expression of Vglut2 normally contributes to balancing the level of anxiety. As the neurobiological basis for anxiety is similar across species, our results in mice may help improve the current understanding of the neurocircuitry of anxiety, and hence anxiolysis, also in humans.

No MeSH data available.


Related in: MedlinePlus