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Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats.

Castillo-Gómez E, Varea E, Blasco-Ibáñez JM, Crespo C, Nacher J - Neural Plast. (2016)

Bottom Line: Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation.Endo-N also reduced the expression of vesicular glutamate transporter-1.These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology Unit, BIOTECMED, Cell Biology Department, Universitat de València, 46100 Burjassot, Spain.

ABSTRACT
Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found.

No MeSH data available.


Related in: MedlinePlus

Graphs showing changes in the neuropil of VGLUT1 in the mPFC (a), dorsal cingulate (b), ventral cingulate (c), infralimbic (d), and prelimbic (e) cortices after Endo-N and/or PPHT treatments. Three sections per animal (n = 6 animals/group) were examined under bright-field illumination, homogeneously lighted, and digitalized using a CCD camera at 20x magnification. Grey levels were converted to optical densities (OD) using Image J software (NIH) (see Materials and Methods). Error bars represent SEM and asterisks in bars indicate statistically significant differences between groups after univariate repeated measures ANOVA followed by multiple pairwise comparisons with Bonferroni's correction (∗p < 0.05,  ∗∗p < 0.01, and ∗∗∗p < 0.001).
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fig2: Graphs showing changes in the neuropil of VGLUT1 in the mPFC (a), dorsal cingulate (b), ventral cingulate (c), infralimbic (d), and prelimbic (e) cortices after Endo-N and/or PPHT treatments. Three sections per animal (n = 6 animals/group) were examined under bright-field illumination, homogeneously lighted, and digitalized using a CCD camera at 20x magnification. Grey levels were converted to optical densities (OD) using Image J software (NIH) (see Materials and Methods). Error bars represent SEM and asterisks in bars indicate statistically significant differences between groups after univariate repeated measures ANOVA followed by multiple pairwise comparisons with Bonferroni's correction (∗p < 0.05,  ∗∗p < 0.01, and ∗∗∗p < 0.001).

Mentions: For VGLUT1 neuropil expression (Figures 2(a)–2(e)), repeated measures ANOVA test showed significant main effects of treatment (F3,18 = 9.689, p < 0.001), region (F3,16 = 6.829, p = 0.004), and layer (F4,15 = 168.327, p < 0.001). Consequently, multiple pairwise comparisons with Bonferroni's correction were performed in order to compare treatment effect on the whole mPFC between pairs of experimental groups. Our results indicate that VGLUT1 expression in the mPFC neuropil was not affected by PPHT treatment, neither in the presence nor in the absence of PSA (Control/Control versus Control/PPHT or Endo-N/Control versus Endo-N/PPHT: p = 1.000), but PSA depletion by itself decreased it (Control/Control versus Endo-N/Control: p = 0.028; Control/Control versus Endo-N/PPHT: p = 0.004) (Figure 2(a)).


Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats.

Castillo-Gómez E, Varea E, Blasco-Ibáñez JM, Crespo C, Nacher J - Neural Plast. (2016)

Graphs showing changes in the neuropil of VGLUT1 in the mPFC (a), dorsal cingulate (b), ventral cingulate (c), infralimbic (d), and prelimbic (e) cortices after Endo-N and/or PPHT treatments. Three sections per animal (n = 6 animals/group) were examined under bright-field illumination, homogeneously lighted, and digitalized using a CCD camera at 20x magnification. Grey levels were converted to optical densities (OD) using Image J software (NIH) (see Materials and Methods). Error bars represent SEM and asterisks in bars indicate statistically significant differences between groups after univariate repeated measures ANOVA followed by multiple pairwise comparisons with Bonferroni's correction (∗p < 0.05,  ∗∗p < 0.01, and ∗∗∗p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Graphs showing changes in the neuropil of VGLUT1 in the mPFC (a), dorsal cingulate (b), ventral cingulate (c), infralimbic (d), and prelimbic (e) cortices after Endo-N and/or PPHT treatments. Three sections per animal (n = 6 animals/group) were examined under bright-field illumination, homogeneously lighted, and digitalized using a CCD camera at 20x magnification. Grey levels were converted to optical densities (OD) using Image J software (NIH) (see Materials and Methods). Error bars represent SEM and asterisks in bars indicate statistically significant differences between groups after univariate repeated measures ANOVA followed by multiple pairwise comparisons with Bonferroni's correction (∗p < 0.05,  ∗∗p < 0.01, and ∗∗∗p < 0.001).
Mentions: For VGLUT1 neuropil expression (Figures 2(a)–2(e)), repeated measures ANOVA test showed significant main effects of treatment (F3,18 = 9.689, p < 0.001), region (F3,16 = 6.829, p = 0.004), and layer (F4,15 = 168.327, p < 0.001). Consequently, multiple pairwise comparisons with Bonferroni's correction were performed in order to compare treatment effect on the whole mPFC between pairs of experimental groups. Our results indicate that VGLUT1 expression in the mPFC neuropil was not affected by PPHT treatment, neither in the presence nor in the absence of PSA (Control/Control versus Control/PPHT or Endo-N/Control versus Endo-N/PPHT: p = 1.000), but PSA depletion by itself decreased it (Control/Control versus Endo-N/Control: p = 0.028; Control/Control versus Endo-N/PPHT: p = 0.004) (Figure 2(a)).

Bottom Line: Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation.Endo-N also reduced the expression of vesicular glutamate transporter-1.These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology Unit, BIOTECMED, Cell Biology Department, Universitat de València, 46100 Burjassot, Spain.

ABSTRACT
Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found.

No MeSH data available.


Related in: MedlinePlus