A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration
Abstract
:1. Introduction
2. Results
2.1. Gene Expression Analysis: Comparison between Experimental Groups in Homer1a mRNA Levels
2.2. Generation and Comparison of the Correlation Matrices for the Connectivity Analysis
2.3. Construction and Comparison of the Brain Networks
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Drug Treatment and Study Design
4.3. In Situ Hybridization Histochemistry (ISHH)
4.4. Image Analysis
4.5. Statistical Analysis
Comparison of the Correlation Matrices and Generation of Networks
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Abbreviation | Brain Region |
---|---|
LSV | Lateral septal nucleus, ventral |
Tu | Olfactory tubercle |
LSD | Lateral septal nucleus, dorsal |
LSI | Lateral septal nucleus, intermediate |
Icj | Islands of Calleja |
VP | Ventral pallidum |
Shi | Septohippocampal nucleus |
MS | Medial septum |
VDB | Nucleus of the vertical limb of the diagonal band |
IG | Indusium griseum |
S1dz | Somatosensory 1, dysgranular zone |
AIV | Agranular insular area, ventral |
S1ULp | Upper lip of the primary somatosensory cortex |
GI | Granular insular cortex |
DI | Dysgranular insular cortex |
AcSh | Accumbens nucleus, shell |
Pir | Piriform cortex |
AID | Agranular insular area, dorsal |
LSS | Lateral stripe of striatum |
Cg2 | Cingulate cortex, area 2 |
CPDL | Dorsolateral caudate putamen |
CPVL | Ventrolateral caudate putamen |
CPVM | Ventromedial caudate putamen |
Cg1 | Cingulate cortex, area 1 |
M2 | Supplementary motor cortex |
CPDM | Dorsomedial caudate putamen |
Den | Dorsal endopiriform nucleus |
M1 | Primary motor cortex |
S1Fl | Somatosensory 1, forelimb region |
AcCo | Accumbens nucleus, core |
Cl | Claustrum |
S1j | Somatosensory 1, jaw region |
S1jO | Primary somatosensory cortex, jaw region, oral surface |
ROIs | t | Degree of Freedom | p-Value | Confidence Interval | |
---|---|---|---|---|---|
Inferior | Superior | ||||
Ig | 1.29 | 8 | 0.234 | −0.31 | 0.11 |
Cg2 | −3.48 | 8 | 0.008 | −0.47 | −0.96 |
Cg1 | −4.43 | 8 | 0.002 | −0.64 | −0.20 |
M2 | −3.56 | 8 | 0.007 | −0.59 | −0.13 |
M1 | −3.47 | 8 | 0.008 | −0.51 | −0.10 |
S1FL | −3.22 | 8 | 0.012 | −0.44 | −0.73 |
S1j | −2.59 | 8 | 0.032 | −0.38 | −0.02 |
S1jO | 0.05 | 8 | 0.961 | −0.76 | 0.79 |
S1DZ | −2.28 | 8 | 0.052 | −0.37 | 0.00 |
S1ULp | −1.22 | 8 | 0.259 | −0.27 | 0.08 |
GI | −1.03 | 8 | 0.335 | −0.35 | 0.14 |
DI | −0.70 | 8 | 0.506 | −0.26 | 0.14 |
AID | −0.45 | 8 | 0.662 | −0.28 | 0.19 |
AIV | −0.16 | 8 | 0.880 | −0.15 | 0.13 |
Cl | −0.97 | 8 | 0.363 | −0.30 | 0.12 |
Pir | −2.07 | 8 | 0.073 | −0.44 | 0.02 |
Den | −1.13 | 8 | 0.292 | −0.35 | 0.12 |
LSS | −1.48 | 8 | 0.176 | −0.32 | 0.07 |
CPDM | −3.14 | 8 | 0.014 | −0.53 | −0.08 |
CPDL | −3.63 | 8 | 0.007 | −0.56 | −0.12 |
CPVL | −2.93 | 8 | 0.019 | −0.53 | −0.64 |
CPVM | −4.09 | 8 | 0.003 | −0.66 | −0.18 |
AcCo | −2.74 | 8 | 0.026 | −0.48 | −0.04 |
AcSh | −2.45 | 8 | 0.040 | −0.56 | −0.02 |
LSD | −1.78 | 8 | 0.113 | −0.29 | 0.04 |
LSI | −1.47 | 8 | 0.180 | −0.26 | 0.06 |
LSV | −2.58 | 8 | 0.033 | −0.27 | −0.02 |
Shi | −2.19 | 8 | 0.060 | −0.26 | 0.01 |
MS | −2.14 | 8 | 0.065 | −0.24 | 0.01 |
VDB | −1.311 | 8 | 0.226 | −0.29 | 0.08 |
Icj | −3.55 | 8 | 0.007 | −0.24 | −0.05 |
VP | −4.21 | 8 | 0.003 | −0.35 | −0.10 |
Tu | −2.68 | 8 | 0.028 | −0.36 | −0.03 |
ROIs | t | Degree of Freedom | p-Value | Confidence Interval | |
---|---|---|---|---|---|
Inferior | Superior | ||||
Ig | 0.92 | 8 | 0.387 | −0.05 | 0.12 |
Cg2 | −2.43 | 8 | 0.041 | −0.36 | −0.01 |
Cg1 | −2.16 | 8 | 0.063 | −0.45 | 0.02 |
M2 | −1.92 | 8 | 0.091 | −0.40 | 0.04 |
M1 | −1.69 | 8 | 0.130 | −0.38 | 0.06 |
S1FL | −1.53 | 8 | 0.164 | −0.32 | 0.07 |
S1j | −1.28 | 8 | 0.235 | −0.30 | 0.09 |
S1jO | 0.42 | 8 | 0.687 | −0.76 | 1.09 |
S1DZ | −0.54 | 8 | 0.607 | −0.21 | 0.13 |
S1ULp | −0.10 | 8 | 0.925 | −0.18 | 0.17 |
GI | −0.43 | 8 | 0.677 | −0.31 | 0.21 |
DI | −0.14 | 8 | 0.889 | −0.23 | 0.20 |
AID | −0.42 | 8 | 0.686 | −0.26 | 0.18 |
AIV | −0.88 | 8 | 0.403 | −0.20 | 0.09 |
Cl | 1.69 | 8 | 0.129 | −0.06 | 0.39 |
Pir | −1.77 | 8 | 0.114 | −0.38 | 0.05 |
Den | 1.22 | 8 | 0.258 | −0.15 | 0.50 |
LSS | 0.92 | 8 | 0.386 | −0.14 | 0.32 |
CPDM | 1.22 | 8 | 0.256 | −0.12 | 0.40 |
CPDL | 2.07 | 8 | 0.073 | −0.03 | 0.48 |
CPVL | 1.81 | 8 | 0.108 | −0.06 | 0.51 |
CPVM | 0.17 | 8 | 0.867 | −0.25 | 0.29 |
AcCo | 0.13 | 8 | 0.901 | −0.24 | 0.27 |
AcSh | −0.12 | 8 | 0.912 | −0.28 | 0.25 |
LSD | −0.17 | 8 | 0.867 | −0.17 | 0.15 |
LSI | −0.04 | 8 | 0.968 | −0.15 | 0.15 |
LSV | −0.23 | 8 | 0.825 | −0.11 | 0.09 |
Shi | 0.33 | 8 | 0.749 | −0.16 | 0.21 |
MS | 0.46 | 8 | 0.657 | −0.16 | 0.24 |
VDB | 0.75 | 8 | 0.474 | −0.12 | 0.24 |
Icj | −0.44 | 8 | 0.669 | −0.17 | 0.12 |
VP | −2.67 | 8 | 0.028 | −0.23 | −0.02 |
Tu | −1.68 | 8 | 0.131 | −0.35 | 0.05 |
ROIs | t | Degree of Freedom | p-Value | Confidence Interval | |
---|---|---|---|---|---|
Inferior | Superior | ||||
Ig | −1.17 | 8 | 0.275 | −0.16 | 0.05 |
Cg2 | −3.00 | 8 | 0.017 | −0.40 | −0.05 |
Cg1 | −2.59 | 8 | 0.032 | −0.49 | −0.03 |
M2 | −2.89 | 8 | 0.020 | −0.52 | −0.06 |
M1 | −2.60 | 8 | 0.032 | −0.51 | −0.03 |
S1FL | −3.19 | 8 | 0.013 | −0.55 | −0.09 |
S1j | −2.32 | 8 | 0.049 | −0.53 | 0.00 |
S1jO | −1.73 | 8 | 0.121 | −0.69 | 0.10 |
S1DZ | −2.50 | 8 | 0.037 | −0.53 | −0.02 |
S1ULp | −2.30 | 8 | 0.051 | −0.55 | 0.00 |
GI | −2.52 | 8 | 0.036 | −0.61 | −0.03 |
DI | −3.21 | 8 | 0.012 | −0.66 | −0.11 |
AID | −3.42 | 8 | 0.009 | −0.63 | −0.12 |
AIV | −2.83 | 8 | 0.022 | −0.54 | −0.05 |
Cl | −2.94 | 8 | 0.019 | −0.55 | −0.07 |
Pir | −2.66 | 8 | 0.029 | −0.50 | −0.03 |
Den | −2.91 | 8 | 0.02 | −0.36 | −0.04 |
LSS | −3.28 | 8 | 0.011 | −0.58 | −0.10 |
CPDM | −5.41 | 8 | 0.001 | −0.52 | −0.21 |
CPDL | −6.24 | 8 | <0.001 | −0.7 | −0.32 |
CPVL | −6.93 | 8 | <0.001 | −0.84 | −0.42 |
CPVM | −4.32 | 8 | 0.003 | −0.71 | −0.21 |
AcCo | −3.36 | 8 | 0.01 | −0.58 | −0.11 |
AcSh | −3.49 | 8 | 0.008 | −0.63 | −0.13 |
LSD | −3.13 | 8 | 0.014 | −0.46 | −0.07 |
LSI | −2.90 | 8 | 0.02 | −0.26 | −0.03 |
LSV | −3.14 | 8 | 0.014 | −0.38 | −0.06 |
Shi | −3.58 | 8 | 0.007 | −0.36 | −0.08 |
MS | −4.84 | 8 | 0.001 | −0.29 | −0.1 |
VDB | −2.61 | 8 | 0.06 | −0.37 | 0.01 |
Icj | −2.71 | 8 | 0.027 | −0.47 | −0.04 |
VP | −2.70 | 8 | 0.027 | −0.48 | −0.04 |
Tu | −1.95 | 8 | 0.086 | −0.44 | 0.04 |
Parameters | VEH/VEH | VEH/ASE | KET/VEH | KET/ASE |
---|---|---|---|---|
Number of nodes | 32 | 28 | 29 | 32 |
Number of edges | 128 | 34 | 60 | 135 |
Network density | 0.129 | 0.045 | 0.074 | 0.136 |
Characteristic path length | 1.866 | 1.256 | 1.589 | 2.445 |
Connected components | 1 | 4 | 2 | 1 |
Clustering coefficient | 0.328 | 0.193 | 0.255 | 0.332 |
Homer1a Gene Expression Comparison | |||
Treatment Group Differences | ROIs | p-value | |
KET/ASE > KET/VEH | CPDM | ≤0.001 | |
KET/ASE > KET/VEH | CPDL | ≤0.001 | |
KET/ASE > KET/VEH | CPVL | ≤0.001 | |
KET/ASE > KET/VEH | MS | ≤0.001 | |
Comparison of Correlation Matrices | |||
Matrix pairs | ROIs | p-Value | |
VEH/VEH vs. VEH/ASE | M1/GI | ≤0.05 | |
S1j/AIV | ≤0.05 | ||
S1FL/CPDL | ≤0.05 | ||
S1j/CPDL | ≤0.05 | ||
S1FL/CPVL | ≤0.05 | ||
S1j/CPVL | ≤0.05 | ||
S1FL/CI | ≤0.05 | ||
S1j/CI | ≤0.05 | ||
M2/Den | ≤0.05 | ||
S1FL/Den | ≤0.05 | ||
AIV/CPDL | ≤0.05 | ||
AIV/CPVL | ≤0.05 | ||
M1/CPVM | ≤0.05 | ||
S1j/AcSh | ≤0.05 | ||
S1FL/AIV | ≤0.05 | ||
S1FL/LSS | ≤0.05 | ||
M1/CPVL | ≤0.05 | ||
GI/Icj | ≤0.05 | ||
S1j/Den | ≤0.05 | ||
Cg1/CPDL | ≤0.05 | ||
M1/CPDL | ≤0.05 | ||
Cg1/CPVL | ≤0.05 | ||
M2/MS | ≤0.05 | ||
VEH/VEH vs. KET/VEH | M1/AIV | ≤0.05 | |
S1FL/AIV | ≤0.05 | ||
AIV/CPDL | ≤0.05 | ||
Ig/LSI | ≤0.05 | ||
S1j/AIV | ≤0.05 | ||
S1FL/Den | ≤0.05 | ||
S1j/Den | ≤0.05 | ||
AIV/CPVL | ≤0.05 | ||
KET/VEH vs. KET/ASE | Ig/LSI * | ≤0.05 | |
Ig/CPDL * | ≤0.05 | ||
Ig/LSD * | ≤0.05 | ||
Ig/LSV * | ≤0.05 | ||
Ig/S1ULp * | ≤0.05 | ||
Ig/CI * | ≤0.05 | ||
Ig/CPVL * | ≤0.05 | ||
Comparison of Network Measures | |||
Matrix Pairs | Network Measures | p-Value | |
VEH/ASE vs. VEH/VEH | Global Strength | ≤0.05 | |
VEH/VEH vs. VEH/ASE | Node centrality | Cl | ≤0.05 |
CPDL | ≤0.05 | ||
CPDM | ≤0.05 | ||
CPVL | ≤0.05 | ||
S1FL | ≤0.05 | ||
Den | ≤0.05 | ||
Betweenness | Cg2 | ≤0.05 | |
LSV | ≤0.05 | ||
VEH/VEH vs. KET/VEH | Betweenness | M2 | ≤0.05 |
MS | ≤0.05 | ||
KET/VEH vs. KET/ASE | Betweenness | S1DZ | ≤0.01 |
CPDM | ≤0.01 | ||
LSV | ≤0.05 | ||
Ig | ≤0.05 | ||
Shi | ≤0.05 | ||
Pir | ≤0.05 | ||
Cg1 | ≤0.05 |
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Barone, A.; De Simone, G.; Ciccarelli, M.; Buonaguro, E.F.; Tomasetti, C.; Eramo, A.; Vellucci, L.; de Bartolomeis, A. A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration. Int. J. Mol. Sci. 2023, 24, 4372. https://doi.org/10.3390/ijms24054372
Barone A, De Simone G, Ciccarelli M, Buonaguro EF, Tomasetti C, Eramo A, Vellucci L, de Bartolomeis A. A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration. International Journal of Molecular Sciences. 2023; 24(5):4372. https://doi.org/10.3390/ijms24054372
Chicago/Turabian StyleBarone, Annarita, Giuseppe De Simone, Mariateresa Ciccarelli, Elisabetta Filomena Buonaguro, Carmine Tomasetti, Anna Eramo, Licia Vellucci, and Andrea de Bartolomeis. 2023. "A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration" International Journal of Molecular Sciences 24, no. 5: 4372. https://doi.org/10.3390/ijms24054372