Background
Methods
Ethics statement
Postmortem samples
Variable | Control | ASD |
---|---|---|
Age (years) | 11.70 ± 1.584 | 11.80 ± 1.609 |
PMI (h) | 14.46 ± 2.171 | 19.00 ± 2.776 |
Gender (F/M) | 1/12 | 0/13 |
Storage (days) | 4,287 ± 638.7 | 2,829 ± 397.7 |
RIN | 5.55 ± 0.71 | 6.84 ± 0.53 |
pH | 5.95 ± 0.06 | 6.11 ± 0.07 |
Primary cortical neurons
Immunoblotting
Quantitative reverse transcriptase PCR (qRT-PCR)
Small interfering RNA (siRNA)
Human Ubiquitination Pathway PCR Array
Proteasome activity assay
Immunofluorescence
Statistical analyses
Results
Decrease in GABAAα1 protein, but not mRNA levels in the middle frontal gyrus of ASD subjects
GABAAα1 mRNA | GABAAα1 protein | |||||||
---|---|---|---|---|---|---|---|---|
CON | ASD | CON | ASD | |||||
r |
P
| r |
P
| r |
P
| r |
P
| |
Age | -0.260 | 0.414 | -0.329 | 0.296 | -0.960 | 0.542 | 0.044 | 0.891 |
PMI | 0.014 | 0.967 | -0.071 | 0.826 | -0.110 | 0.734 | 0.148 | 0.647 |
Storage | -0.456 | 0.136 | -0.162 | 0.614 | -0.229 | 0.474 | -0.126 | 0.695 |
RIN | 0.202 | 0.528 | 0.109 | 0.736 | -0.190 | 0.553 | 0.451 | 0.125 |
pH | 0.236 | 0.460 | -0.312 | 0.324 | -0.349 | 0.266 | 0.445 | 0.148 |
Social interaction | 0.253 | 0.546 | 0.407 | 0.316 | ||||
Verbal communication | 0.496 | 0.395 | -0.643 | 0.169 | ||||
Non-verbal communication | -0.067 | 0.887 | -0.625 | 0.134 | ||||
Stereotyped behavior | -0.595 | 0.119 | 0.598 | 0.117 | ||||
Abnormality of development | -0.081 | 0.848 | 0.294 | 0.522 |
GABAAα1 levels are regulated through ubiquitin-proteasomal degradation
Ubiquitination pathway is altered in the middle frontal gyrus of ASD subjects
CON | ASD | |||
---|---|---|---|---|
r |
P
| r |
P
| |
Age | -0.516 | 0.071 | -0.510 | 0.075 |
PMI | 0.253 | 0.405 | 0.271 | 0.371 |
Storage | -0.163 | 0.593 | 0.227 | 0.455 |
RIN | 0.240 | 0.430 | 0.412 | 0.173 |
pH | 0.044 | 0.887 | 0.437 | 0.135 |
Social interaction | 0.189 | 0.626 | ||
Verbal communication | -0.580 | 0.228 | ||
Non-verbal communication | -0.712 | 0.047* | ||
Stereotyped behavior | 0.509 | 0.162 | ||
Abnormality of development | -0.319 | 0.441 |