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| Status |
Public on Mar 31, 2018 |
| Title |
Comprehensive analysis of area-specific and time-dependent changes in gene expression in the motor cortex of macaque monkeys during recovery from spinal cord injury |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by array
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| Summary |
The present study aimed to assess the molecular bases of cortical compensatory mechanisms following spinal cord injury in primates. To accomplish this, comprehensive changes in gene expression were investigated in the bilateral primary motor cortex (M1), dorsal premotor cortex (PMd), and ventral premotor cortex (PMv) after a unilateral lesion of the lateral corticospinal tract (l-CST). At 2 weeks after the lesion, a large number of genes exhibited altered expression levels in the contralesional M1, which is directly linked to the lesioned l-CST. Gene ontology and network analyses indicated that these changes in gene expression are involved in the atrophy and plasticity changes observed in neurons. Orchestrated gene expression changes were present when behavioral recovery was attained 3 months after the lesion, particularly among the bilateral premotor areas, and a large number of these genes are involved in plasticity. Moreover, several genes abundantly expressed in M1 of intact monkeys were upregulated in both the PMd and PMv after the l-CST lesion. These area-specific and time-dependent changes in gene expression may underlie the molecular mechanisms of functional recovery following a lesion of the l-CST.
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| Overall design |
Brain tissue samples were obtained from 9 young adolescent rhesus monkeys (Macaca mulatta), 3-4 years old, and categorized into the following groups: intact monkeys (n = 3), monkeys perfused at 2 weeks after lesioning of the l-CST (n = 3), and monkeys perfused at 3 months (n = 3) after lesioning of the l-CST. The animal use protocol was approved by the National Institutes of Natural Sciences, and adequate measures were taken to minimize any pain and discomfort in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH publication no. 80?23). The l-CST lesion was established as described previously (Sasaki S et al. 2004; Nishimura Y et al. 2007). First, the animals were anesthetized using ketamine hydrochloride (10 mg/kg, intramuscular [i.m.]) and xylazine (1 mg/kg, i.m.), and anesthesia was maintained using sodium pentobarbital (20 mg/kg, intravenous [i.v.]). The border between the C4 and C5 spinal segments was exposed by laminectomy of the C3 and C4 vertebrae, and a transverse opening was made in the dura. The l-CST lesion was made under a surgical microscope in three steps. First, a small opening was made in the pia mater at the lateral convexity of the spinal cord, and a horizontal strip was made in a mediolateral direction relative to the lateral funiculus by inserting a minute L-shape hook that could not be inserted more than 5 mm deep, which corresponds to the distance from the lateral convexity of the spinal cord to the midline. Second, using watchmaker's forceps, the dorsal part of the lateral funiculus was ventrally transected from the dorsal root entry zone to the level of the horizontal strip lesioned in Step 1. Third, the lesion was extended ventrally using the watchmaker?s forceps at the most lateral part of the lateral funiculus. Finally, the opening of the dura mater was closed, and the skin and back muscles were sutured using either nylon or silk.
Hand movement performances prior to and after the lesion were evaluated daily using a small-object retrieval task in which the monkeys had to reach, grasp, and retrieve a small piece of sweet potato (7 × 7 × 7 mm in size) through a narrow vertical slit using their index finger and thumb. The food piece was placed at the center of the vertical slit, which was at shoulder height for each monkey at a sagittal distance of 15 cm. The monkeys were trained intensively every day to retrieve these small food pieces, sometimes using manual assistance of the movements, as described previously (Sugiyama Y et al. 2013).
Following the completion of the behavioral tests, the monkeys were perfused with 500-1000 ml ice cold saline containing heparin sodium (1000 units/ml, Novo Heparin, Leo Pharmaceutical Products; Ballerup, Denmark) through the ascending aorta within 15 min of an overdose injection of pentobarbital sodium (50 mg/kg, intraperitoneal [i.p.], Somnopentyl, Kyoritsu Shoji; Tokyo, Japan). The abovementioned six neocortical areas (bilateral M1, PMd, and PMv) were determined using sulcal landmarks. A total of 50?150 mg of tissue from each area was dissected and frozen immediately in liquid nitrogen. The forelimb region of M1, which is located around the superior genu of the central sulcus (Higo N et al. 2007; Murata Y et al. 2015), was obtained for the present analysis. The PMd and PMv were obtained from the caudal bank of the upper and lower limbs of the arcuate sulcus and their convex regions rostral to M1, respectively.
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| Contributor(s) |
Kojima T, Higo N, Sato A, Yamamoto T, Oishi T, Nishimura Y, Murata Y, Onoe H, Isa T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
May 10, 2016 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Toshio Kojima |
| Organization name |
Toyohashi University of Technology
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| Department |
Health Care Center
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| Street address |
1-1 Hibarigaoka Tenpaku-cho
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| City |
Toyohashi |
| ZIP/Postal code |
441-8580 |
| Country |
Japan |
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| Platforms (1) |
| GPL14569 |
Agilent-015421 Rhesus Macaque Gene Expression Microarray (Probe Name Version) |
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| Samples (54)
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| Relations |
| BioProject |
PRJNA321132 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE81264_RAW.tar |
94.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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