Changes in GABA(A) receptor subunit gamma 2 in extensor and flexor motoneurons and astrocytes after spinal cord transection and motor training.
GABA signaling plays an important role in the spinal cord response to injury and subsequent motor training. Since benzodiazepines are commonly used to treat muscle spasticity in spinal cord injured subjects and the gamma2 subunit of the GABA(A) receptor is necessary for benzodiazepine binding, this subunit may be an important factor modulating sensorimotor function after an injury. Changes in gamma2 levels in muscle-specific motoneurons and surrounding astrocytes were determined approximately 3 months after a complete mid-thoracic spinal cord transection at P5 in non-trained and in step-trained spinal rats. Soleus (ankle extensor) and tibialis anterior (TA, ankle flexor) motor pools were identified using retrograde labeling via intramuscular injections of Fast Blue or Fluoro Gold, respectively. Lumbar spinal cord sections showed gamma2 immunostaining in both soleus and TA motoneurons and astrocytes. gamma2 immunoreactivity on the soma of soleus and TA motoneurons in spinal rats was differentially modulated. Compared to intact rats, spinal rats had higher levels of gamma2 in TA, and lower levels in soleus motoneurons. Step training restored GABA(A) gamma2 levels towards control values in motoneuronal pools of both muscles. In contrast, the gamma2 levels were elevated in surrounding astrocytes of both motor pools in spinal rats, and step training had no further effect. Thus, motor training had a specific effect on those neurons that were directly involved with the motor task. Since the gamma2 subunit is involved with GABA(A) receptor trafficking and synaptic clustering, it appears that this subunit could be an important component of the activity-dependent response of the spinal cord after a spinal injury.
Department of Physiological Science, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Windyanne
W
Khristy
Noore J
NJ
Ali
Arlene B
AB
Bravo
Ray
R
de Leon
Roland R
RR
Roy
Hui
H
Zhong
Nik J L
NJ
London
V Reggie
VR
Edgerton
Niranjala J K
NJ
Tillakaratne
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation; D009473:Neuronal Plasticity / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology / Q000534:rehabilitation*; D013194:Staining and Labeling; D015854:Up-Regulation / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005456:Fluorescent Dyes; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid