Changes in GABAA receptor subunit gamma 2 in extensor and flexor motoneurons and astrocytes after spinal cord transection and motor training

• Published in: Brain research Vol. 1273; pp. 9 - 17
• Main Authors: Khristy, Windyanne, Ali, Noore J, Bravo, Arlene B, de Leon, Ray, Roy, Roland R, Zhong, Hui, London, Nik J.L, Edgerton, V. Reggie, Tillakaratne, Niranjala J.K
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.06.2009
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Neurology; Vertebrates: nervous system and sense organs; Immunohistochemistry; FG; Fluoro Gold; GABA A receptor; tibialis anterior; Spinal cord transection; FITC; DMCM; fibroblast growth factor 2; Fast Blue; fluorescein isothiocyanate; Motoneuron; GAD; Astrocyte; gamma aminobutyric acid; ROI; TA; GFAP; glutamic acid decarboxylase; FGF-2; γ; region of interest; GABA; methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; FB; glial fibrillary acidic protein; Step training; gamma; Physical exercise; Spinal cord; Physical training; Rat; Neuroglia; Rodentia; Central nervous system; Motor neuron; Subunit; Vertebrata; Mammalia; receptor; Animal; Gabaergic receptor A
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.03.060

Abstract 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 γ2 subunit of the GABAA receptor is necessary for benzodiazepine binding, this subunit may be an important factor modulating sensorimotor function after an injury. Changes in γ2 levels in muscle-specific motoneurons and surrounding astrocytes were determined ∼ 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 γ2 immunostaining in both soleus and TA motoneurons and astrocytes. γ2 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 γ2 in TA, and lower levels in soleus motoneurons. Step training restored GABAA γ2 levels towards control values in motoneuronal pools of both muscles. In contrast, the γ2 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 γ2 subunit is involved with GABAA 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.