Increased expression of the growth‐associated protein 43 gene in the sensorimotor cortex of the macaque monkey after lesioning the lateral corticospinal tract

Abstract

To investigate the neural basis for functional recovery of the cerebral cortex following spinal cord injury, we measured the expression of growth-associated protein 43 (GAP-43), which is involved in the process of synaptic sprouting. We determined the GAP-43 mRNA expression levels in the sensorimotor cortical areas of macaque monkeys with a unilateral lesion of the lateral corticospinal tract (l-CST) at the C4/C5 level of the cervical cord and compared them with the levels in the corresponding regions of intact monkeys. Lesioned monkeys recovered finger dexterity during the first months after surgery, and the GAP-43 mRNA levels increased in layers II-III in primary motor areas (M1), bilaterally. Double-labeling analysis of the lesioned monkeys showed that GAP-43 mRNA was expressed strongly in excitatory neurons but only rarely in inhibitory interneurons. Expression also increased in the medium-sized (area, 500-1,000 microm(2)) and large pyramidal cells (area, >1,000 microm(2)) in layer V of the bilateral M1. The increased expression of GAP-43 mRNA in the M1 contralateral to the lesion was more prominent during the early recovery stage than during the late recovery stage. In addition, GAP-43 mRNA increased in layers II-III of both the contralesional ventral premotor area and the primary somatosensory area. These results suggest that GAP-43 is involved in time-dependent and brain region-specific plastic changes after l-CST lesioning. The expression patterns imply that plastic changes occur not only in M1 but also in the broad associative cortical network, including the ventral premotor and primary sensory areas.

Contribution of propriospinal neurons to recovery of hand dexterity after corticospinal tract lesions in monkeys

“…4C), despite the intensive rehabilitative training required during the early period after the lesion (29). These findings contrasted obviously with those of previous studies, in which dexterous hand movements of all monkeys with C4-C5 CST lesions of this size largely recovered within 1-3 mo (15,17,21,28). These findings suggested that the PNs played a key role in promoting the recovery of dexterous hand movements after the CST lesion.…”

“…The extent of CST lesions in these two monkeys (K and R in Fig. 1B; 61.5% and 54.5%, respectively; Table S1) was not larger than those in previous studies (15,17,21,28), which would lead us to expect near complete recovery. However, in these two monkeys, alternate grip strategies, which indicate insufficient recovery (41), persisted throughout the entire period of observation.…”

“…The dorsolateral funiculus was lesioned unilaterally at the C4-C5 segment to completely interrupt the direct CM transmission (15,17,19,21,28,29), while sparing the axons of the PNs and RSNs. In the present study, five of the six monkeys had a lesion in C4-C5 (monkeys U, B, S, K, and R), whereas the lesion of monkey N was located in C6/C7 (Fig.…”

Epigenetics and Biomarkers in the Staging of Neuropsychiatric Disorders

“…Gene expressions of DA and GABA in the neonatal ventral hippocampal-lesioned animal model and the interactions of antipsychotic agents provide a degree of plausibility for the notion of endophenotypic expression of the biomarkers involving the disorder model in its ramifications (Pezzi et al 2005;Lodge and Grace 2007;Mouri et al 2007;Stone et al 2007;Tseng et al 2007;François et al 2009). Despite this and the glut of primate and rodent methods that model positive, negative, and cognitive symptoms of schizophrenia spectrum disorders (Barkus et al 2009;Bertrand et al 2010;Bickel and Javitt 2009), symptom-profile similarity and therapeutic affirmations remain bedeviled in the face of epigenetic configurations at the basis of an eventual staging (Higo et al 2009). …”

Histological and electrophysiological analysis of the corticospinal pathway to forelimb motoneurons in common marmosets

“…Recent studies suggested that expression of secreted phosphoprotein 1 (SPP1) mRNA in the motor cortex is correlated with the existence of direct CM connection (Higo et al, 2009;Yamamoto et al, 2013). SPP1 mRNA is expressed in layer V neurons in the sensorimotor cortex of rhesus macaques, Cebus monkeys, and humans but only weakly or not expressed in squirrel monkeys, marmosets, and rats.…”