Differential roles of hippocampal glutamatergic receptors in neuropathic anxiety-like behavior after partial sciatic nerve ligation in rats.

BACKGROUND: Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions. RESULTS: We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL. CONCLUSIONS: PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury.

Fas and FasL expression in the spinal cord following cord hemisection in the monkey.

The changes of endogenous Fas/FasL in injured spinal cord, mostly in primates, are not well known. In this study, we investigated the temporal changes in the expression of Fas and FasL and explored their possible roles in the ventral horn of the spinal cord and associated precentral gyrus following T(11) spinal cord hemisection in the adult rhesus monkey. A significant functional improvement was seen with the time going on in monkeys subjected to cord hemisection. Apoptotic cells were also seen in the ventral horn of injured spinal cord with TUNEL staining, and a marked increase presents at 7 days post operation (dpo). Simultaneously, the number of Fas and FasL immunoreactive neurons in the spinal cords caudal and rostral to injury site and their intracellular optical density (OD) in the ipsilateral side of injury site at 7 dpo increased significantly more than that of control group and contralateral sides. This was followed by a decrease and returned to normal level at 60 dpo. No positive neurons were observed in precentral gyrus. The present results may provide some insights to understand the role of Fas/FasL in the spinal cord but not motor cortex with neuronal apoptosis and neuroplasticity in monkeys subjected to hemisection spinal cord injury.