Effects of Prolonged Treatment With the Opiate Tramadol on Prodynorphin Gene Expression in Rat CNS

Abstract

In addition to its traditional role in reproduction, progesterone (PROG) has demonstrated neuroprotective and promyelinating effects in lesions of the peripheral and central nervous systems, including the spinal cord. The latter is a target of PROG, as nuclear receptors, as well as membrane receptors, are expressed by neurons and/or glial cells. When spinal cord injury (SCI) is produced at the thoracic level, several genes become sensitive to PROG in the region caudal to the lesion site. Although the cellular machinery implicated in PROG neuroprotection is only emerging, neurotrophins, their receptors, and signaling cascades might be part of the molecules involved in this process. In rats with SCI, a 3-d course of PROG treatment increased the mRNA of brain-derived neurotrophic factor (BDNF) and BDNF immunoreactivity in perikaryon and processes of motoneurons, whereas chromatolysis was strongly prevented. The increased expression of BDNF correlated with increased immunoreactivity for the BDNF receptor TrkB and for phosphorylated cAMP-responsive element binding in motoneurons. In the same SCI model, PROG restored myelination, according to measurements of myelin basic protein (MBP) and mRNA levels, and further increased the density of NG2+-positive oligodendrocyte progenitors. These cells might be involved in remyelination of the lesioned spinal cord. Interestingly, similarities in the regulation of molecular parameters and some cellular events attributed to PROG and BDNF (i.e., choline acetyltransferase, Na,K-ATPase, MBP, chromatolysis) suggest that BDNF and PROG might share intracellular pathways. Furthermore, PROG-induced BDNF might regulate, in a paracrine or autocrine fashion, the function of neurons and glial cells and prevent the generation of damage.

Reward Processing by the Opioid System in the Brain

“…Repeated morphine exposure decreased Pdyn or Dyn expression in the CPu and NAc in several studies (56, 130, 302, 372). An upregulation in these two regions (375) or no change (406) was also reported.…”

“…An upregulation in these two regions (375) or no change (406) was also reported. Decreased Pdyn mRNA levels were observed in the HPC (56) and HPT (26, 56). Chronic treatment with kappa receptor agonists (U-69593 or U-50,488H) consistently decreased levels of Pdyn mRNA in the CPu, HPC, and FrCx (70, 321).…”

Longitudinal Neuroimaging in Pediatric Traumatic Brain Injury: Current State and Consideration of Factors That Influence Recovery

“…Increased levels of progesterone have been shown to reduce brain edema, increase neuronal survival, and impact the expression of genes involved in the regulation of inflammatory responses and apoptosis in brain injured rats (83,84). Progesterone has also been implicated as a promotor of axon regeneration and remyelination (85,86), and this is supported by research demonstrating sex differences in neuroplasticity following early brain injury to rats (87).…”

Recent advances in the pharmacologic treatment of spinal cord injury

“…Results of a study conducted in a rat SCI model indicated that treatment with progesterone resulted in sparing of white matter tissue with concomitant improvement in motor function (Thomas et al 1999). A mechanistic study examining the effects of progesterone in a rat model of SCI reported that progesterone treatment restored myelin levels and increased the density of oligodendrocyte progenitor cells, potentially responsible for remyelination (De Nicola et al 2006). An additional study reported that progesterone may be working by suppressing gliosis at the early stage of SCI while promoting oligodendrocyte differentiation and remyelination at the later stages (Labombarda et al 2011).…”