Expression of p-Akt in sensory neurons and spinal cord after peripheral nerve injury.

Akt has been implicated in pro-survival and anti-apoptotic activities in many cell types, including dorsal root ganglion (DRG) and spinal motor neurons. In this immunohistochemical study we have monitored phosphorylated Akt (p-Akt) levels in adult mouse DRGs and spinal cord following unilateral peripheral sciatic nerve transection (axotomy) or carrageenan-induced inflammation. In control animals around half of the lumbar DRG neuron profiles (NPs), mainly small and medium-sized ones, were p-Akt immunoreactive (IR), and of these around 50% expressed calcitonin gene-related peptide and/or isolectin IB4. Two weeks after axotomy, the number of p-Akt-positive NPs was only slightly reduced, but p-Akt immunofluorescence intensity was strongly increased. One third of the ipsilateral p-Akt-IR NPs was galanin positive, but virtually without colocalization with neuropeptide Y. Furthermore, p-Akt-like immunoreactivity significantly increased in intensity in the ipsilateral spinal dorsal horn after axotomy and expanded into deeper layers. Carrageenan-induced peripheral inflammation increased the number of p-Akt-IR NPs after 1 h. Both axotomy and inflammation caused a clear increase in nuclear p-Akt-like immunoreactivity in DRG neurons. Our findings support a role for Akt as a key signaling molecule in sensory neurons and spinal cord after peripheral injury.

Shi TJ ，Huang P ，Mulder J ，Ceccatelli S ，Hokfelt T ... -  《-》

Phenotyping of sensory and sympathetic ganglion neurons of a galanin-overexpressing mouse--possible implications for pain processing.

Brumovsky P ，Hygge-Blakeman K ，Villar MJ ，Watanabe M ，Wiesenfeld-Hallin Z ，Hökfelt T ... -  《JOURNAL OF CHEMICAL NEUROANATOMY》

Differential galanin upregulation in dorsal root ganglia and spinal cord after graded single ligature nerve constriction of the rat sciatic nerve.

Coronel MF ，Brumovsky PR ，Hökfelt T ，Villar MJ ... -  《JOURNAL OF CHEMICAL NEUROANATOMY》

Deletion of the neuropeptide Y Y1 receptor affects pain sensitivity, neuropeptide transport and expression, and dorsal root ganglion neuron numbers.

Shi TJ ，Li J ，Dahlström A ，Theodorsson E ，Ceccatelli S ，Decosterd I ，Pedrazzini T ，Hökfelt T ... -  《NEUROSCIENCE》

Effect of axotomy on expression of NPY, galanin, and NPY Y1 and Y2 receptors in dorsal root ganglia and the superior cervical ganglion studied with double-labeling in situ hybridization and immunohistochemistry.

Using double-labeling techniques for both in situ hybridization and immunohistochemistry some peptides and peptide receptors were studied quantitatively in a sensory and a sympathetic ganglion after axotomy. In the lumbar 5 dorsal root ganglion (DRG) normally no neuropeptide Y- and only a few galanin-positive cell bodies are seen. Following complete transection of the sciatic nerve around 60% of all neuropeptide Y (NPY) neuron profiles (NPs) were galanin positive (+) and 33-44% of all galanin NPs were NPY(+). A good agreement between immunohistochemistry and in situ hybridization was observed for NPY and galanin. NPY Y1- and Y2-receptor (R) mRNAs were found in around 40% of all NPY mRNA(+) NPs, and more than half of the Y1-R mRNA(+) NPs and two-thirds of the Y2-R mRNA(+) NPs were NPY(+). In addition, more than one-third of the galanin mRNA-containing NPs showed colocalization with NPY receptor mRNAs and up to 70% of the Y2-R mRNA(+) NPs also expressed galanin mRNA. In the control superior cervical ganglion (SCG) 10% of the NPY(+) NPs were Y2-R mRNA(+), and 85% of the Y2-R(+) NPs were NPY mRNA(+), and the corresponding percentages after axotomy were around 35 and 45%, respectively. Following axotomy of the carotid nerves around half of all NPY(+) NPs were galanin(+), and conversely around 50% of all galanin NPs were NPY(+) at the mRNA level, whereas much lower percentages (15 and 9%, respectively) were observed with immunohistochemistry. These results demonstrate that double-labeling procedures are valid tools to quantitatively evaluate coexistence situations in sensory and sympathetic ganglia, showing a high degree of coexistence for NPY and galanin in axotomized neurons both in the lumbar 5 DRG and in the SCG. However, the immunohistochemical analysis in the SCG demonstrated much lower numbers of peptide-positive neurons than seen with in situ hybridization, suggesting that the latter technique is more sensitive. The fact that a considerable number of neurons express NPY together with Y1- and/or Y2-Rs indicates that both receptors may act as autoreceptors, the Y1-R presumably at the level of the cell body and the Y2-R on nerve terminals in the dorsal horn and/or the periphery. The present results also show that in both sensory and sympathetic neurons there is a strong upregulation of the Y2-R after nerve injury, suggesting a possible role in trophic and regenerative events.

Landry M ，Holmberg K ，Zhang X ，Hökfelt T ... -  《EXPERIMENTAL NEUROLOGY》