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Paclitaxel causes degeneration of both central and peripheral axon branches of dorsal root ganglia in mice.

Tasnim A, Rammelkamp Z, Slusher AB, Wozniak K, Slusher BS, Farah MH - BMC Neurosci (2016)

Bottom Line: Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies.In the peripheral nerves, degenerated myelinated fibers were present in significantly greater numbers in distal segments than in proximal segments indicating that this model exhibits the distal-to-proximal degeneration pattern generally observed in human peripheral nerve disorders.We conclude that paclitaxel causes degeneration of both the peripheral and central branches of DRG axons, a finding that has implications for the site and mode of action of chemotherapy agents on the nervous system.

View Article: PubMed Central - PubMed

Affiliation: Neuromuscular Division, Department of Neurology, Johns Hopkins University School of Medicine, The John G. Rangos Sr. Building, Room 239, 855 N. Wolfe Street, Baltimore, MD, 21205, USA.

ABSTRACT

Background: Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies. The taxane agents, including paclitaxel (Taxol(®)), are effective chemotherapeutic drugs but cause degeneration of predominantly large myelinated afferent sensory fibers of the peripheral nervous system in humans and animal models. Dorsal root ganglia (DRG) neurons are sensory neurons that have unipolar axons each with two branches: peripheral and central. While taxane agents induce degeneration of peripheral axons, whether they also cause degeneration of central nervous system axons is not clear. Using a mouse model of paclitaxel-induced neuropathy, we investigated the effects of paclitaxel on the central branches of sensory axons.

Results: We observed that in the spinal cords of paclitaxel-intoxicated mice, degenerated axons were present in the dorsal columns, where the central branches of DRG axons ascend rostrally. In the peripheral nerves, degenerated myelinated fibers were present in significantly greater numbers in distal segments than in proximal segments indicating that this model exhibits the distal-to-proximal degeneration pattern generally observed in human peripheral nerve disorders.

Conclusions: We conclude that paclitaxel causes degeneration of both the peripheral and central branches of DRG axons, a finding that has implications for the site and mode of action of chemotherapy agents on the nervous system.

No MeSH data available.


Related in: MedlinePlus

DRG cell bodies after paclitaxel intoxication. a Control DRG. b Paclitaxel intoxicated DRG. Minor alternations are seen such as small nucleoli in the large neurons of the paclitaxel-treated mice. Scale bar in b = 10 μm and applies to a, b
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Fig5: DRG cell bodies after paclitaxel intoxication. a Control DRG. b Paclitaxel intoxicated DRG. Minor alternations are seen such as small nucleoli in the large neurons of the paclitaxel-treated mice. Scale bar in b = 10 μm and applies to a, b

Mentions: We next examined DRG for signs of neuronal cell body degeneration. We did not observe massive degeneration of neuronal cell bodies (Fig. 5), nor did we observe pyknotic nuclei or fragmented neuronal cells. Instead, we observed minor alterations such as small nucleoli in the large neurons of the paclitaxel-treated mice, supporting the notion that the predominant adverse action of paclitaxel is likely to be on axons, though we cannot exclude contributions from alterations in DRG.Fig. 5


Paclitaxel causes degeneration of both central and peripheral axon branches of dorsal root ganglia in mice.

Tasnim A, Rammelkamp Z, Slusher AB, Wozniak K, Slusher BS, Farah MH - BMC Neurosci (2016)

DRG cell bodies after paclitaxel intoxication. a Control DRG. b Paclitaxel intoxicated DRG. Minor alternations are seen such as small nucleoli in the large neurons of the paclitaxel-treated mice. Scale bar in b = 10 μm and applies to a, b
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4940970&req=5

Fig5: DRG cell bodies after paclitaxel intoxication. a Control DRG. b Paclitaxel intoxicated DRG. Minor alternations are seen such as small nucleoli in the large neurons of the paclitaxel-treated mice. Scale bar in b = 10 μm and applies to a, b
Mentions: We next examined DRG for signs of neuronal cell body degeneration. We did not observe massive degeneration of neuronal cell bodies (Fig. 5), nor did we observe pyknotic nuclei or fragmented neuronal cells. Instead, we observed minor alterations such as small nucleoli in the large neurons of the paclitaxel-treated mice, supporting the notion that the predominant adverse action of paclitaxel is likely to be on axons, though we cannot exclude contributions from alterations in DRG.Fig. 5

Bottom Line: Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies.In the peripheral nerves, degenerated myelinated fibers were present in significantly greater numbers in distal segments than in proximal segments indicating that this model exhibits the distal-to-proximal degeneration pattern generally observed in human peripheral nerve disorders.We conclude that paclitaxel causes degeneration of both the peripheral and central branches of DRG axons, a finding that has implications for the site and mode of action of chemotherapy agents on the nervous system.

View Article: PubMed Central - PubMed

Affiliation: Neuromuscular Division, Department of Neurology, Johns Hopkins University School of Medicine, The John G. Rangos Sr. Building, Room 239, 855 N. Wolfe Street, Baltimore, MD, 21205, USA.

ABSTRACT

Background: Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies. The taxane agents, including paclitaxel (Taxol(®)), are effective chemotherapeutic drugs but cause degeneration of predominantly large myelinated afferent sensory fibers of the peripheral nervous system in humans and animal models. Dorsal root ganglia (DRG) neurons are sensory neurons that have unipolar axons each with two branches: peripheral and central. While taxane agents induce degeneration of peripheral axons, whether they also cause degeneration of central nervous system axons is not clear. Using a mouse model of paclitaxel-induced neuropathy, we investigated the effects of paclitaxel on the central branches of sensory axons.

Results: We observed that in the spinal cords of paclitaxel-intoxicated mice, degenerated axons were present in the dorsal columns, where the central branches of DRG axons ascend rostrally. In the peripheral nerves, degenerated myelinated fibers were present in significantly greater numbers in distal segments than in proximal segments indicating that this model exhibits the distal-to-proximal degeneration pattern generally observed in human peripheral nerve disorders.

Conclusions: We conclude that paclitaxel causes degeneration of both the peripheral and central branches of DRG axons, a finding that has implications for the site and mode of action of chemotherapy agents on the nervous system.

No MeSH data available.


Related in: MedlinePlus