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The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis.

Zhu W, Frost EE, Begum F, Vora P, Au K, Gong Y, MacNeil B, Pillai P, Namaka M - J. Cell. Mol. Med. (2012)

Bottom Line: BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi.However, there was no significant change in mRNA levels.The anterograde transport of DRG-derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.

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(A) BDNF immunoreactivity in the dorsal roots. Representative sections of dorsal root entry zones from the lumbar spinal cord of Lewis rats induced to a state of EAE. A marked increase in BDNF immunoreactivity (red) is seen in the dorsal roots of active EAE compared to active control animals and NC animals. Panel i—Naïve animals have no BDNF immunoreactivity in the dorsal roots (DR). Panel ii—Active control animals have noticeable BDNF immunoreactivity in the satellite cells of the DR, and in the grey matter of the dorsal horn. Panel iii—Active EAE animals appear to have increased levels of BDNF immunoreactivity in the satellite cells of the DR, as identified as small brightly stained cell surrounding the axons of the root. In addition, there is a marked increase in punctuate staining in the length of the roots. Further, the grey matter of the dorsal horn has a markedly increased immunoreactivity compared to the active control animals. DR = Dorsal root; SC = spinal cord. Bar = 10 μm. Panel iv—BDNF expression (red) is associated with neurons (labelled with Neuron-specific class III beta-tubulin (Tuj1) – green) in both the DR, and the dorsal horn. Bar = 10 μm (B) Anterograde transport of BDNF along the dorsal root is mediated by kinesin. Double immunolabelling of frozen sections of EAE spinal cord shows BDNF (red) co-localized to the motor protein kinesin (green) (arrow). Kinesin is distributed throughout the dorsal root (DR) and spinal cord (SC). BDNF immunoreactivity is markedly higher in the dorsal root entry zone than the root. Co-labelling shows as yellow. Bar = 10 μm.
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fig05: (A) BDNF immunoreactivity in the dorsal roots. Representative sections of dorsal root entry zones from the lumbar spinal cord of Lewis rats induced to a state of EAE. A marked increase in BDNF immunoreactivity (red) is seen in the dorsal roots of active EAE compared to active control animals and NC animals. Panel i—Naïve animals have no BDNF immunoreactivity in the dorsal roots (DR). Panel ii—Active control animals have noticeable BDNF immunoreactivity in the satellite cells of the DR, and in the grey matter of the dorsal horn. Panel iii—Active EAE animals appear to have increased levels of BDNF immunoreactivity in the satellite cells of the DR, as identified as small brightly stained cell surrounding the axons of the root. In addition, there is a marked increase in punctuate staining in the length of the roots. Further, the grey matter of the dorsal horn has a markedly increased immunoreactivity compared to the active control animals. DR = Dorsal root; SC = spinal cord. Bar = 10 μm. Panel iv—BDNF expression (red) is associated with neurons (labelled with Neuron-specific class III beta-tubulin (Tuj1) – green) in both the DR, and the dorsal horn. Bar = 10 μm (B) Anterograde transport of BDNF along the dorsal root is mediated by kinesin. Double immunolabelling of frozen sections of EAE spinal cord shows BDNF (red) co-localized to the motor protein kinesin (green) (arrow). Kinesin is distributed throughout the dorsal root (DR) and spinal cord (SC). BDNF immunoreactivity is markedly higher in the dorsal root entry zone than the root. Co-labelling shows as yellow. Bar = 10 μm.

Mentions: Based on our model of MS induction [20], we hypothesized that BDNF expression is induced in the DRG and translocated to the dorsal horn along the dorsal roots. To test our hypothesis we assessed the presence of BDNF in the dorsal root in the EAE animals. We show markedly increased BDNF immunoreactivity in the dorsal roots of active EAE animals compared to NC (Fig. 4A). Several previous studies have shown that BDNF is anterogradely transported in vesicles, from the neuronal cell body along the axon to the synapse [27, 28]. Vesicles are moved around in the cell along the cytoskeleton, controlled by motor proteins, the kinesin and dynein protein families [29]. Kinesin has been shown to regulate the anterograde transport of BDNF from the neuronal cell body to the synapse [30, 31]. We demonstrate anterograde transport of BDNF along the dorsal roots, using co-localization of BDNF with the motor protein kinesin [30]. Kinesin-BDNF double immunohistochemistry showed co-localization of the two proteins throughout the dorsal root, and dorsal root entry zone which indicates that BDNF is anterogradely transported to dorsal horn from DRG (Fig. 5B).


The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis.

Zhu W, Frost EE, Begum F, Vora P, Au K, Gong Y, MacNeil B, Pillai P, Namaka M - J. Cell. Mol. Med. (2012)

(A) BDNF immunoreactivity in the dorsal roots. Representative sections of dorsal root entry zones from the lumbar spinal cord of Lewis rats induced to a state of EAE. A marked increase in BDNF immunoreactivity (red) is seen in the dorsal roots of active EAE compared to active control animals and NC animals. Panel i—Naïve animals have no BDNF immunoreactivity in the dorsal roots (DR). Panel ii—Active control animals have noticeable BDNF immunoreactivity in the satellite cells of the DR, and in the grey matter of the dorsal horn. Panel iii—Active EAE animals appear to have increased levels of BDNF immunoreactivity in the satellite cells of the DR, as identified as small brightly stained cell surrounding the axons of the root. In addition, there is a marked increase in punctuate staining in the length of the roots. Further, the grey matter of the dorsal horn has a markedly increased immunoreactivity compared to the active control animals. DR = Dorsal root; SC = spinal cord. Bar = 10 μm. Panel iv—BDNF expression (red) is associated with neurons (labelled with Neuron-specific class III beta-tubulin (Tuj1) – green) in both the DR, and the dorsal horn. Bar = 10 μm (B) Anterograde transport of BDNF along the dorsal root is mediated by kinesin. Double immunolabelling of frozen sections of EAE spinal cord shows BDNF (red) co-localized to the motor protein kinesin (green) (arrow). Kinesin is distributed throughout the dorsal root (DR) and spinal cord (SC). BDNF immunoreactivity is markedly higher in the dorsal root entry zone than the root. Co-labelling shows as yellow. Bar = 10 μm.
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Related In: Results  -  Collection

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fig05: (A) BDNF immunoreactivity in the dorsal roots. Representative sections of dorsal root entry zones from the lumbar spinal cord of Lewis rats induced to a state of EAE. A marked increase in BDNF immunoreactivity (red) is seen in the dorsal roots of active EAE compared to active control animals and NC animals. Panel i—Naïve animals have no BDNF immunoreactivity in the dorsal roots (DR). Panel ii—Active control animals have noticeable BDNF immunoreactivity in the satellite cells of the DR, and in the grey matter of the dorsal horn. Panel iii—Active EAE animals appear to have increased levels of BDNF immunoreactivity in the satellite cells of the DR, as identified as small brightly stained cell surrounding the axons of the root. In addition, there is a marked increase in punctuate staining in the length of the roots. Further, the grey matter of the dorsal horn has a markedly increased immunoreactivity compared to the active control animals. DR = Dorsal root; SC = spinal cord. Bar = 10 μm. Panel iv—BDNF expression (red) is associated with neurons (labelled with Neuron-specific class III beta-tubulin (Tuj1) – green) in both the DR, and the dorsal horn. Bar = 10 μm (B) Anterograde transport of BDNF along the dorsal root is mediated by kinesin. Double immunolabelling of frozen sections of EAE spinal cord shows BDNF (red) co-localized to the motor protein kinesin (green) (arrow). Kinesin is distributed throughout the dorsal root (DR) and spinal cord (SC). BDNF immunoreactivity is markedly higher in the dorsal root entry zone than the root. Co-labelling shows as yellow. Bar = 10 μm.
Mentions: Based on our model of MS induction [20], we hypothesized that BDNF expression is induced in the DRG and translocated to the dorsal horn along the dorsal roots. To test our hypothesis we assessed the presence of BDNF in the dorsal root in the EAE animals. We show markedly increased BDNF immunoreactivity in the dorsal roots of active EAE animals compared to NC (Fig. 4A). Several previous studies have shown that BDNF is anterogradely transported in vesicles, from the neuronal cell body along the axon to the synapse [27, 28]. Vesicles are moved around in the cell along the cytoskeleton, controlled by motor proteins, the kinesin and dynein protein families [29]. Kinesin has been shown to regulate the anterograde transport of BDNF from the neuronal cell body to the synapse [30, 31]. We demonstrate anterograde transport of BDNF along the dorsal roots, using co-localization of BDNF with the motor protein kinesin [30]. Kinesin-BDNF double immunohistochemistry showed co-localization of the two proteins throughout the dorsal root, and dorsal root entry zone which indicates that BDNF is anterogradely transported to dorsal horn from DRG (Fig. 5B).

Bottom Line: BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi.However, there was no significant change in mRNA levels.The anterograde transport of DRG-derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.

Show MeSH
Related in: MedlinePlus