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Glia-related mechanisms in the anteroventral cochlear nucleus of the adult rat in response to unilateral conductive hearing loss.

Fuentes-Santamaría V, Alvarado JC, López-Muñoz DF, Melgar-Rojas P, Gabaldón-Ull MC, Juiz JM - Front Neurosci (2014)

Bottom Line: Diminished cochlear activity after middle ear ossicle removal leads to a significant ipsilateral increase in the mean gray levels and stained area of microglial cells but not astrocytes in the AVCN at 1 and 4 d post-lesion as compared to the contralateral side and control animals.These results suggest that microglial cells but not astrocytes may act as dynamic modulators of synaptic transmission in the cochlear nucleus immediately following unilateral hearing loss.On the other hand, NT-3 immunostaining was localized mainly in neuronal cell bodies and axons and was upregulated at 1, 4 and 7 d post-lesion.

View Article: PubMed Central - PubMed

Affiliation: Facultad de Medicina, Instituto de Investigación en Discapacidades, Neurológicas (IDINE), Universidad de Castilla-La Mancha Albacete, Spain.

ABSTRACT
Conductive hearing loss causes a progressive decline in cochlear activity that may result in functional and structural modifications in auditory neurons. However, whether these activity-dependent changes are accompanied by a glial response involving microglia, astrocytes, or both has not yet been fully elucidated. Accordingly, the present study was designed to determine the involvement of glial related mechanisms in the anteroventral cochlear nucleus (AVCN) of adult rats at 1, 4, 7, and 15 d after removing middle ear ossicles. Quantitative immunohistochemistry analyses at light microscopy with specific markers of microglia or astroglia along with immunocytochemistry at the electron microscopy level were used. Also, in order to test whether trophic support by neurotrophins is modulated in glial cells by auditory activity, the expression and distribution of neurotrophin-3 (NT-3) and its colocalization with microglial or astroglial markers was investigated. Diminished cochlear activity after middle ear ossicle removal leads to a significant ipsilateral increase in the mean gray levels and stained area of microglial cells but not astrocytes in the AVCN at 1 and 4 d post-lesion as compared to the contralateral side and control animals. These results suggest that microglial cells but not astrocytes may act as dynamic modulators of synaptic transmission in the cochlear nucleus immediately following unilateral hearing loss. On the other hand, NT-3 immunostaining was localized mainly in neuronal cell bodies and axons and was upregulated at 1, 4 and 7 d post-lesion. Very few glial cells expressed this neurotrophin in both control and experimental rats, suggesting that NT-3 is primarily activated in neurons and not as much in glia after limiting auditory activity in the AVCN by conductive hearing loss.

No MeSH data available.


Related in: MedlinePlus

Confocal images showing appositions between microglial cells and neurons in the ipsilateral AVCN in control and deprived rats. In control rats, microglial cells with round or fusiform cell bodies and ramified processes were in close proximity to cochlear nucleus neurons (arrows and asterisks in A–C). The frequency of these appositions was particularly increased at 1 and 4 d after the lesion, when enlarged microglial cell bodies with short processes were frequently observed opposing the soma and dendrites of cochlear nucleus neurons in the affected side (arrows and asterisks in D–F). At later survival times after ossicle removal, the occurrence of these cellular contacts decreased (arrows and asterisks in G–L). Scale bar = 25 μm in L.
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Figure 5: Confocal images showing appositions between microglial cells and neurons in the ipsilateral AVCN in control and deprived rats. In control rats, microglial cells with round or fusiform cell bodies and ramified processes were in close proximity to cochlear nucleus neurons (arrows and asterisks in A–C). The frequency of these appositions was particularly increased at 1 and 4 d after the lesion, when enlarged microglial cell bodies with short processes were frequently observed opposing the soma and dendrites of cochlear nucleus neurons in the affected side (arrows and asterisks in D–F). At later survival times after ossicle removal, the occurrence of these cellular contacts decreased (arrows and asterisks in G–L). Scale bar = 25 μm in L.

Mentions: Microglial-neuronal appositions in the ipsilateral AVCN were predominantly observed at 1 and 4 d post-lesion (Figures 5D–F), when microglia assumed a more amoeboid phenotype (arrows in Figure 5E) and surrounded injured cochlear neurons (asterisks in Figure 5D). These close appositions were less frequently seen at day 7 (Figures 5G–I) and were almost absent at day 15 (Figures 5J–L) when microglial cells transformed into the ramified phenotype similar to that seen in the contralateral side and control animals (Figures 5A–C). The utrastructural features of Iba1 immunostained cells in the cochlear nucleus of control and experimental rats are shown in Figure 6. Iba1 immunostained microglial cells were identified by the presence of electron-dense DAB reaction product within their cell body cytoplasm and processes. In the control condition and the side contralateral to the lesion, microglial cells in the resting ramified state had a nucleus with dense heterochromatin packed against the nuclear membrane, a cytoplasm with numerous organelles and inclusion bodies and multiple labeled processes of different sizes and shapes in the neuropil (Shapiro et al., 2009; Figures 6A,B). In the ipsilateral AVCN of experimental animals, activated microglia was characterized by an enlarged cytoplasm and thicker processes rich in vacuoles and multi-vesicular bodies, which were observed surrounding neuronal processes and contacting nearby synaptic elements (Figures 6C,D).


Glia-related mechanisms in the anteroventral cochlear nucleus of the adult rat in response to unilateral conductive hearing loss.

Fuentes-Santamaría V, Alvarado JC, López-Muñoz DF, Melgar-Rojas P, Gabaldón-Ull MC, Juiz JM - Front Neurosci (2014)

Confocal images showing appositions between microglial cells and neurons in the ipsilateral AVCN in control and deprived rats. In control rats, microglial cells with round or fusiform cell bodies and ramified processes were in close proximity to cochlear nucleus neurons (arrows and asterisks in A–C). The frequency of these appositions was particularly increased at 1 and 4 d after the lesion, when enlarged microglial cell bodies with short processes were frequently observed opposing the soma and dendrites of cochlear nucleus neurons in the affected side (arrows and asterisks in D–F). At later survival times after ossicle removal, the occurrence of these cellular contacts decreased (arrows and asterisks in G–L). Scale bar = 25 μm in L.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4195288&req=5

Figure 5: Confocal images showing appositions between microglial cells and neurons in the ipsilateral AVCN in control and deprived rats. In control rats, microglial cells with round or fusiform cell bodies and ramified processes were in close proximity to cochlear nucleus neurons (arrows and asterisks in A–C). The frequency of these appositions was particularly increased at 1 and 4 d after the lesion, when enlarged microglial cell bodies with short processes were frequently observed opposing the soma and dendrites of cochlear nucleus neurons in the affected side (arrows and asterisks in D–F). At later survival times after ossicle removal, the occurrence of these cellular contacts decreased (arrows and asterisks in G–L). Scale bar = 25 μm in L.
Mentions: Microglial-neuronal appositions in the ipsilateral AVCN were predominantly observed at 1 and 4 d post-lesion (Figures 5D–F), when microglia assumed a more amoeboid phenotype (arrows in Figure 5E) and surrounded injured cochlear neurons (asterisks in Figure 5D). These close appositions were less frequently seen at day 7 (Figures 5G–I) and were almost absent at day 15 (Figures 5J–L) when microglial cells transformed into the ramified phenotype similar to that seen in the contralateral side and control animals (Figures 5A–C). The utrastructural features of Iba1 immunostained cells in the cochlear nucleus of control and experimental rats are shown in Figure 6. Iba1 immunostained microglial cells were identified by the presence of electron-dense DAB reaction product within their cell body cytoplasm and processes. In the control condition and the side contralateral to the lesion, microglial cells in the resting ramified state had a nucleus with dense heterochromatin packed against the nuclear membrane, a cytoplasm with numerous organelles and inclusion bodies and multiple labeled processes of different sizes and shapes in the neuropil (Shapiro et al., 2009; Figures 6A,B). In the ipsilateral AVCN of experimental animals, activated microglia was characterized by an enlarged cytoplasm and thicker processes rich in vacuoles and multi-vesicular bodies, which were observed surrounding neuronal processes and contacting nearby synaptic elements (Figures 6C,D).

Bottom Line: Diminished cochlear activity after middle ear ossicle removal leads to a significant ipsilateral increase in the mean gray levels and stained area of microglial cells but not astrocytes in the AVCN at 1 and 4 d post-lesion as compared to the contralateral side and control animals.These results suggest that microglial cells but not astrocytes may act as dynamic modulators of synaptic transmission in the cochlear nucleus immediately following unilateral hearing loss.On the other hand, NT-3 immunostaining was localized mainly in neuronal cell bodies and axons and was upregulated at 1, 4 and 7 d post-lesion.

View Article: PubMed Central - PubMed

Affiliation: Facultad de Medicina, Instituto de Investigación en Discapacidades, Neurológicas (IDINE), Universidad de Castilla-La Mancha Albacete, Spain.

ABSTRACT
Conductive hearing loss causes a progressive decline in cochlear activity that may result in functional and structural modifications in auditory neurons. However, whether these activity-dependent changes are accompanied by a glial response involving microglia, astrocytes, or both has not yet been fully elucidated. Accordingly, the present study was designed to determine the involvement of glial related mechanisms in the anteroventral cochlear nucleus (AVCN) of adult rats at 1, 4, 7, and 15 d after removing middle ear ossicles. Quantitative immunohistochemistry analyses at light microscopy with specific markers of microglia or astroglia along with immunocytochemistry at the electron microscopy level were used. Also, in order to test whether trophic support by neurotrophins is modulated in glial cells by auditory activity, the expression and distribution of neurotrophin-3 (NT-3) and its colocalization with microglial or astroglial markers was investigated. Diminished cochlear activity after middle ear ossicle removal leads to a significant ipsilateral increase in the mean gray levels and stained area of microglial cells but not astrocytes in the AVCN at 1 and 4 d post-lesion as compared to the contralateral side and control animals. These results suggest that microglial cells but not astrocytes may act as dynamic modulators of synaptic transmission in the cochlear nucleus immediately following unilateral hearing loss. On the other hand, NT-3 immunostaining was localized mainly in neuronal cell bodies and axons and was upregulated at 1, 4 and 7 d post-lesion. Very few glial cells expressed this neurotrophin in both control and experimental rats, suggesting that NT-3 is primarily activated in neurons and not as much in glia after limiting auditory activity in the AVCN by conductive hearing loss.

No MeSH data available.


Related in: MedlinePlus