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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

Images depicting Iba1 immunostaining in the AVCN in control and experimental animals. In the ipsilateral side, Iba1 immunostaining increased at 1d post-lesion (arrows in C) and peaked around 4d (arrows in D) in comparison with the contralateral side and unoperated animals (arrows in A,B). Iba1 levels remained elevated at 7d (arrows in E) and decreased at 15d (arrows in F) post-lesion. The morphological features of these cells are shown in G–K. Particularly at 7d post-lesion, activated microglial cells assumed very diverse phenotypes (compare asterisk and arrows in E). The inset in A indicates the location of the AVCN, and the square box indicates the approximate locations of the fields represented in A–F. Scale bar = 250 μm in A; 50 μm in F; 10 μm in K.
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Figure 3: Images depicting Iba1 immunostaining in the AVCN in control and experimental animals. In the ipsilateral side, Iba1 immunostaining increased at 1d post-lesion (arrows in C) and peaked around 4d (arrows in D) in comparison with the contralateral side and unoperated animals (arrows in A,B). Iba1 levels remained elevated at 7d (arrows in E) and decreased at 15d (arrows in F) post-lesion. The morphological features of these cells are shown in G–K. Particularly at 7d post-lesion, activated microglial cells assumed very diverse phenotypes (compare asterisk and arrows in E). The inset in A indicates the location of the AVCN, and the square box indicates the approximate locations of the fields represented in A–F. Scale bar = 250 μm in A; 50 μm in F; 10 μm in K.

Mentions: In the control condition and in the side contralateral to the lesion, microglial cells in the AVCN had round or oval cell bodies and long ramified processes (Figures 3A,B,G). A microglial reaction in the ipsilateral AVCN of experimental animals was first detectable 1 day after the lesion, at which time glial cells had larger cell bodies along with thicker and less branched processes than resting microglia (Figures 3C,H). At 4d post-lesion, microglial expression was maximal (Figures 3D,I) when compared to that in the intact side (Figure 3B) and control (Figure 3A) animals. Cells were larger, darker and occupied a larger area when compared to those observed at 1d post-lesion. These qualitative observations were confirmed by significant increases in their cross-sectional area, mean gray level of Iba1 immunostaining and immunostained area (Figure 4; Table 2). At 7d post-lesion, glial cells displayed a remarkable heterogeneity in their morphology. Some cells had smaller cell bodies and longer processes (arrowheads in Figures 3E,J) while others had morphologies resembling those seen at 1 and 4 d post-lesion (compare asterisk and arrows in Figure 3E). At this time point, the microglial cross-sectional area was significantly decreased when compared with the other survival time points. However, it was increased when compared with the unmanipulated side and control animals (Figures 3, 4; Table 2). Glial cells were still darkly immunostained as confirmed by significant decreases in the mean gray levels when compared with experimental animals at 4d post-lesion, but no differences were found when compared with 1d post-lesion animals (Figure 4; Table 2). At longer survival times (15d post-lesion), microglial cells adopted the typical ramified structure usually seen in the normal brain (Figures 3F,K, 4).


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)

Images depicting Iba1 immunostaining in the AVCN in control and experimental animals. In the ipsilateral side, Iba1 immunostaining increased at 1d post-lesion (arrows in C) and peaked around 4d (arrows in D) in comparison with the contralateral side and unoperated animals (arrows in A,B). Iba1 levels remained elevated at 7d (arrows in E) and decreased at 15d (arrows in F) post-lesion. The morphological features of these cells are shown in G–K. Particularly at 7d post-lesion, activated microglial cells assumed very diverse phenotypes (compare asterisk and arrows in E). The inset in A indicates the location of the AVCN, and the square box indicates the approximate locations of the fields represented in A–F. Scale bar = 250 μm in A; 50 μm in F; 10 μm in K.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Images depicting Iba1 immunostaining in the AVCN in control and experimental animals. In the ipsilateral side, Iba1 immunostaining increased at 1d post-lesion (arrows in C) and peaked around 4d (arrows in D) in comparison with the contralateral side and unoperated animals (arrows in A,B). Iba1 levels remained elevated at 7d (arrows in E) and decreased at 15d (arrows in F) post-lesion. The morphological features of these cells are shown in G–K. Particularly at 7d post-lesion, activated microglial cells assumed very diverse phenotypes (compare asterisk and arrows in E). The inset in A indicates the location of the AVCN, and the square box indicates the approximate locations of the fields represented in A–F. Scale bar = 250 μm in A; 50 μm in F; 10 μm in K.
Mentions: In the control condition and in the side contralateral to the lesion, microglial cells in the AVCN had round or oval cell bodies and long ramified processes (Figures 3A,B,G). A microglial reaction in the ipsilateral AVCN of experimental animals was first detectable 1 day after the lesion, at which time glial cells had larger cell bodies along with thicker and less branched processes than resting microglia (Figures 3C,H). At 4d post-lesion, microglial expression was maximal (Figures 3D,I) when compared to that in the intact side (Figure 3B) and control (Figure 3A) animals. Cells were larger, darker and occupied a larger area when compared to those observed at 1d post-lesion. These qualitative observations were confirmed by significant increases in their cross-sectional area, mean gray level of Iba1 immunostaining and immunostained area (Figure 4; Table 2). At 7d post-lesion, glial cells displayed a remarkable heterogeneity in their morphology. Some cells had smaller cell bodies and longer processes (arrowheads in Figures 3E,J) while others had morphologies resembling those seen at 1 and 4 d post-lesion (compare asterisk and arrows in Figure 3E). At this time point, the microglial cross-sectional area was significantly decreased when compared with the other survival time points. However, it was increased when compared with the unmanipulated side and control animals (Figures 3, 4; Table 2). Glial cells were still darkly immunostained as confirmed by significant decreases in the mean gray levels when compared with experimental animals at 4d post-lesion, but no differences were found when compared with 1d post-lesion animals (Figure 4; Table 2). At longer survival times (15d post-lesion), microglial cells adopted the typical ramified structure usually seen in the normal brain (Figures 3F,K, 4).

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