Journal Club: Schwann cells increase, neurons decrease and macrophages change in genetic form of Vestibular Schwannoma (NF2-SWN)

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Today's journal article

Al-Asad RK, Montigny DJ, O'Malley JT, Welling DB, Jung DH, Eckhard AH, Kempfle JS. "Investigating cochlear cellular dynamics in neurofibromatosis type 2-associated schwannomatosis: a histopathological study. "

Why I picked this article

This is a very valuable study, characterising what is happening in the inner ear of a human patient with a very special form of vestibular schwannoma. Schwann cells are glial cells that provide myelination of the auditory neurons. In this case, however, Schwann cells have undergone pathological change to become a benign tumour. These publications provide valuable insight into changes in key cellular members of Schwannoma in a way (spiral ganglion neurons, Schwann cells) in the cochlea of patients with a genetic form of vestibular schwannoma. In addition, what was also interesting was the focus on the macrophage, drawing into a hypothesis that macrophages play a role in tumour pathophysiology. 

Our inner ear (containing the cochlea and vestibular system) is difficult to access, and limited scientific work is available. Post-mortem temporal bone from patients who were diagnosed with NF2-SWN must be so rare globally, and this study draws on the amazing science resource archived and available from the Massachusetts Eye and Ear Temporal Bone Registry. 

Some of the research findings

This study characterised the temporal bone from patients with neurofibromatosis type 2-associated schwannomatosis (NF2-SWN). Of 28 cases with unilateral or bilateral vestibular schwannoma cases in the Massachusetts Eye and Ear Temporal Bone Registry archive, they identified 3 cases of confirmed NF2-SWN that they have further investigated using immunohistochemistry and compared against normal, age-matched cases. 

Using markers, they have investigated the cell densities of:

  • Spiral ganglion neurons (Beta-Tubullin III, “TUJ1,” neuronal marker, 1:250, Biolegend 801,202, RRID: AB_2313773)
  • Schwann cells (Rabbit-anti-SOX10m glial marker, 1:100, Abcam 227,680, RRID: AB_2927464)
  • Macropages (Rabbit-anti-IBA1, macrophage marker,1:100, Invitrogen MA5-27726)

After quantifications, observation is that there are statistical changes to the densities of spiral ganglion neurons, Schwann cells and the ramification index of macrophages. Immunohistochemistry data look beautiful and very nice. It is interesting to note that qualitatively, macrophage labelling (with IBA1 as marker) looks very different in terms of labelling pattern between control and NF2-SWN groups without quantification. However, the macrophage density as counted by IBA1/DAPI double labeling per unit area did not show statistical significance, and ramification index needed to be shown. 

Figures adopted from parts of Figure 2A and Figure 3A. 

Haruna's takeaway

It was really valuable, first of all, to read about NF2-SWN: 

  • neurofibromatosis type 2-associated schwannomatosis (NF2-SWN), schwannoma associated with variations in NF2 gene (Mcclatchey AI, Giovannini M. Genes Dev. (2005) 19:2265–77)
  • NF2-SWN is autosomal dominant
  • 95% of cases involve bilateral schwannoma before age of 30 (Baser ME, Friedman JM, Joe H, Shenton A, Wallace AJ, Ramsden RT, et al. Genet Med. (2011) 13:576–81)

Data provided here is highly valuable, considering how rare NF2-SWN must be, in addition to how rare it is to be able to collect and study enough temporal bones from humans for scientific research. 

Vestibular schwannomas occur in patients in New Zealand, too; our clinical research colleagues have mentioned that they have surgical removal of vestibular schwannoma at least once/month or so. Once large enough, vestibular schwannomas need to be extracted as part of treatment, and we have discussed in the past whether there is a scientific need /benefit to collecting and analysing these tissues after surgery. We will watch this space on vestibular schwannoma to assess if there is any opportunity for us from New Zealand to make contributions to the field. 


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This is Haruna's 2/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.