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Published in: Acta Neuropathologica Communications 1/2015

Open Access 01-12-2015 | Research

Differential expression of galanin in the cholinergic basal forebrain of patients with Lewy body disorders

Authors: Athanasios Alexandris, Alan King Lun Liu, Raymond Chuen-Chung Chang, Ronald K. B. Pearce, Steve M. Gentleman

Published in: Acta Neuropathologica Communications | Issue 1/2015

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Abstract

Introduction

Depletion of cholinergic neurons within the nucleus basalis of Meynert (nbM) is thought to contribute to the development of cognitive impairments in both Alzheimer’s disease (AD) and Lewy body disorders (LBD). It has been reported that, in late stage AD, a network of fibres that contain the neuropeptide galanin displays significant hypertrophy and ‘hyperinnervates’ the surviving cholinergic neurons. Galanin is considered as a highly inducible neuroprotective factor and in AD this is assumed to be part of a protective tissue response. The aim of this study was to determine if a similar galanin upregulation is present in the nbM in post-mortem tissue from patients with LBD. Gallatin immunohistochemistry was carried out on anterior nbM sections from 76 LBD cases (27 PD, 15 PD with mild cognitive impairment (MCI), 34 PD with dementia (PDD) and 4 aged-matched controls. Galaninergic innervation of cholinergic neurons was assessed on a semi-quantitative scale.

Results

The LBD group had significantly higher galaninergic innervation scores (p = 0.016) compared to controls. However, this difference was due to increased innervation density only in a subgroup of LBD cases and this correlated positively with choline acetyltransferase–immunopositive neuron density.

Conclusion

Galanin upregulation within the basal forebrain cholinergic system in LBD, similar to that seen in AD, may represent an intrinsic adaptive response to neurodegeneration that is consistent with its proposed roles in neurogenesis and neuroprotection.
Appendix
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Literature
2.
go back to reference Liu AK, Chang RC, Pearce RK, Gentleman SM. Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease. Acta Neuropathol. 2015;129:527–40.PubMedCentralCrossRefPubMed Liu AK, Chang RC, Pearce RK, Gentleman SM. Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease. Acta Neuropathol. 2015;129:527–40.PubMedCentralCrossRefPubMed
3.
go back to reference Arendt T, Bruckner MK, Bigl V, Marcova L. Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer’s disease. II. Ageing, Korsakoff’s disease, Parkinson’s disease, and Alzheimer’s disease. J Comp Neurol. 1995;351:189–222.CrossRefPubMed Arendt T, Bruckner MK, Bigl V, Marcova L. Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer’s disease. II. Ageing, Korsakoff’s disease, Parkinson’s disease, and Alzheimer’s disease. J Comp Neurol. 1995;351:189–222.CrossRefPubMed
4.
go back to reference Arendt T, Bigl V, Arendt A, Tennstedt A. Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s Disease. Acta Neuropathol. 1983;61:101–8.CrossRefPubMed Arendt T, Bigl V, Arendt A, Tennstedt A. Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s Disease. Acta Neuropathol. 1983;61:101–8.CrossRefPubMed
5.
go back to reference Arendt T, Zvegintseva HG, Leontovich TA. Dendritic changes in the basal nucleus of Meynert and in the diagonal band nucleus in Alzheimer’s disease--a quantitative Golgi investigation. Neuroscience. 1986;19:1265–78.CrossRefPubMed Arendt T, Zvegintseva HG, Leontovich TA. Dendritic changes in the basal nucleus of Meynert and in the diagonal band nucleus in Alzheimer’s disease--a quantitative Golgi investigation. Neuroscience. 1986;19:1265–78.CrossRefPubMed
6.
go back to reference Theofilas P, Dunlop S, Heinsen H, Grinberg LT. Turning on the light within: subcortical nuclei of the isodentritic core and their role in Alzheimer’s disease pathogenesis. J Alzheimers Dis. 2015. Theofilas P, Dunlop S, Heinsen H, Grinberg LT. Turning on the light within: subcortical nuclei of the isodentritic core and their role in Alzheimer’s disease pathogenesis. J Alzheimers Dis. 2015.
7.
go back to reference Chan-Palay V. Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer’s and Parkinson’s disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol. 1988;273:543–57.CrossRefPubMed Chan-Palay V. Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer’s and Parkinson’s disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol. 1988;273:543–57.CrossRefPubMed
8.
go back to reference Mufson EJ, Cochran E, Benzing W, Kordower JH. Galaninergic innervation of the cholinergic vertical limb of the diagonal band (Ch2) and bed nucleus of the stria terminalis in aging, Alzheimer’s disease and Down’s syndrome. Dementia. 1993;4:237–50.PubMed Mufson EJ, Cochran E, Benzing W, Kordower JH. Galaninergic innervation of the cholinergic vertical limb of the diagonal band (Ch2) and bed nucleus of the stria terminalis in aging, Alzheimer’s disease and Down’s syndrome. Dementia. 1993;4:237–50.PubMed
9.
go back to reference Kordower JH, Le HK, Mufson EJ. Galanin immunoreactivity in the primate central nervous system. J Comp Neurol. 1992;319:479–500.CrossRefPubMed Kordower JH, Le HK, Mufson EJ. Galanin immunoreactivity in the primate central nervous system. J Comp Neurol. 1992;319:479–500.CrossRefPubMed
10.
go back to reference Gentleman SM, Falkai P, Bogerts B, Herrero MT, Polak JM, Roberts GW. Distribution of galanin-like immunoreactivity in the human brain. Brain Res. 1989;505:311–5.CrossRefPubMed Gentleman SM, Falkai P, Bogerts B, Herrero MT, Polak JM, Roberts GW. Distribution of galanin-like immunoreactivity in the human brain. Brain Res. 1989;505:311–5.CrossRefPubMed
11.
go back to reference Gabriel SM, Bierer LM, Davidson M, Purohit DP, Perl DP, Harotunian V. Galanin-like immunoreactivity is increased in the postmortem cerebral cortex from patients with Alzheimer’s disease. J Neurochem. 1994;62:1516–23.CrossRefPubMed Gabriel SM, Bierer LM, Davidson M, Purohit DP, Perl DP, Harotunian V. Galanin-like immunoreactivity is increased in the postmortem cerebral cortex from patients with Alzheimer’s disease. J Neurochem. 1994;62:1516–23.CrossRefPubMed
12.
go back to reference Bersani M, Johnsen AH, Hojrup P, Dunning BE, Andreasen JJ, Holst JJ. Human galanin: primary structure and identification of two molecular forms. FEBS Lett. 1991;283:189–94.CrossRefPubMed Bersani M, Johnsen AH, Hojrup P, Dunning BE, Andreasen JJ, Holst JJ. Human galanin: primary structure and identification of two molecular forms. FEBS Lett. 1991;283:189–94.CrossRefPubMed
13.
go back to reference Schmidt WE, Kratzin H, Eckart K, Drevs D, Mundkowski G, Clemens A, et al. Isolation and primary structure of pituitary human galanin, a 30-residue nonamidated neuropeptide. Proc Natl Acad Sci U S A. 1991;88:11435–9.PubMedCentralCrossRefPubMed Schmidt WE, Kratzin H, Eckart K, Drevs D, Mundkowski G, Clemens A, et al. Isolation and primary structure of pituitary human galanin, a 30-residue nonamidated neuropeptide. Proc Natl Acad Sci U S A. 1991;88:11435–9.PubMedCentralCrossRefPubMed
14.
17.
go back to reference Branchek TA, Smith KE, Gerald C, Walker MW. Galanin receptor subtypes. Trends Pharmacol Sci. 2000;21:109–17.CrossRefPubMed Branchek TA, Smith KE, Gerald C, Walker MW. Galanin receptor subtypes. Trends Pharmacol Sci. 2000;21:109–17.CrossRefPubMed
19.
go back to reference Counts SE, Perez SE, Ginsberg SD, Mufson EJ. Neuroprotective role for galanin in Alzheimer’s disease. EXS. 2010;102:143–62.PubMedCentralPubMed Counts SE, Perez SE, Ginsberg SD, Mufson EJ. Neuroprotective role for galanin in Alzheimer’s disease. EXS. 2010;102:143–62.PubMedCentralPubMed
20.
go back to reference Alafuzoff I, Ince PG, Arzberger T, Al-Sarraj S, Bell J, Bodi I, et al. Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathol. 2009;117:635–52.CrossRefPubMed Alafuzoff I, Ince PG, Arzberger T, Al-Sarraj S, Bell J, Bodi I, et al. Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathol. 2009;117:635–52.CrossRefPubMed
21.
go back to reference Daniel SE, Lees AJ. Parkinson’s disease society brain bank, London: overview and research. J Neural Transm Suppl. 1993;39:165–72.PubMed Daniel SE, Lees AJ. Parkinson’s disease society brain bank, London: overview and research. J Neural Transm Suppl. 1993;39:165–72.PubMed
22.
go back to reference Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22:1689,707. quiz 1837.CrossRef Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22:1689,707. quiz 1837.CrossRef
23.
go back to reference Litvan I, MacIntyre A, Goetz CG, Wenning GK, Jellinger K, Verny M, et al. Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study. Arch Neurol. 1998;55:969–78.CrossRefPubMed Litvan I, MacIntyre A, Goetz CG, Wenning GK, Jellinger K, Verny M, et al. Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study. Arch Neurol. 1998;55:969–78.CrossRefPubMed
24.
go back to reference Papapetropoulos S, Gonzalez J, Lieberman A, Villar JM, Mash DC. Dementia in Parkinson’s disease: a post-mortem study in a population of brain donors. Int J Geriatr Psychiatry. 2005;20:418–22.CrossRefPubMed Papapetropoulos S, Gonzalez J, Lieberman A, Villar JM, Mash DC. Dementia in Parkinson’s disease: a post-mortem study in a population of brain donors. Int J Geriatr Psychiatry. 2005;20:418–22.CrossRefPubMed
25.
go back to reference Kalaitzakis ME, Walls AJ, Pearce RK, Gentleman SM. Striatal Abeta peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes. Neurobiol Dis. 2011;41:377–84.CrossRefPubMed Kalaitzakis ME, Walls AJ, Pearce RK, Gentleman SM. Striatal Abeta peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes. Neurobiol Dis. 2011;41:377–84.CrossRefPubMed
26.
go back to reference Kordower JH, Mufson EJ. Galanin-like immunoreactivity within the primate basal forebrain: differential staining patterns between humans and monkeys. J Comp Neurol. 1990;294:281–92.CrossRefPubMed Kordower JH, Mufson EJ. Galanin-like immunoreactivity within the primate basal forebrain: differential staining patterns between humans and monkeys. J Comp Neurol. 1990;294:281–92.CrossRefPubMed
27.
go back to reference Bonnefond C, Palacios JM, Probst A, Mengod G. Distribution of galanin mRNA containing cells and galanin receptor binding sites in human and rat hypothalamus. Eur J Neurosci. 1990;2:629–37.CrossRefPubMed Bonnefond C, Palacios JM, Probst A, Mengod G. Distribution of galanin mRNA containing cells and galanin receptor binding sites in human and rat hypothalamus. Eur J Neurosci. 1990;2:629–37.CrossRefPubMed
28.
29.
go back to reference Bowser R, Kordower JH, Mufson EJ. A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic basal forebrain neurons in Alzheimer’s disease. Brain Pathol. 1997;7:723–30.CrossRefPubMed Bowser R, Kordower JH, Mufson EJ. A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic basal forebrain neurons in Alzheimer’s disease. Brain Pathol. 1997;7:723–30.CrossRefPubMed
30.
go back to reference Counts SE, Chen EY, Che S, Ikonomovic MD, Wuu J, Ginsberg SD, et al. Galanin fiber hypertrophy within the cholinergic nucleus basalis during the progression of Alzheimer’s disease. Dement Geriatr Cogn Disord. 2006;21:205–14.CrossRefPubMed Counts SE, Chen EY, Che S, Ikonomovic MD, Wuu J, Ginsberg SD, et al. Galanin fiber hypertrophy within the cholinergic nucleus basalis during the progression of Alzheimer’s disease. Dement Geriatr Cogn Disord. 2006;21:205–14.CrossRefPubMed
31.
go back to reference Sabbagh MN, Sandhu SS, Farlow MR, Vedders L, Shill HA, Caviness JN, et al. Correlation of clinical features with argyrophilic grains at autopsy. Alzheimer Dis Assoc Disord. 2009;23:229–33.PubMedCentralCrossRefPubMed Sabbagh MN, Sandhu SS, Farlow MR, Vedders L, Shill HA, Caviness JN, et al. Correlation of clinical features with argyrophilic grains at autopsy. Alzheimer Dis Assoc Disord. 2009;23:229–33.PubMedCentralCrossRefPubMed
32.
go back to reference Garcia-Falgueras A, Ligtenberg L, Kruijver FP, Swaab DF. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity. J Comp Neurol. 2011;519:3061–84.CrossRefPubMed Garcia-Falgueras A, Ligtenberg L, Kruijver FP, Swaab DF. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity. J Comp Neurol. 2011;519:3061–84.CrossRefPubMed
33.
go back to reference Henderson Z, Morris N. Galanin-immunoreactive synaptic terminals on basal forebrain cholinergic neurons in the rat. J Comp Neurol. 1997;383:82–93.CrossRefPubMed Henderson Z, Morris N. Galanin-immunoreactive synaptic terminals on basal forebrain cholinergic neurons in the rat. J Comp Neurol. 1997;383:82–93.CrossRefPubMed
34.
go back to reference Liu A, Chang R, Pearce R. Subregional nucleus basalis of Meynert pathology in Lewy Body Disorders [Oral presentation]. The 116th Meeting of the British Neuropathological Society (BNS 2015), London, UK., 4-6 March 2015. In Neuropathology and Applied Neurobiology, 2015;41 Suppl 1:11–12, abstract no. O07. Liu A, Chang R, Pearce R. Subregional nucleus basalis of Meynert pathology in Lewy Body Disorders [Oral presentation]. The 116th Meeting of the British Neuropathological Society (BNS 2015), London, UK., 4-6 March 2015. In Neuropathology and Applied Neurobiology, 2015;41 Suppl 1:11–12, abstract no. O07.
35.
go back to reference Unger JW, Schmidt Y. Galanin-immunoreactivity in the nucleus basalis of Meynert in the rat: age-related changes and differential response to lesion-induced cholinergic cell loss. Neurosci Lett. 1993;153:140–3.CrossRefPubMed Unger JW, Schmidt Y. Galanin-immunoreactivity in the nucleus basalis of Meynert in the rat: age-related changes and differential response to lesion-induced cholinergic cell loss. Neurosci Lett. 1993;153:140–3.CrossRefPubMed
36.
go back to reference de Lacalle S, Kulkarni S, Mufson EJ. Plasticity of galaninergic fibers following neurotoxic damage within the rat basal forebrain: initial observations. Exp Neurol. 1997;146:361–6.CrossRefPubMed de Lacalle S, Kulkarni S, Mufson EJ. Plasticity of galaninergic fibers following neurotoxic damage within the rat basal forebrain: initial observations. Exp Neurol. 1997;146:361–6.CrossRefPubMed
37.
go back to reference Barbelivien A, Vaussy C, Marchalant Y, Maubert E, Bertrand N, Beley A, et al. Degeneration of the basalocortical pathway from the cortex induces a functional increase in galaninergic markers in the nucleus basalis magnocellularis of the rat. J Cereb Blood Flow Metab. 2004;24:1255–66.CrossRefPubMed Barbelivien A, Vaussy C, Marchalant Y, Maubert E, Bertrand N, Beley A, et al. Degeneration of the basalocortical pathway from the cortex induces a functional increase in galaninergic markers in the nucleus basalis magnocellularis of the rat. J Cereb Blood Flow Metab. 2004;24:1255–66.CrossRefPubMed
38.
go back to reference Hartonian I, Mufson EJ, De Lacalle S. Long-term plastic changes in galanin innervation in the rat basal forebrain. Neuroscience. 2002;115:787–95.CrossRefPubMed Hartonian I, Mufson EJ, De Lacalle S. Long-term plastic changes in galanin innervation in the rat basal forebrain. Neuroscience. 2002;115:787–95.CrossRefPubMed
39.
go back to reference Ohno K, Takeda N, Kiyama H, Kubo T, Tohyama M. Occurrence of galanin-like immunoreactivity in vestibular and cochlear efferent neurons after labyrinthectomy in the rat. Brain Res. 1994;644:135–43.CrossRefPubMed Ohno K, Takeda N, Kiyama H, Kubo T, Tohyama M. Occurrence of galanin-like immunoreactivity in vestibular and cochlear efferent neurons after labyrinthectomy in the rat. Brain Res. 1994;644:135–43.CrossRefPubMed
40.
go back to reference de Bilbao F, Jazat F, Lamour Y, Senut MC. Age-related changes in galanin-immunoreactive cells of the rat medial septal area. J Comp Neurol. 1991;313:613–24.CrossRefPubMed de Bilbao F, Jazat F, Lamour Y, Senut MC. Age-related changes in galanin-immunoreactive cells of the rat medial septal area. J Comp Neurol. 1991;313:613–24.CrossRefPubMed
41.
go back to reference Counts SE, He B, Che S, Ginsberg SD, Mufson EJ. Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer’s disease. J Alzheimers Dis. 2009;18:885–96.PubMedCentralPubMed Counts SE, He B, Che S, Ginsberg SD, Mufson EJ. Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer’s disease. J Alzheimers Dis. 2009;18:885–96.PubMedCentralPubMed
42.
go back to reference Chan-Palay V. Neurons with galanin innervate cholinergic cells in the human basal forebrain and galanin and acetylcholine coexist. Brain Res Bull. 1988;21:465–72.CrossRefPubMed Chan-Palay V. Neurons with galanin innervate cholinergic cells in the human basal forebrain and galanin and acetylcholine coexist. Brain Res Bull. 1988;21:465–72.CrossRefPubMed
43.
go back to reference Kowall NW, Beal MF. Galanin-like immunoreactivity is present in human substantia innominata and in senile plaques in Alzheimer’s disease. Neurosci Lett. 1989;98:118–23.CrossRefPubMed Kowall NW, Beal MF. Galanin-like immunoreactivity is present in human substantia innominata and in senile plaques in Alzheimer’s disease. Neurosci Lett. 1989;98:118–23.CrossRefPubMed
44.
go back to reference Walker LC, Rance NE, Price DL, Young 3rd WS. Galanin mRNA in the nucleus basalis of Meynert complex of baboons and humans. J Comp Neurol. 1991;303:113–20.CrossRefPubMed Walker LC, Rance NE, Price DL, Young 3rd WS. Galanin mRNA in the nucleus basalis of Meynert complex of baboons and humans. J Comp Neurol. 1991;303:113–20.CrossRefPubMed
45.
go back to reference Chan-Palay V, Ernfors P, Persson H. Galanin gene expression in the nucleus basalis of meynert in senile dementia of the Alzheimer type. Dement Geriatr Cogn Disord. 1990;1(4):192–6.CrossRef Chan-Palay V, Ernfors P, Persson H. Galanin gene expression in the nucleus basalis of meynert in senile dementia of the Alzheimer type. Dement Geriatr Cogn Disord. 1990;1(4):192–6.CrossRef
46.
go back to reference Villar MJ, Cortes R, Theodorsson E, Wiesenfeld-Hallin Z, Schalling M, Fahrenkrug J, et al. Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin. Neuroscience. 1989;33:587–604.CrossRefPubMed Villar MJ, Cortes R, Theodorsson E, Wiesenfeld-Hallin Z, Schalling M, Fahrenkrug J, et al. Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin. Neuroscience. 1989;33:587–604.CrossRefPubMed
47.
go back to reference Klimaschewski L, Grohmann I, Heym C. Target-dependent plasticity of galanin and vasoactive intestinal peptide in the rat superior cervical ganglion after nerve lesion and re-innervation. Neuroscience. 1996;72:265–72.CrossRefPubMed Klimaschewski L, Grohmann I, Heym C. Target-dependent plasticity of galanin and vasoactive intestinal peptide in the rat superior cervical ganglion after nerve lesion and re-innervation. Neuroscience. 1996;72:265–72.CrossRefPubMed
48.
go back to reference Cortes R, Villar MJ, Verhofstad A, Hokfelt T. Effects of central nervous system lesions on the expression of galanin: a comparative in situ hybridization and immunohistochemical study. Proc Natl Acad Sci U S A. 1990;87:7742–6.PubMedCentralCrossRefPubMed Cortes R, Villar MJ, Verhofstad A, Hokfelt T. Effects of central nervous system lesions on the expression of galanin: a comparative in situ hybridization and immunohistochemical study. Proc Natl Acad Sci U S A. 1990;87:7742–6.PubMedCentralCrossRefPubMed
49.
go back to reference Brecht S, Buschmann T, Grimm S, Zimmermann M, Herdegen T. Persisting expression of galanin in axotomized mamillary and septal neurons of adult rats labeled for c-Jun and NADPH-diaphorase. Brain Res Mol Brain Res. 1997;48:7–16.CrossRefPubMed Brecht S, Buschmann T, Grimm S, Zimmermann M, Herdegen T. Persisting expression of galanin in axotomized mamillary and septal neurons of adult rats labeled for c-Jun and NADPH-diaphorase. Brain Res Mol Brain Res. 1997;48:7–16.CrossRefPubMed
50.
go back to reference Ludwig M, Leng G. Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci. 2006;7:126–36.CrossRefPubMed Ludwig M, Leng G. Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci. 2006;7:126–36.CrossRefPubMed
Metadata
Title
Differential expression of galanin in the cholinergic basal forebrain of patients with Lewy body disorders
Authors
Athanasios Alexandris
Alan King Lun Liu
Raymond Chuen-Chung Chang
Ronald K. B. Pearce
Steve M. Gentleman
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2015
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-015-0249-4

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