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Distribution of parvalbumin and calretinin immunoreactive interneurons in motor cortex from multiple sclerosis post-mortem tissue

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Abstract

Parvalbumin (PV) and calretinin (CR) are calcium binding proteins (CBP’s) expressed in discrete GABAergic interneuron populations in the human cortex. CBP’s are known to buffer calcium concentrations and protect neurons from increases in intracellular calcium. Perturbations in intracellular calcium can activate proteolytic enzymes including calpain, leading to deleterious effects to axons. Ca++-mediated mechanisms have been found to be associated with axonal pathology in MS and the restructuring of calcium channels has been shown to occur in experimental autoimmune encephalomyelitis (EAE) as well as multiple sclerosis tissue. Previous data indicates a reduction in the expression of the parvalbumin gene as well as reduced extension of neurites on parvalbumin expressing interneurons within multiple sclerosis normal appearing grey matter (NAGM). Modifications in interneuron parvalbumin or calretinin levels could change calcium buffering capacity, as well as the way these cells respond to neuronal insults. The present study was designed to compare CBP immunoreactive neurons in normal and multiple sclerosis post-mortem NAGM. To this end, we utilized immunofluorescent staining and high resolution confocal microscopy to map regions of the human motor cortex, and characterize layer specific CBP distribution in the normal and multiple sclerosis motor cortex. Our results indicate a significant reduction in the number of PV interneurons within layer 2 of the multiple sclerosis primary motor cortex with no concurrent change in number of calretinin positive neurons.

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References

  • Amitai Y, Gibson JR, Beierlein M, Patrick SL, Ho AM, Connors BW (2002) The spatial dimensions of electrically coupled networks of interneurons in the neocortex. J Neurosci 22(10):4142–4152

    PubMed  CAS  Google Scholar 

  • Baldellon C, Alattia JR, Strub MP, Pauls T, Berchtold MW, Cave A, Padilla A (1998) 15N NMR Relaxation studies of calcium-loaded parvalbumin show tight dynamics compared to those of other EF-hand proteins. Biochem 37:9964–9975

    Article  CAS  Google Scholar 

  • Beers DR, Ho B, Siklos L, Alexianu ME, Mosier DR, Mohamed AH, Otsuka Y, Kozovska ME, McAlhany RE, Smith RG, Appel SH (2001) Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amytrophic lateral sclerosis. J Neurochem 79:499–509

    Article  PubMed  CAS  Google Scholar 

  • Brand-Scheiber E, Werner P (2004) Calcium channel blockers ameliorate disease in a mouse model of multiple sclerosis. Exp Neurol 189:5–9

    Article  Google Scholar 

  • Bu J, Sathyendra V, Nagykery N, Geula C (2003) Age-related changes in calbindin-D28k, calretinin, and parvalbumin-immunoreactive neurons in the human cerebral cortex. Exdp Neurol 182:220–231

    Article  CAS  Google Scholar 

  • Caramia MD, Palmieri MG, Desiato MT, Boffa L, Galizia P, Rossini PM, Centonze D, Bernardi G (2004) Brain excitability changes in the relapsing and remitting phases of multiple sclerosis: a study with transcranial magnetic stimulation. Clin Neurophys 115:956–965

    Article  Google Scholar 

  • Chard DT, Griffin CM, Parker GJM, Kapoor R, Thompson AJ, Miller DH (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125:327–337

    Article  PubMed  CAS  Google Scholar 

  • Cotter D, Landau S, Beasley C, Stevenson R, Chana G, MacMillan L, Everall I (2002) The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cortex in major depressive disorder, bipolar disorder, and schiozophrenia. Soc Biol Psych 51:377–386

    Article  CAS  Google Scholar 

  • Craner MJ, Hains BC, Lo AC, Black JA, Waxman SG (2004) Co-localization of sodium channel Nav1.6 and the sodium–calcium exchanger at sites of axonal injury in the spinal cord in EAE. Brain 127:294–303

    Article  PubMed  Google Scholar 

  • DeFelipe J (1997) Types of neurons, synaptic connections and chemical characteristics of cells immunoreactive for calbindin-D28K, parvalbumin and calretinin in the neocortex. J Chem Neuroanat 14:1–19

    Article  PubMed  CAS  Google Scholar 

  • Dekkers J, Bayley P, Dick JRT, Schwaller B, Berchtold MW, Greensmith L (2004) Over-expression of parvalbumin in transgenic mice rescues motoneurons from injury-induced cell death. Neuroscience 123:459–466

    Article  PubMed  CAS  Google Scholar 

  • del Rio MR, DeFelipe J (1997) Colocalization of parvalbumin and calbindin D-28k in neurons including chandelier cells of the human temporal cortex. J Chem Neuroanat 12:165–173

    Article  PubMed  Google Scholar 

  • Dutta R, Mcdonough J, Yin X, Peterson J, Chang A, Torres T, Gudz T, Macklin WB, Lewis DA, Fox RJ, Rudick R, Mirnics K, Trapp BD (2006) Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 59:478–489

    Article  PubMed  CAS  Google Scholar 

  • Eyels DW, Mcgrath JJ, Reynolds GP (2002) Neuronal calcium-binding proteins and schizophrenia. Schizophr Res 57:27–34

    Article  Google Scholar 

  • Gilgun-Sherki Y, Melamed E, Offen D (2004) The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 251:261–268

    Article  PubMed  CAS  Google Scholar 

  • Grateron L, Cebada-Sanchez S, Marcos P, Mohedano-Moriano A, Insausti AM, Munoz M, Arroyo-Jimenez MM, Martinez-Marcos A, Artacho-Pertula E, Blaizot X, Insausti R (2003) Postnatal development of calcium-binding proteins immunoreactivity (parvalbumin, calbindin, calretinin) in the human entorhinal cortex. J Chem Neuroanat 26:311–316

    Article  PubMed  CAS  Google Scholar 

  • Ibrahim SM, Mix E, Bottcher T, Koczan D, Gold R, Rolfs A, Thiesen H-J (2001) Gene expression profiling of the nervous system in murine experimental autoimmune encephalomyelitis. Brain 124:1927–1938

    Article  PubMed  CAS  Google Scholar 

  • Isaev NK, Andreeva NA, Stel’mashuk EV, Zorov DB (2005) Role of mitochondria in the mechanisms of glutamate toxicity. Biochemistry (Mosc) 70(6):611–618

    Article  CAS  Google Scholar 

  • Kornek B, Storch M, Bauer J, Djamshidian A, Weissert R, Wallstroem E, Stefferl A, Zimprich F, Olsson T, Linington C, Schmidbauer M, Lassman H (2001) Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain 124:1114–1124

    Article  PubMed  CAS  Google Scholar 

  • Liepert J, Mingers D, Hensen C, Baumer T, Weiller C (2005) Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study. Mult Scler 11:316–321

    Article  PubMed  CAS  Google Scholar 

  • Porter LL, Matin D, Asaf K (2000) Characteristics of GABAergic neurons and their synaptic relationships with intrinsic axons in the cat motor cortex. Somatosens Mot Res 17:67–81

    Article  PubMed  CAS  Google Scholar 

  • Rosin C, Bates TE, Skaper SD (2004) Excitatory amino acid induced oligodendrocyte cell death in vitro: receptor-dependant and -independent mechanisms. J Neurochem 90:1173–1185

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D (2005) Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3T. Brain 128:1016–1025

    Article  PubMed  Google Scholar 

  • Zaitsev AV, Gonzalez-Burgos G, Povysheva NV, Kroner S, Lewis DA, Krimer LS (2005) Localization of calcium-binding proteins in physiologically and morphologically characterizaed interneurons of monkey dorsolateral prefrontal cortex. Cereb Cortex 15:1178–1186

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to express our gratitude to the Kathleen Price Bryan Brain Bank and Rocky Mountain MS center for kindly donating tissue for this study. We would also like to especially thank the donors and families for granting access to the tissue as well as the National Multiple Sclerosis Society and EMD Serono, INC for providing funding for this project.

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Authors and Affiliations

  1. Oak Clinic for Multiple Sclerosis Research, School of Biomedical Sciences, Kent State University, Kent, OH, 44242, USA

    Jennifer McDonough & Ernest J. Freeman

  2. Department of Biological/Biomedical Sciences, A330 Cunningham Hall, Kent State University, Kent, OH, 44224, USA

    Robert J. Clements

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  1. Robert J. Clements
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  2. Jennifer McDonough
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  3. Ernest J. Freeman
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Correspondence to Robert J. Clements.

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Clements, R.J., McDonough, J. & Freeman, E.J. Distribution of parvalbumin and calretinin immunoreactive interneurons in motor cortex from multiple sclerosis post-mortem tissue. Exp Brain Res 187, 459–465 (2008). https://doi.org/10.1007/s00221-008-1317-9

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  • DOI: https://doi.org/10.1007/s00221-008-1317-9

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