The central nervous system consists of two major cell populations: nerve cells and glial cells. Glial cells are subdivided into astrocytes, microglia and oligodendrocytes. Dysfunction and death of nerve cells and glia in the brain is a major determinant of the symptoms that develop in most neurological disorders. Studies in our laboratory are focused on the role of astrocytes in brain diseases, particularly in motor neuron disease. Astrocytes greatly outnumber neurons and play many roles essential for normal brain function. These cells make important contributions to activities including provision of precursors for amino acid neurotransmitters, buffering of ionic changes in the extracellular fluid and metabolite trafficking from the blood. Studies in recent years have revealed additional complexities in the interchange of metabolites and intercellular messengers between astrocytes and neurons, further demonstrating the important influences of astrocytes on neuronal function.
Astrocytes are also the major contributor to defence against oxidative damage and express glutamate transporters that clear excess glutamate from the synaptic cleft and the extracellular space. Loss of these transporters leads to excitotoxic damage. Thus, the extent of preservation of key astrocytic properties and the ability of these cells to mount appropriate defensive responses are likely to be important determinants of tissue viability in many neurological diseases.
Muyderman H, Chen T (2014) Mitochondrial dysfunction in amyotrophic lateral sclerosis - a valid pharmacological target? British Journal of Pharmacology, 171(8):2191-205
Peiris H, Dubach D, Jessup CF, Unterweger P, Raghupathi R, Muyderman H, Zanin MP, Mackenzie K, Pritchard MA, Keating DJ (2014) RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells. Oxidative Medicine & Cellular Longevity, 2014:520316
Malmevik J, Rogers ML, Sims N, Rush RA, Nakanishi Y, Nilsson M, Muyderman H (2014) Selective transfection of microglia in the brain using an antibody-based non-viral vector. Brain Research, 1586:12-22
Muyderman H, Sims NR, Tanaka M, Fuku N, Raghupathi R, Thyagarajan D (2012) The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis. Mitochondrion, 12(4):465-71
Muyderman H, Yew WP, Homkajorn B and Sims NR (2010) Astrocytic responses to DNA delivery using Nucleofection. Neurochemical Research, 35(11):1771-1779
Homkajorn B, Sims NR and Muyderman H (2010) Connexin 43 regulates astrocytic migration and proliferation in response to injury. Neuroscience Letters, 486(3):197-201
Sims NR and Muyderman H (2010) Mitochondria, oxidative metabolism and cell death in stroke. Biochimica et Biophysica Acta, 1802(1):80-91
Rogers M-L, Bailey S, Matusica D, Nicholson I, Muyderman H, Pagadala PC, Neet KE, Zola H, Macardle P and Rush RA (2010) ProNGF mediates death of Natural Killer cells through activation of the p75NTR-Sortlin complex. Journal of NeuroImmunology, 226(1-2):93-103