ABSTRACT
Feeding C57Bl/6 J mice the copper chelator cuprizone leads to selective apoptosis of mature oligodendrocytes and concomitant demyelination predominantly in the corpus callosum. The process of oligodendrocyte apoptosis in this animal model for multiple sclerosis (MS) involves early microglial activation, but no infiltration of T-lymphocytes. Therefore, this model could mimic early stages of oligodendrocyte degeneration Affected oligodendrocytes express the common neurotrophin receptor, p75(NTR), a 'stress-receptor' which under certain circumstances can induce apoptosis. Only affected oligodendrocytes in MS lesions and MS animal models express this receptor. In order to study the significance of p75(NTR) in the fate of oligodendrocytes, we have exposed wild-type as well as p75(NTR)-knockout mice to a 0.2% (w/w) cuprizone diet and performed a comparative immunohistochemical analysis of the corpus callosum at various time points. Surprisingly, our results show that the absence of p75(NTR) did not alter cuprizone-induced oligodendrocyte death (and subsequent de- or remyelination). Apparently, intracellular apoptosis pathways in adult oligodendrocytes do not require p75(NTR) activated signal transduction in the absence of T-lymphocytes and T-lymphocyte derived cytokines.
Subject(s)
Apoptosis , Demyelinating Diseases/pathology , Demyelinating Diseases/physiopathology , Oligodendroglia/pathology , Receptor, Nerve Growth Factor/genetics , Animals , Corpus Callosum/pathology , Cuprizone , Demyelinating Diseases/chemically induced , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Monoamine Oxidase Inhibitors , Nerve Regeneration , T-Lymphocytes/pathologyABSTRACT
With the aim to study the cellular mechanism underlying the process of muscle spindle regeneration, dorsal root ganglia (DRG) neurons derived from 16-day rat embryos were cocultured with developing myotubes in a compartmentalized culture device. To accomplish the selective survival and neurite formation of the proprioceptive subpopulation, the neurotrophic factor, neurotrophin-3, was added to the culture medium. It appeared that the proprioceptive DRG neurons could develop specialized, Ia afferent terminal-like contacts with myotubes. However, these interactions were scarce and did not result in the induction of differentiation of the contacted myotubes into intrafusal fibers as normally occurs during in vivo development. The present coculture setup apparently lacks appropriate regulatory factors essential for the proper matching of sensory axons and intrafusal fiber precursors and the induction of a functional sensory myoneural connection.
Subject(s)
Embryo, Mammalian/physiology , Ganglia, Spinal/embryology , Muscle Fibers, Skeletal/physiology , Muscles/embryology , Neurons, Afferent/physiology , Proprioception/physiology , Animals , Cell Survival , Coculture Techniques , Embryo, Mammalian/cytology , Embryo, Mammalian/ultrastructure , Ganglia, Spinal/cytology , Muscle Spindles/physiology , Muscles/cytology , Nerve Growth Factors/physiology , Neurites/physiology , Neuromuscular Junction/physiology , Neuromuscular Junction/ultrastructure , Neuronal Plasticity , Neurotrophin 3 , Rats/embryology , RegenerationABSTRACT
In this study we have examined the calcium-binding protein expression in rat embryonic (E16) dorsal root ganglia (DRG) neurons in vitro in the presence of neurotrophin-3 (NT-3). A comparison was made with the expression of calcium-binding proteins in DRG subpopulations that depended in vitro on nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). Our results show that NT-3 promotes the survival of a DRG subpopulation of which over 75% expresses parvalbumin (PV). The majority of these PV-positive NT-3-dependent DRG neurons were large 'type A' neurons. Expression of calbindin-D28k (CaBP) and calretinin (Calr) in the NT-3-dependent DRG population was seen in smaller fractions (between 12 and 17%) of the surviving DRG neurons and in both type A and B neurons. The preferential expression of PV in NT-3-dependent type A neurons is unique in comparison to the expression of PV and the other calcium-binding proteins in DRG neurons surviving in vitro in the presence of NGF or BDNF.
