%0 Journal Article
%T VGLUTs in Peripheral Neurons and the Spinal Cord: Time for a Review
%A Pablo R. Brumovsky
%J ISRN Neurology
%D 2013
%R 10.1155/2013/829753
%X Vesicular glutamate transporters (VGLUTs) are key molecules for the incorporation of glutamate in synaptic vesicles across the nervous system, and since their discovery in the early 1990s, research on these transporters has been intense and productive. This review will focus on several aspects of VGLUTs research on neurons in the periphery and the spinal cord. Firstly, it will begin with a historical account on the evolution of the morphological analysis of glutamatergic systems and the pivotal role played by the discovery of VGLUTs. Secondly, and in order to provide an appropriate framework, there will be a synthetic description of the neuroanatomy and neurochemistry of peripheral neurons and the spinal cord. This will be followed by a succinct description of the current knowledge on the expression of VGLUTs in peripheral sensory and autonomic neurons and neurons in the spinal cord. Finally, this review will address the modulation of VGLUTs expression after nerve and tissue insult, their physiological relevance in relation to sensation, pain, and neuroprotection, and their potential pharmacological usefulness. 1. How VGLUTs Became the ˇ°Gold Standardˇ± for the Identification of Glutamatergic Neurons Before focusing on the presence and role of vesicular glutamate transporters in neurons in the periphery and the spinal cord, it is important to begin with some historical facts on how it was that glutamatergic neurons were identified in the nervous system. Several decades of research established that glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) [1] and PNS, including dorsal root ganglion (DRG) and spinal cord neurons [2, 3]. However, the morphological phenotyping of glutamatergic neurons as well as glial cells was not to be a trivial matter. First in accomplishing a major breakthrough were Storm-Mathisen, Ottersen, and their colleagues who, by means of careful electron microscopy methodologies and meticulous analysis, demonstrated glutamate-like immunoreactivity (Li) in several areas of the mouse, rat, guinea pig, and monkey brain and, importantly, its association to synapses [4¨C6]. This pioneering work led to the distinction of a ˇ°transmitter poolˇ± in glutamatergic terminals, a ˇ°metabolic poolˇ± in nonglutamatergic neurons, and a ˇ°glial poolˇ± [7¨C9]. It also prompted the immunohistochemical analysis in sensory neurons, using antibodies against glutamate [10¨C14]. Subsequent methods to identify glutamatergic neurons were based on the immunohistochemical detection of enzymes like glutaminase, involved in the
%U http://www.hindawi.com/journals/isrn.neurology/2013/829753/