Research reportPSA-NCAM expression in the piriform cortex of the adult rat. Modulation by NMDA receptor antagonist administration
Introduction
The neural cell adhesion molecule (NCAM) is a membrane bound glycoprotein that mediates cell to cell and cell to extracellular matrix interactions [12], [42]. This protein is capable of incorporating long chains of α2,8 polysialic acid (PSA) [14]. The presence of this carbohydrate confers anti-adhesive properties to NCAM [41] and consequently it has been implicated in several developmental events such as neuronal migration [35], synaptogenesis [27], [47] or axonal outgrowth and fasciculation [13], [52]. Consequently, PSA-NCAM is expressed in some regions of the adult brain that retain the capability to undergo structural changes, such as the hypothalamus [1], the hippocampus [43] or the piriform cortex [44].
It has been shown that there is a significant increase in the number of PSA-NCAM expressing neurons in the adult rat medial temporal cortex, which contains the piriform cortex, after spatial learning [16], [33] and a similar effect has been found in the dentate gyrus [15]. Furthermore, we have recently shown that the number of PSA-NCAM immunoreactive granule neurons in the hippocampus is significantly increased 7 days after the administration of an NMDA receptor antagonist [31]. NMDA antagonist treatment also increases neurogenesis in the adult dentate gyrus [10], which may contribute to the increase in PSA-NCAM expression, since newly generated granule neurons express PSA-NCAM [45]. Nevertheless, part of the increase in the number of PSA-NCAM immunoreactive neurons is also likely to be due to an upregulation of the expression of this molecule in preexisting neurons.
NMDA receptors play a key role in several events in the central nervous system, such as neuronal birth and migration [23]. Antagonists to these glutamate receptors have been also shown to interfere with targeting and pruning of axons and regulation of synaptogenesis during development [9], [11], [48]. NMDA receptor antagonists also induce axonal sprouting during adulthood [25], [49] and appear to be critical for some processes related to learning such as LTP [3].
The main objectives of this study were to perform a detailed anatomical characterization of PSA-NCAM expression in the piriform cortex, and determine whether NMDA receptor antagonist treatment can influence its expression in this region. The piriform cortex is an area characterized by the presence of axonal outgrowth and synaptic reorganization in response to physiological or experimental manipulations [18]. Consequently, several molecules related to neural plasticity such as GAP-43 [4], MAP1-B [32], rCRMP-4/Tuc4 [30] or PSA-NCAM [44] have been found in the piriform cortex of the adult rat. PSA-NCAM immunoreactivity appears highly down-regulated after development, although it is still expressed in certain neuronal populations of layers II and III of the adult piriform cortex. Previous reports have described PSA-NCAM immunoreactivity in small- and medium-sized neurons. Some of these immunoreactive cells in layer II resembled semilunar or fusiform neurons [44]. In a recent study we have found that PSA-NCAM is expressed in the piriform cortex by many other populations than those described previously, such as neurogliaform neurons [30], thus one of the objectives of this study is to characterize in detail the cellular populations expressing the polysialylated form of NCAM in the adult piriform cortex.
Our results demonstrate that, apart from semilunar and fusiform neurons, some other cell types in the piriform cortex express PSA-NCAM, such as neurogliaform cells in layer II and big interneuron-like cells in layer III. Moreover, we have found PSA-NCAM-expressing cells resembling migratory neuroblasts in layer III and endopiriform nucleus. These cells do not show immunoreactivity for NeuN, a marker of differentiated neurons and they co-express doublecortin (DCX), a protein involved in neuronal migration and differentiation. Administration of an NMDA receptor antagonist induces a significant increase in the number of cells expressing PSA-NCAM in the piriform cortex layer II 7 days after the treatment and also increases the number of DCX-expressing cells in the deep layers of the piriform cortex in animals surviving for 21 days.
Section snippets
Animals and treatments
Twenty-five young adult male Sprague–Dawley rats (200–250 g; Charles River Laboratory) were used in this study. All animal experimentation was conducted in accordance with the National Institutes of Health (NIH) Guide for the Care and use of Laboratory Animals (NIH Publication 85-23, revised 1985) and was approved by the Committee on Animal research of the Rockefeller University. The rats were injected with the competitive NMDA receptor antagonist CGP43487 (5 mg/kg i.p.) in saline. The animals
Results
The piriform or olfactory cortex is a three-layered paleocortical region in which fiber systems and neuronal cell types are highly segregated within layers. Afferent fibers coming from the lateral olfactory tract and other cortical regions make synapses in layer I, an area almost devoid of neuronal somata [38], [51]. Layer II is formed by densely packed neurons with semilunar, pyramidal and fusiform morphology. Many small neurons (neurogliaform cells) with irregular axonal trajectories also
Discussion
Our study describes in detail the neuronal populations expressing PSA-NCAM in the piriform cortex of the adult rat. The presence of this molecule in many neurons of layer II and its co-existence with molecules implicated in axonal outgrowth suggests that these neurons are undergoing structural plasticity during adulthood. Administration of an NMDA receptor antagonist significantly increases the number of PSA-NCAM immunoreactive cells in the piriform cortex layer II, suggesting that PSA-NCAM
Acknowledgements
This study was supported by a P50 MH58911-01A1 grant to BMc and a PM97-0104 Spanish DGESIC grant. Juan Nacher was recipient of a postdoctoral fellowship from the Valencian Conselleria de Cultura Educacio i Ciencia and a short term fellowship from the Human Frontier Science Program. The authors wish to thank Drs. G. Rougon and C. Walsh for the generous gift of anti PSA and anti DCX antibodies, respectively.
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