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Junior Member
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Join Date: Sep 2006
Location: France, Lyon
Posts: 49
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Junior Member
Join Date: Sep 2006
Location: France, Lyon
Posts: 49
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The important thing is not to stop questioning
Hi Zucchini Flower,
and thanks for the article you sent.
Here are selected lines from an article signed by André Parent & coll. from Laval University, Quebec. Full text and bibliographic references available upon personal request.
Levesque M.,Bédard A.,Cossette M.,Parent A.,
Novel aspects of the chemical anatomy of the striatum and its efferents projections
Journal of Chemical Neuroanatomy, Volume 26, Issue 4 , December 2003, Pages 271-281
andre.parent@anm.ulaval.ca
(....)...The aim of this paper is to provide an overview of the organization of the striatum and its efferent projections. Many of the data presented here stems from experimental studies undertaken in monkeys and rats, but other originate from analyses of human postmortem tissue, including materials from patients that suffered from Huntington's disease (HD).
Neurogenesis in adult striatum
The putative DA neurons that occur in the striatum of monkeys were reportedly devoid of the aging pigment lipofuschin ([Betarbet et al., 1997]), a finding that led to the suggestion that they might represent newly generated neurons.
In normal adult rats and monkeys, new neurons are know to be produced throughout life in two specific areas of the brain: (1) the dentate gyrus of the hippocampus; and (2) the subventricular zone (SVZ) that lines the dorsolateral portion of the lateral ventricles ( [Cameron et al., 1993, Doetsch et al., 1997 and Gould et al., 1999]).
Both of these areas appear to be able to produce new neurons throughout adult life in humans as well ( [Eriksson et al., 1998 and Bernier et al., 2000]). In all species examined thus far, neurons produced in the SVZ migrate into the olfactory bulb via the so-called rostral migratory stream, whereas those generated in the dentate gyrus become integrated as granule cells into the local microcircuitry ( [Cameron et al., 1993, Luskin, 1993, Gould et al., 1999 and Bédard et al., 2002b]).
Stem cells isolated from the striatum of adult mice and grown in vitro were shown to develop a neuronal phenotype when placed in a proper medium ([Reynolds et al., 1992]). Furthermore, a significant number of newly generated neurons were found to migrate into the striatum from the adjacent SVZ in mice following middle cerebral artery occlusion that causes striatal ischemia ( [Arvidsson et al., 2002 and Parent et al., 2002]). Because the possibility of recruiting new neurons in the adult striatum has profound implications for neurodegenerative diseases that affect the basal ganglia, we used a marker of DNA synthesis that labels proliferating cells (BrdU) to test the hypothesis that new neurons are being produced throughout life in the striatum of normal monkeys ( [Bédard et al., 2002a]). Our data reveal that cells are newly generated in the striatum of normal, adult squirrel monkeys and that a distinct subset of these cells develops a mature neuronal phenotype (NeuN-immunoreactivity) ( Fig. 4E, F). Cells labeled with BrdU were more numerous in the caudate nucleus than in the putamen and more abundant in the dorsomedial than ventrolateral part of both the caudate nucleus and putamen. The number of BrdU-positive cells double labeled for NeuN varied from 2–5/section medially to 1–3/section laterally. Numerous BrdU+ cells appeared in pairs (‘doublets’) and were likely daughter cells of a mitotic event in the striatum. These results suggest that newly generated neurons could come from division of in situ progenitor cells in the striatal parenchyma and/or from migration of SVZ progenitors. These data provide evidence that neurons are newly generated in the striatum of adult normal squirrel monkeys. The morphological and chemical phenotype of these newly generated neurons are currently being characterized, while attempts are made to further increase the number of newborn striatal neurons by using viral vectors encoding various neuronal growth factors ( [Benraiss et al., 2001, Pencea et al., 2001 and Bédard et al., 2002c]).
Concluding remarks
The results of our single-axon tracing studies in both rats and monkeys have revealed that the majority of striatal projection neurons, including those that express SP, are endowed with a highly collateralized axon that allows them to send efferent copies of the same neural information to several striatal targets structures.
Our immunohistochemical investigations in humans have shown that SP-positive fibers arborize in both GPe and GPi, and neurons in these two pallidal segments express NK-1r, the high affinity receptor for SP.
Furthermore, results of calcium-imaging experiments in rat brain slices suggest that pallidal and nigral neurons are both responsive to SP. Altogether, these findings suggest that the functional organization of the striatofugal system is more complex than portrayed in the current model of the basal ganglia.
This model essentially rests upon the segregation of two major populations of striatofugal neurons: (1) the SP-positive neurons that project directly to the GPi/SNr complex through the so-called direct pathway; and (2) the ENK-positive neurons that project exclusively to the GPe and represent the first segment of the so-called indirect pathway.
It has repeatedly been shown that the striatum contains at least two neuronal populations, one expressing ENK and the dopamine receptor D1 and another one expressing SP and the dopamine receptor D2 (see [Aubert et al., 2000]).
However, the link between these two chemospecific neuronal populations and the projection pattern of striatofugal axons described here is unclear. The facts that only 10% of striatal neurons project solely to GPe and that SN contains ENK raise the possibility that a certain proportion of ENK/D2 striatal neurons might project to SN. Furthermore, since all striatonigral neurons project to GPe, there might exist some SP/D1 neurons that act at the pallidal level.
Our data indicate that the axons of striatofugal neurons are much more widely distributed than commonly thought. They also raise the possibility that SP and ENK might be expressed in the same striatofugal neurons but differently conveyed in its various axonal branches and separately release in the different striatal target sites. The striatofugal system stands as an ideal model to study the corelease of different neuroactive peptides, as well as the corelease of GABA, a classic inhibitory transmitter, with a neuroactive peptide.
Up to now, the effect of striatal neurons upon its various target sites has largely been explained through the action of GABA, but more attention should be paid to the effect of SP and ENK that are coreleased with this inhibitory transmitter (see [Maneuf et al., 1994]). The possible role of some SP- or ENK-positive neurons present in extra-striatal structures that project to the striatal target structures, such as the SP-positive neurons present in the dorsal raphe nucleus ( [Baker et al., 1991]), should also be taken into account. More studies are obviously needed to properly assess the influence of striatal neurons on its recipient nuclei.
Our results also point to important differences between rodents and primates in regard to the type of interneurons that prevails at striatal level. Whereas interneurons expressing PV are reportedly the most abundant striatal interneurons in rodents, we found that CR-positive neurons are by far the most plentiful interneurons in the striatum of human and nonhuman primates.
Such a major difference between rodents and primates in the chemical anatomy of the striatum must be taken into account, particularly when interpreting the results obtained in animal models of HD.
Our data also reveal that the neurodegenerative mechanisms at play in HD specifically target the striatal projection neurons, leaving virtually unaltered all types of striatal interneurons. This raises the possibility that the primary pathology in HD might reside in the striatal target structures rather than in the striatum itself. Also worth exploring is the existence of a specific alteration of the corticostriatal pathway that might contribute to the selective vulnerability of striatal medium-sized spiny neurons in HD ([Cepeda et al., 2003]).
Despite their relatively small number, the putative DA neurons intrinsic to the striatum might play a crucial role in the functional organization of this input structure of the basal ganglia, particularly in cases where the striatum is the primary or secondary site of neurodegenerative processes.
Furthermore, we have shown that new neurons are generated on a continuous basis in the striatum of normal adult monkeys, but it is not yet clear if these newborn neurons will eventually developed a DA phenotype and/or will become incorporated into the striatal microcircuitry. Nevertheless, the fact that the number of newborn neurons can be markedly increased following the intraventricular injection of neuronal growth factors raises great hope as to the development of new therapeutic approaches for the treatment of neurodegenerative diseases.
Remarks on second mail to come.
"Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning".
Anne.
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