Morphological, neurochemical, and behavioral studies on serotonergic denervation and graft-induced reinnervation of the rat hippocampus

Luijtelaar, M. G. P. A. van; Tonnaer, J. A. D. M.; Frankhuijzen, A.L.; Dijkstra, H.H.; Hagan, James J.; Steinbusch, H.W.M.

doi:10.1016/0306-4522(91)90381-w

Cited by 17 publications

(5 citation statements)

References 41 publications

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“…This could be especially relevant for the non-specific reduction of NA levels in the parieto-occipital cortex and in the striatum (more severe in the ipsilateral side); however, it probably has no major functional significance, since in order to reduce extracellular NA content, one is required to reduce tissue NA content by greater than 50% (Abercrombie and Zigmond 1989). The more permanent nature of 5,7-DHT lesion (Van Luijtelaar et al 1991) compared to pCA lesion (Sanders-Bush and Steranka 1978) may also partly explain the more profound reduction of 5-HT by 5,7-DHT measured 4 months after administration.…”

Section: Discussionmentioning

confidence: 96%

Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion

et al. 2000

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5-HT system is not essential for the modulation of attention, but it is important in the modulation of response control. Central muscarinic receptors are important in the modulation of attention, whereas central nicotinic receptors may be more essential in response control. The results do not support there being an interaction between the serotonergic and the cholinergic systems in the modulation of attention.

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Section: Discussionmentioning

confidence: 96%

Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion

et al. 2000

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“…Indeed, these immature cells may contribute to a persistent embryonic environment favorable to the development of serotonergic growth cones from all segments, but not to their selection. Thus, serotonergic neurons, which have a high potential for regeneration by collateral sprouting after chemical lesion Zhou et al, 1995) and to innervate the host brain after transplantation of fetal neurons (Daszuta et al, 1991;Rajaofetra et al, 1992;Van Luijtellaar et al, 1991) might be committed, at a very early stage during development, to innervate well-defined targets. This selectivity of serotonergic neurons for specific targets may also persist into adulthood, because we have previously shown that SCO ependymocytes transplanted into the fourth ventricle of adult rats are not innervated by the local supraependymal terminals .…”

Section: Discussionmentioning

confidence: 98%

Specific potentialities of embryonic rat serotonergic neurons to innervate different periventricular targets in the adult brain

et al. 1997

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During the development of the central nervous system, neurons are directed by both genetic and environmental factors to differentiate and form connections with their targets. We took advantage of the abundant homogeneous serotonergic innervations of the ependyma forming the supra- and subependymal plexuses to investigate possible commitment of embryonic neurons to innervate specific targets during axogenesis in the rat. The origin of the supraependymal innervation was determined by retrograde transport of cholera toxin (CT) from the ventricles. The supraependymal plexuses of the fourth ventricle mainly originated from neurons in the dorsocaudal region of the raphe dorsalis (DRN), while the rostral DRN and raphe centralis (CRN) contained perikarya projecting into the third ventricle. This suggested the existence, along the rostrocaudal axis of the raphe, of different neuronal subsets able to form distinct supraependymal plexuses in the third or fourth ventricle. To determine whether serotonergic neurons were committed to innervate specific areas of the ependyma, different embryonic metencephalic segments (rostral, median, or caudal) from 14-day-old rat embryos were independently grafted into the third or fourth ventricle of an adult brain in which the serotonergic neurons had been previously destroyed. The distinctive patterns of re-innervation specific to each of grafted segments indicate that subsets of embryonic serotonergic neurons are indeed committed to innervate certain restricted ependymal areas of the adult brain, presumably in response to different neurotropic and/or neurotrophic cues.

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“…In fact, previous studies have shown that the amplitude of the graft‐induced neurochemical effects decreases when the distance from the graft increases (e.g. Van Luijtelaar et al ., 1991; Cassel et al ., 1993; Jeltsch et al ., 1994). Concerning the accumulation of 5‐HT and its release, the weaker responsiveness of the grafts is probably due to the smaller number of cells injected (about half the amount used by Balse et al ., 1999).…”

Section: Discussionmentioning

confidence: 99%

5,7‐dihydroxytryptamine lesions enhance and serotonergic grafts normalize the evoked overflow of acetylcholine in rat hippocampal slices

Birthelmer¹,

Schweizer²,

Jeltsch³

et al. 2002

Eur J of Neuroscience

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Adult rats were subjected to intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT; 150 micro g) and, 15 days later, to intrahippocampal grafts of fetal raphe cell suspensions. About 11 months later, we assessed baseline and electrically evoked release of tritium ([3H]) in hippocampal slices, preloaded with tritiated ([3H])choline or [3H]serotonin (5-HT), in the presence or absence of the 5-HT1B receptor agonist CP-93,129 and the 5-HT receptor antagonist methiothepine. HPLC determinations of monoamine concentrations were also performed. The lesions reduced the concentration of 5-HT (-90%) and the accumulation (-80%) as well as the evoked release (-90%) of [3H]5-HT. They also decreased the inhibitory effects of CP-93,129 on the evoked release of [3H]5-HT. Most interestingly, they facilitated the evoked release of [3H]acetylcholine (+20%). In slices from rats subjected to lesions and grafts, the responsiveness of the serotonergic autoreceptors (presumably located on the terminals of the grafted neurons) and the release of acetylcholine were close to normal. These results confirm that grafts rich in serotonergic neurons may partially compensate for the dramatic effects of 5,7-DHT lesions on serotonergic hippocampal functions. The lesion-induced reduction of the 5-HT1B autoreceptor-mediated inhibition of evoked 5-HT release may be an adaptation enhancing serotonergic transmission in the (few) remaining terminals. The facilitated release of acetylcholine is probably caused by a reduced serotonergic tone on the inhibitory 5-HT1B heteroreceptors of the cholinergic terminals. When related to data in the literature, this facilitation may be of particular interest in terms of transmitter-based strategies developed to tackle cognitive symptoms related to neurodegenerative diseases.

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Morphological, neurochemical, and behavioral studies on serotonergic denervation and graft-induced reinnervation of the rat hippocampus

Cited by 17 publications

References 41 publications

Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion

Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion

Specific potentialities of embryonic rat serotonergic neurons to innervate different periventricular targets in the adult brain

5,7‐dihydroxytryptamine lesions enhance and serotonergic grafts normalize the evoked overflow of acetylcholine in rat hippocampal slices

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