Biomedical subjects

H Jeltsch

Publications and source records attributed to H Jeltsch.

25 records · Page 2Linked to original sources

PubMed1995

Serotonergic modulation of cholinergic function in the central nervous system: cognitive implications.

Accumulating evidence suggests that serotonin may modulate cholinergic function in several regions of the mammalian brain and that these serotonergic/cholinergic interactions influence cognition. The first part of this review is an overview of histological, electrophysiological and pharmacological (in vitro, in vivo) data indicating that, in several brain regions (e.g., hippocampus, cortex and striatum), there are neuroanatomical substrates for a serotonergic/cholinergic interaction, and that alterations in serotonergic activity may induce functional changes in cholinergic neurons. In the second part, the review focuses on experimental approaches showing or suggesting that central cholinergic and serotonergic mechanisms are cooperating in the regulation of cognitive functions. These arguments are based on lesion, intracerebral grafting and pharmacological techniques. It is concluded that not all mnesic perturbations induced by concurrent manipulations of the serotonergic and cholinergic systems can be attributed to a serotonergic modification of the cholinergic system. The cognitive faculties of an organism arise from interactions among several neurotransmitter systems within brain structures such as, for instance, the hippocampus or the cortex, but also from influences on memory of other general functions that may involve cerebral substrates different from those classically related to mnesic functions (e.g., attention, arousal, sensory accuracy, etc.).

Animals↗

PubMed1995

Sympathetic sprouting: time course of changes of noradrenergic, cholinergic, and serotonergic markers in the denervated rat hippocampus.

As a first step for experiments investigating the presynaptic characteristics of sympathetic fibers grown into the denervated hippocampus, we studied the time course of changes of neurochemical markers in the rat hippocampus, subsequent to aspiration lesions of the fimbria-fornix and the overlying callosal and cortical structures. At various postsurgical delays (1, 2, 8, 24, and 40 weeks), the activity of choline acetyltransferase, the high-affinity synaptosomal uptake of choline and noradrenaline, and the concentrations of noradrenaline, serotonin, and 5-hydroxyindoleacetic acid were measured in a dorsal, an intermediate, and a ventral part of the hippocampus. Levels of all markers were significantly reduced shortly (1-2 weeks) after the lesions. However, whereas the cholinergic (choline uptake and choline acetyltransferase activity) and the serotonergic (concentrations of serotonin and 5-hydroxyindoleacetic acid) markers remained significantly reduced for up to 40 weeks, both noradrenergic markers recovered to near-normal (noradrenaline uptake) or even supranormal (noradrenaline concentration) levels, although with clear-cut differences in the time course and the regional characteristics. The noradrenaline content reached control levels already 8 weeks after lesion surgery and was about two to three times higher 40 weeks later, with the most dramatic effects in the ventral hippocampus. In contrast, high-affinity noradrenaline uptake reached control values only 24 weeks after lesion and exceeded them only in the ventral hippocampus 40 weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The effects of intrahippocampal raphe and/or septal grafts in rats with fimbria-fornix lesions depend on the origin of the grafted tissue and the behavioural task used.

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, two weeks later, received intrahippocampal suspension grafts of fetal tissue. The grafts were prepared from regions including either the medial septum and the diagonal band of Broca (septal grafts), or the mesencephalic raphe (raphe grafts), or from both these regions together (co-grafts). All rats were submitted to a series of behavioural tests (home cage and open-field locomotion, spontaneous alternation, radial-arm maze and Morris water maze performance) run over two periods after grafting (one to nine weeks and 20-35 weeks). Two weeks after completion of behavioural testing, histological (acetylcholinesterase and Cresyl Violet staining) and/or neurochemical (choline acetyltransferase activity, high-affinity synaptosomal uptake of choline and serotonin, noradrenaline, serotonin and 5-hydroxyindolacetic acid concentrations) verifications were performed on the hippocampus. Compared to sham-operated rats, lesion-only rats exhibited hyperactivity which was transient in a familiar environment (home cage) and lasting in an unfamiliar one (open field), decreased rates of spontaneous T-maze alternation, and impaired memory performance in both the radial-arm maze and the Morris water maze. These rats also showed decreased cholinergic and serotonergic markers with a maximal depletion in the septal two-thirds of the hippocampus. Noradrenaline concentration tended to be increased in the dorsal third of the hippocampus, but was not modified in the other two-thirds. While septal grafts specifically increased the cholinergic markers and raphe grafts the serotonergic ones, neither of these grafts produced a lasting effect on any behavioural variable. Conversely, the co-grafts, which increased both the cholinergic and serotonergic markers in the septal two-thirds of the hippocampus, completely normalized the Morris water maze probe trial performance, but failed to affect any of the other behavioural variables. Our present results confirm that grafts of fetal neurons injected into the denervated hippocampus may induce a neurochemical recovery that depends on the anatomical origin of the grafted cells, and that co-grafting two fetal brain regions allows the combination of their individual neurochemical properties. Furthermore, our results show that these neurochemical effects of the co-grafts may be involved in the recovery of behavioural function observed in the water maze. However, somewhat paradoxically, those effects appear inefficient for inducing any recovery in other behavioural tasks, even in the radial-arm maze; which is assumed to measure similar spatial functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Hippocampal amino acid concentrations after raphe and/or septal cell suspension grafts in rats with fimbria-fornix lesions.

Two weeks after infracallosal electrolytic fimbria-fornix lesions, Long-Evans female rats received intrahippocampal suspension grafts of either fetal septal or mesencephalic raphe tissue, or a mixture of both. Ten months after lesion surgery, the concentrations of alanine, aspartate, GABA, glutamate, glutamine, glycine, serine and taurine were determined in a dorsal, a "middle" and a ventral region of the hippocampus. We found neither the lesions nor the grafts to have significantly modified the concentration of these amino acids which, in all groups, presented a regional heterogeneity in their hippocampal distribution. GABA, glutamate and glutamine were highest in the ventral hippocampus, whereas the other amino acids were highest in the dorsal region. Our results (i) show that fimbria-fornix lesions do not result in lasting effects on hippocampal concentrations of the assessed amino acids, (ii) confirm the regional heterogeneity in the distribution of these amino acids in the hippocampus and (iii) demonstrate that cell suspension grafts of fetal septal or mesencephalic raphe tissue, as well as grafts of a mixture of both of these tissues, do not exert a non-specific effect on either of the amino acid concentrations measured. These data complete those of the preceeding paper [Kiss et al. (1990) Neuroscience 36, 61-72] concerning the effects of the same grafts on hippocampal cholinergic, serotonergic and noradrenergic markers, as well as on several behavioural variables.

Amino Acids↗

PubMed1994

Lesions of supracallosal or infracallosal hippocampal pathways in the rat: behavioral, neurochemical, and histochemical effects.

Long-term behavioral and neurochemical effects of bilateral lesions to only the infracallosal component of the "so-called" septohippocampal pathways (cingular bundle, fimbria and fornix) have not been assessed. This experiment compared the behavioral, histochemical and neurochemical effects of supracallosal (SUPRA; cingular bundle) and infracallosal (INFRA; fimbria-fornix) hippocampal denervations in Long-Evans female rats. The rats were tested, over two periods (8-52 and 92-170 days postlesion), for open field locomotion, spontaneous alternation and radial-maze performance. Subsequently, histochemical or neurochemical determinations of cholinergic, serotonergic and noradrenergic hippocampal innervations were performed using acetylcholinesterase-staining, determination of high-affinity synaptosomal uptake of choline and serotonin, and measurement of hippocampal serotonin and noradrenaline concentrations by HPLC methods. Whatever behavioral test was considered, no significant effect was found in rats with SUPRA lesions, whereas rats with INFRA lesions were permanently impaired in all tests. Histochemical and neurochemical analyses showed hippocampal cholinergic as well as serotonergic markers to be substantially decreased in INFRA rats as compared to SHAM and SUPRA rats. The SUPRA rats exhibited a weak but significant reduction of both serotonergic and noradrenergic markers compared to SHAM and INFRA rats. These results suggest that lesions limited to the infracallosal pathway induce a hippocampal denervation sufficient to account for most of the behavioral, histochemical and neurochemical deficits classically reported following extensive lesions of the anterior hippocampal connections. Since the behavioral and neurochemical deficits were found to be lasting, it is suggested that bilateral infracallosal damage to the septohippocampal pathways might constitute an interesting paradigm of partial hippocampal deafferentation to investigate the effects of neural grafts or other treatments in an animal model of Alzheimer's disease.

Acetylcholinesterase↗

PubMed1994

Differential behavioral effects of supracallosal and infracallosal lesions of the septohippocampal pathways: no ameliorative effects of oxotremorine or pilocarpine on radial-maze performance.

We examined the effects in young adult female Long-Evans rats of single or combined lesions of the infracallosal and supracallosal septohippocampal pathways on a battery of behavioral tasks over two postoperative periods (14-65 and 75-150 days, respectively). During the first period, rats with lesions of the infracallosal pathways, whether given alone or in combination with lesions of the supracallosal pathways, were more active in the open field and in their home cage, and showed increased reactivity to novel extracage stimuli. Behavioral results during the second postoperative period were similar to those of the first except that rats with lesions of the infracallosal pathways (either alone or in combination with lesions of the supracallosal pathways) were no longer hyperactive in their home cage and rats with the infracallosal lesion alone were no longer hyperactive in the open field. We also observed in rats with lesions of the infracallosal pathways impaired performance in the radial-arm maze task, whether conducted under an uninterrupted protocol (first and second postoperative periods) or with a 1-min intratrial interruption (second postoperative period). Thus, behavioral deficits were observed only in rats with a lesion to the infracallosal component of the septohippocampal pathways, the behavior of rats with the combined lesions being similar to that of rats with single lesions of the infracallosal pathways in most measures. The behavior of rats with lesions of the supracallosal pathways did not differ from that of sham-operated controls in any measure at either postoperative period. Acute, systemic injections of oxotremorine (0.03 or 0.1 mg/kg, ip) or pilocarpine (0.32 or 1.0 mg/kg, ip), two muscarinic agonists, did not affect radial-arm maze performance under either the uninterrupted or interrupted protocol. The use of nonspecific muscarinic agonists does not appear to be sufficient to enhance radial-arm maze performance in rats with infracallosal septohippocampal lesions which, in contrast to supracallosal lesions, were shown to induce a deficit in this task.

Afferent Pathways↗

PubMed1993

Effects of grafts containing cholinergic and/or serotonergic neurons on cholinergic, serotonergic and noradrenergic markers in the denervated rat hippocampus.

Long-Evans female rats sustained aspirative lesions of the septohippocampal pathways and, 2 weeks later, received intrahippocampal suspension grafts prepared from the regions including either the medial septum and the diagonal band of Broca (group S), or the mesencephalic raphe (group R), or from both these regions together (group S + R). Sham-operated (group SHAM) and lesion-only (group LES) rats were used as controls. Six months after grafting, high affinity synaptosomal uptake of choline (HACU) and serotonin (HASU), choline acetyltransferase (ChAT) activity and, using HPLC, the content of serotonin ([5-HT]), 5-hydroxyindolacetic acid ([5-HIAA]) and noradrenaline ([NA]) were determined in three rostro-caudal segments of the hippocampus (designated hereafter as the dorsal, the 'middle' and the ventral segments). In all three segments of the dorsal hippocampus, septohippocampal lesions decreased HACU, ChAT activity, HASU and [5-HT]; [5-HIAA] was decreased only in the middle and ventral hippocampal segments. The lesions also resulted in an above normal increase of [NA]. Septal grafts increased HACU and ChAT in the three hippocampal regions, had no effect on serotonergic markers and attenuated the lesion-induced increase of [NA] in only the dorsal and middle hippocampal segments. Raphe grafts increased HASU, [5-HT] and [5-HIAA] in the dorsal and middle hippocampal segments, had no effects on cholinergic markers and did not affect the lesion-induced increase of [NA]. Co-grafts increased HACU, ChAT activity, HASU, [5-HT] and [5-HIAA], and attenuated the lesion-induced increase in [NA]. These data demonstrate that grafts of fetal neurons placed into the denervated hippocampus may induce a neurochemical recovery which depends upon the anatomical origin of the grafted cells. They also show that co-grafting allows to combine the neurochemical properties of two fetal brain regions grafted separately. Furthermore, our findings suggest that graft-derived cholinergic reinnervation of the hippocampus prevents the lesion-induced increase of noradrenaline concentration which is likely to result from sympathetic sprouting. Thus, our data confirm the results of a previous experiment carried out at a post-grafting delay of 10-11 months, and show that the graft-induced effects reported previously are already massively present by 6 months after surgery.

Analysis of Variance↗