Recovery of enzyme markers for cholinergic terminals in septo-temporal regions of the hippocampus following selective fimbrial lesions in adult rats

Dravid, A. R.; Deusen, E.B. Van

doi:10.1016/0006-8993(84)90628-0

Cited by 57 publications

(9 citation statements)

References 33 publications

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“…In line with this, injection of a second retrograde tracer (Fast Blue) into the hippocampus 6 months after axotomy did not reveal retrogradely labeled neurons in the MS (Naumann et al, 1992b). Certainly, this does not exclude sprouting of cholinergic fibers traversing through the ventral route (Gage et al, 1983;Dravid and van Deusen, 1984;Milner and h aral, 1984). In the present experiments, animals with substantial AChE fiber staining were not included, since it appeared difficult to decide whether the staining was due to an incomplete lesion or sprouting.…”

Section: Discussionmentioning

confidence: 88%

“…For this, sections from different septotemporal levels of the hippocampus were analyzed. We regard this control as a strict criterion and are aware that some animals were discarded this way that had complete lesions but showed sprouting of cholinergic fibers reaching the hippocampus via the ventral route (Gage et al, 1983;Dravid and van Deusen, 1984;Milner and Amaral, 1984).…”

Section: Chat Immunocytochemistrymentioning

confidence: 99%

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Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria‐fornix transection

Naumann

Kermer

Frotscher

1994

J of Comparative Neurology

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Most cholinergic projection neurons in the medial septal nucleus (MS) lose their capability to synthesize choline acetyltransferase (ChAT) after axotomy by bilateral fimbria-fornix transection. We have recently shown that identified septohippocampal neurons survive axotomy up to 10 weeks and display fine-structural characteristics of cells in control rats. However, the fate and functional role of these neurons remained unclear. Here we describe observations made in rats which survived axotomy for 6 months. Adult Sprague-Dawley rats were subjected to bilateral transection of the fimbria-fornix system. In some animals septohippocampal projection neurons were labeled by the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy. After varying survival times following fimbria-fornix transection, the animals were fixed and sections of the septal region immunostained for ChAT. Three weeks postlesion, the number of ChAT-positive cells in the MS was reduced to 19% of control, suggesting a severe neuronal loss. However, 10 weeks and 6 months after axotomy this value increased to 28% and 54%, respectively. Fine-structural analysis of ChAT-positive neurons after 6 months survival revealed all characteristics of vital cells including normal input synapses. The majority of these cells could be identified as former septohippocampal projection neurons by the presence of FG. We conclude that many neurons in the MS have the capacity to restore their transmitter synthesis in a long-lasting process following axotomy.

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Section: Discussionmentioning

confidence: 88%

Section: Chat Immunocytochemistrymentioning

confidence: 99%

Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria‐fornix transection

Naumann

Kermer

Frotscher

1994

J of Comparative Neurology

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“…Such compensatory changes may involve increases in enzyme activity in remaining terminals, and/or compensatory sprouting of remaining axons in response to an ongoing degenerative process. Previous studies in young adult rats (Oderfeld-Novak et al, 1977;Gage et al, 1983a, b;Dravid and Van Deusen, 1984) have shown that partial cholinergic deafferentation of the hippocampal formation is at least partially compensated for by a protracted collateral sprouting from the spared cholinergic afferents, which can restore hippocampal ChAT levels. Indeed, Hoff et al (1982) have shown that the capacity for lesion-induced sprouting is retained also in aged rats.…”

Section: Discussionmentioning

confidence: 96%

Degenerative Changes in Forebrain Cholinergic Nuclei Correlate with Cognitive Impairments in Aged Rats

Fischer

Gage

Björklund

1989

Eur J of Neuroscience

327

104

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Degenerative changes in the forebrain cholinergic nuclei have been studied morphometrically in behaviourally characterized aged female Sprague-Dawley rats. In all regions analysed (medial septum, diagonal band of Broca, nucleus basalis, and striatum) the acetylcholinesterase-positive neurons were reduced in both size and number in the aged (24-months-old) rats as compared to the young (3-months-old) controls. The overall reduction in cell size amounted to between 20 and 30% and the overall reduction in cell number to between 27 and 45%. Impairment in learning and/or memory performance in the aged rats, as assessed in the Morris' water-maze task, was significantly correlated with both cholinergic cell size and cell number in the medial septum, and with cholinergic cell number in the diagonal band of Broca and in the striatum. In the nucleus basalis there was a trend in the same direction but it did not reach significance. In contrast to these degenerative changes in the cell body regions, no significant differences in cortical or hippocampal choline acetyltransferase activity were detected biochemically between the young and the aged rats, and the enzyme activity levels did not correlate with the degree of behavioural impairment in the aged rats. The present results provide evidence that all major forebrain cholinergic cell groups undergo degenerative changes with age in the rat, and that the most severe changes are found in those rats which display the most profound spatial learning impairments. Despite the severe changes at the cell body level, however, the choline acetyltransferase activity in the cortical projection areas are affected only to a minor degree, perhaps as a result of functional compensatory changes at the terminal level.

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“…The persistence of reduced AChE levels in spite of the ALCAR treatment might indicate the necessity of a longer treatment in order for AChE activity to be recovered, or longer time intervals after lesion. 9 The neuroprotective action of ALCAR on aged CNS neurons has been extensively demon° strated, 32 We have previously shown that a long ALCAR treatment attenuates the reduction of ChAT activity in the septal cholinergic neurons of total fimbria-fornix lesioned adult rats, 39 as well as of aged rats. 47 The capacity of ALCAR to enhance the neurotrophic action of NGF in lesioned rats might be hypothesized; consistently with this hypothesis, a similar NGF-stimulating activity of ALCAR has been shown in vitro on rat pheocromocytoma PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

Acetyl‐l‐carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria‐fornix transection

Piovesan

Quatrini

Pacifici

et al. 1995

Intl J of Devlp Neuroscience

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Transection of the fimbria-fornix bundle in adult rats results in degeneration of the septohippocampal cholinergic pathway, reminiscent of that occurring in aging as well as Alzheimer disease. We report here a study of the effect of a treatment with acetyl-L-carnitine (ALCAR) in three-month-old Fischer 344 rats bearing a partial unilateral fimbria-fornix transection. ALCAR is known to ameliorate some morphological and functional disturbances in the aged central nervous system (CNS). We used choline acetyltransferase (ChAT) and acetyl cholinesterase (AChE) as markers of central cholinergic function, and nerve growth factor (NGF) levels as indicative of the trophic regulation of the medio-septal cholinergic system. ChAT and AChE activities were significantly reduced in the hippocampus (HIPP) ipsilateral to the lesion as compared to the contralateral one, while no changes were observed in the septum (SPT), nucleus basalis magnocellularis (NBM) or frontal cortex (FCX). ALCAR treatment restored ChAT activity in the ipsilateral HIPP, while AChE levels were not different from those of untreated animals, and did not affect NGF content in either SPT or HIPP.

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Recovery of enzyme markers for cholinergic terminals in septo-temporal regions of the hippocampus following selective fimbrial lesions in adult rats

Cited by 57 publications

References 33 publications

Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria‐fornix transection

Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria‐fornix transection

Degenerative Changes in Forebrain Cholinergic Nuclei Correlate with Cognitive Impairments in Aged Rats

Acetyl‐l‐carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria‐fornix transection

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