Homologous cholinergic efferents spared by partial fimbrial lesions contribute to the recovery of hippocampal cholinergic enzymes in adult rats

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

doi:10.1016/0006-8993(86)91621-5

Cited by 22 publications

(2 citation statements)

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“…When either the fimbria is cut or electrolytic lesions of the medial septum are made in rodents, ChAT activity levels decline precipitously in the hippocampus within days /17, 152,154,163,164,203,362,464,465,484/, and the same occurs in the rodent cortex following lesions of the nbM /57, 108,192,193,220,401,465/. However, NGF injections have been shown to increase the number, size, and signal intensity of ChAT-positive and NGF receptor-positive neurons in the adult rodent basal forebrain /218/ and striatum /151/.…”

Section: Effects On Cholinergic Basal Forebrain Neuronsmentioning

confidence: 99%

Nerve Growth Factor and Alzheimer's Disease

Scott¹,

Crutcher²

1994

Reviews in the Neurosciences

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Nerve growth factor (NGF) is a well-characterized protein that exerts pharmacological effects on a group of cholinergic neurons known to atrophy in Alzheimer's disease (AD). Considerable evidence from animal studies suggests that NGF may be useful in reversing, halting, or at least slowing the progression of AD-related cholinergic basal forebrain atrophy, perhaps even attenuating the cognitive deficit associated with the disorder. However, many questions remain concerning the role of NGF in AD. Levels of the low-affinity receptor for NGF appear to be at least stable in AD basal forebrain, and the recent finding of AD-related increases in cortical NGF brings into question whether endogenous NGF levels are related to the observed cholinergic atrophy and whether additional NGF will be useful in treating this disorder. Evidence regarding the localization of NGF within the central nervous system and its presumed role in maintaining basal forebrain cholinergic neurons is summarized, followed by a synopsis of the relevant aspects of AD neuropathology. The available data regarding levels of NGF and its receptor in the AD brain, as well as potential roles for NGF in the pathogenesis and treatment of AD, are also reviewed. NGF and its low affinity receptor are abundantly present within the AD brain, although this does not rule out an NGF-related mechanism in the degeneration of basal forebrain neurons, nor does it eliminate the possibility that exogenous NGF may be successfully used to treat AD. Further studies of the degree and distribution of NGF within the human brain in normal aging and in AD, and of the possible relationship between target NGF levels and the status of basal forebrain neurons in vivo, are necessary before engaging in clinical trials.

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Section: Effects On Cholinergic Basal Forebrain Neuronsmentioning

confidence: 99%

Nerve Growth Factor and Alzheimer's Disease

Scott¹,

Crutcher²

1994

Reviews in the Neurosciences

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“…One possible explanation for this recovery of function is that, with time, the hippocampal formation reestablishes its cholinergic innervation via sprouting by residual fibers that enter through the ventral cholinergic bundle. The cholinergic reinnervation of the fornixtransected hippocampus in the rat appears to be a robust phenomenon (Gage et al, 1983(Gage et al, , 1984Dravid and Van Deusen, 1984;Gasser et al, 1986;Blaker et al, 1988;Batchelor et al, 1989;He et al, 1991). In the rat, the process of sprouting is relatively fast.…”

Section: Functional Considerationsmentioning

confidence: 99%

Cholinergic innervation of the primate hippocampal formation: II. Effects of fimbria/fornix transection

Alonso

Amaral

1996

J. Comp. Neurol.

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The distribution of choline acetyltransferase (ChAT)-immunoreactive and acetylcholinesterase (AChE)-positive fibers and terminals was analyzed in the hippocampal formation of macaque monkeys subjected to transection of the fimbria/fornix. Cases with either unilateral or bilateral transections were prepared, with post transection survival times ranging from 2 weeks to 1.5 years. The fimbria/fornix transection resulted in a dramatic decrease in the number of cholinergic fibers in most regions of the hippocampal formation. Some hippocampal regions, however, showed relatively greater sparing of ChAT- or AChE-positive fibers. In practically all regions of the hippocampal formation, residual AChE-positive fibers were more abundant than ChAT-immunoreactive fibers. In animals with unilateral lesions, the distribution patterns and density of AChE and ChAT staining on the side contralateral to the lesion were generally similar to those of sections from unlesioned control brains. The largest decreases in the densities of positive fibers were observed in the dentate gyrus, CA3 and CA2 fields of the hippocampus, subiculum, parasubiculum, and medial and caudal parts of the entorhinal cortex. Fibers were relatively better preserved in the rostral or uncal portion of the hippocampus and dentate gyrus and in the rostral portion of the entorhinal cortex. The presubiculum demonstrated remarkable sparing that contrasted with the almost complete loss of fibers in the parasubiculum. Interestingly, animals killed approximately 1.5 years after the fornix transection showed essentially the same pattern of fiber loss as the cases with shorter survival periods. This indicates that the residual ChAT-immunoreactive fibers, many of which reach the hippocampal formation through a ventral cholinergic pathway, are not capable of reinnervating the denervated portions of the hippocampal formation. This appears to distinguish the monkey from the rat, for which substantial sprouting and reinnervation of cholinergic fibers have been reported after similar lesions.

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