Impaired spatial learning in aged rats is associated with loss of p75-positive neurons in the basal forebrain

Greferath, Ursula; Bennie, Antoinette; Kourakis, Angela; Barrett, Graham L.

doi:10.1016/s0306-4522(00)00260-8

Cited by 36 publications

(42 citation statements)

References 46 publications

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“…With respect to the effects of aging, it is well documented that cholinergic deficiency occurs late in life and the condition of basal forebrain cholinergic neurons has been correlated with cognitive impairment (for reviews, see Gallagher et al, 1990;Gill and Gallagher, 1998;Greferath et al, 2000;Stemmelin et al, 2000). The current findings, as well as other research (Baxter et al, 1995, indicate that selective elimination of the basal forebrain cholinergic system in young rats is not sufficient to reproduce the profile of behavioral impairment associated with aging.…”

Section: Discussionmentioning

confidence: 54%

Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze

et al. 2003

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Recent evidence has suggested that the relative levels of acetylcholine (ACh) between brain structures may be an important factor in the choice of behavioral strategy in settings in which either hippocampal or dorsal striatal brain systems can be employed both effectively and independently (McIntyre and Gold. 1999. Soc Neurosci Abs 25:1388). The current investigation used the neurotoxin 192 IgG-saporin to deplete the hippocampus of ACh selectively, while leaving ACh in other brain regions, including dorsal striatum, intact. Rats were then trained on a version of the Morris water maze, in which behavioral strategies attributed to the hippocampus and dorsal striatum are placed in direct competition. It was predicted that rats with hippocampal ACh depletion would display a cue bias. Contrary to this prediction, depleting hippocampal ACh did not bias against and, in fact, promoted use of a hippocampal place strategy in this task, as indicated by choice in competition tests and performance on hidden platform training trials. These data add to a growing literature demonstrating that the septohippocampal cholinergic system is not required for accurate spatial learning and suggest a complex role for basal forebrain projections in processing information about the spatial environment.

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Section: Discussionmentioning

confidence: 54%

Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze

et al. 2003

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“…We have previously demonstrated that the NGF signal can reach the basal forebrain within 15 minutes of a hippocampal injection, despite pretreatment with a microtubule inhibitor, colchicine [44]. In the present study, given the distance the signal must travel, and the known rate of microtubule transport [18], we therefore believe that this one-hour signal is communicated to the basal forebrain largely by microtubule-independent signaling of activated second messengers possibly similar to mechanisms that exist for the rapid signaling of other trophic factors such as EGF [43]. Our data strongly support that such a rapid signaling cascade exists for NGF in the central nervous system (CNS).…”

Section: Ngf Signaling In the Cnsmentioning

confidence: 55%

Age-dependent loss of NGF signaling in the rat basal forebrain is due to disrupted MAPK activation

Williams

Granholm

Sambamurti

2007

Neuroscience Letters

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The loss of Nerve Growth Factor (NGF) and its high affinity receptor TrkA has been implicated in the loss of cholinergic tone and function in Alzheimer's disease (AD) and normal aging. We employed an animal model of aging, the aged rat, which also exhibits memory loss and NGF alterations. Basal forebrain TrkA levels increased after injection of NGF in the hippocampus within one-hour in young rats, but this response was diminished in aged animals as determined by Western blot analysis. Further, NGF activated MAPK pathways without changing total ERK levels and the activation of these pathways was also diminished in aged animals. The exogenous NGF injection did not appear to activate the PI-3K pathway or alter total levels of Akt significantly. These data shed light on mechanisms of NGF signaling in the CNS, and alterations in this signaling cascade associated with age and memory loss. These findings might lead to development of novel treatment therapies for the memory loss associated with AD and other age-associated neurodegenerative diseases.

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“…There is known to be a high degree of correspondence between p75 NTR and ChAT immunoreactivity in basal forebrain neurons in rats (Kiss et al, 1988;Pioro and Cuello, 1990;Greferath et al, 2000a), so these were essentially cholinergic neurons. There were no statisti- cally significant intergroup differences in cell soma size in the MS/VDB.…”

Section: Neuronal Sizementioning

confidence: 99%

“…Spatial learning ability was tested by using the Barnes circular maze (Barnes, 1979), modified as previously described (Greferath et al, 2000a). The Barnes maze consisted of a white circular platform (1.2 m diameter), standing 0.9 m above floor level, with 18 holes spaced around the periphery.…”

Section: Barnes Circular Mazementioning

confidence: 99%

“…The ChAT-immunopositive basal forebrain neurons are also p75 NTR immunopositive (Hefti et al, 1986;Greferath et al, 2000a), and there is considerable evidence that p75 NTR has an antitrophic role and can down-regulate ChAT expression (Yeo et al, 1997;Greferath et al, 2000b;Zagrebelsky et al, 2005). We have previously shown that estradiol treatment reduces the expression of p75 NTR in the basal forebrain in old rats (Ping et al, 2002).…”

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confidence: 94%

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Effects of estrogen on basal forebrain cholinergic neurons and spatial learning

Ping

Trieu

Wlodek

et al. 2008

J of Neuroscience Research

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Estrogen receptors are expressed in several areas of the brain associated with cognition, including the basal forebrain cholinergic nuclei, and numerous reports have described improvements in memory in response to estrogen supplementation. The relationship between estrogen's effects on the basal cholinergic system and improvements in cognitive function, however, are obscure. We therefore undertook a study to determine the effects of estrogen on several parameters of the cholinergic system in ovariectomized rats and measured the concomitant effects on performance in the Barnes maze, a test of spatial memory. Six weeks of estradiol treatment caused an increase in choline acetyltransferase activity throughout the projection fields of the basal forebrain, including the hippocampal formation (14%), olfactory bulb (30%), and cerebral cortex (35%). Estrogen treatment also caused an increase in cell soma size of cholinergic neurons in the horizontal diagonal limb of the band of Broca and in the basal nucleus of Meynert. There was no change in the number of neurons positive for p75(NTR), nor in the level of p75(NTR) expression per neuron. Barnes maze performance was markedly improved after estradiol treatment, reinforcing the view that estrogen has beneficial cognitive effects, particularly on spatial memory. The beneficial cognitive effect was likely mediated in part by stimulation of the basal forebrain cholinergic system, especially in its neocortical projection, but was not associated with changes in the level of p75(NTR) expression.

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Impaired spatial learning in aged rats is associated with loss of p75-positive neurons in the basal forebrain

Cited by 36 publications

References 46 publications

Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze

Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze

Age-dependent loss of NGF signaling in the rat basal forebrain is due to disrupted MAPK activation

Effects of estrogen on basal forebrain cholinergic neurons and spatial learning

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