Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies

Auld, Daniel; Kornecook, Tom J.; Bastianetto, Stéphane; Quirion, Rémi

doi:10.1016/s0301-0082(02)00079-5

Cited by 615 publications

(409 citation statements)

References 470 publications

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“…The earliest pathological events in Alzheimer's disease are thought to be the degeneration of basal forebrain cholinergic neurons, whose severity could positively correlate with memory impairments (Auld et al, 2002;Schliebs and Arendt, 2011). This finding has led to pro-cognitive therapeutic strategies via acetylcholine (ACh) neurotransmission, either by enhancing its endogenous level, or by reducing the activity of cholihttp://dx.doi.org/10.1016/j.neuroscience.2017.04.011 0306-4522/Ó 2017 IBRO.…”

Section: Introductionmentioning

confidence: 99%

Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a streptozotocin model of Alzheimer’s disease

et al. 2017

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Abstract-Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv-STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway. Rats treated with icv-STZ were submitted to a chronic Nic regime, and were evaluated for recognition memory. We then examined long-term potentiation (LTP), paired-pulse facilitation (PPF) under urethane anesthesia, and brains were also evaluated for hippocampus-mPFC cell density. We found that Nic treatment prevents icv-STZ-induced disruptions in recognition memory and LTP. STZ did not precipitate neuronal death, while Nic alone was associated with higher neuronal density in CA1 when compared to vehicle-injected animals. Through combining behavioral, neurophysiological, and neuropathological observations into the Nic-STZ interplay, our study reinforces that cholinergic treatments are of clinical importance against earlystage Alzheimer's disease and mild cognitive impairments.

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Section: Introductionmentioning

confidence: 99%

Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a streptozotocin model of Alzheimer’s disease

et al. 2017

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“…Cholinergic function is considered to be vital in attention, memory and other cognitive processing (Everitt and Robbins, 1997;Sarter et al, 2005). Cholinergic neuronal pathology, as found in Alzheimer's disease, is accompanied by cognitive and behavioral deficits (Whitehouse et al, 1981;Guela and Mesulam, 1994;Bartus, 2000;Auld et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

Leung

Petropoulos

Shen

et al. 2011

Experimental Neurology

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"Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics" (2011). Physiology and Pharmacology Publications. 72. https://ir.lib.uwo.ca/physpharmpub/72 This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Acetylcholine in the brain has been associated with consciousness and general anesthesia effects. We tested the hypothesis that the integrity of the nucleus basalis magnocellularis (NBM) affects the response to general anesthetics. Cholinergic neurons in NBM were selectively lesioned by bilateral infusion of 192IgG-saporin in adult, male Long-Evans rats, and control rats were infused with saline. Depletion of choline-acetyltransferase (ChAT)-immunoreactive cells in the NBM and decrease in optical density of acetylcholinesterase (AChE) staining in the frontal and visual cortices confirmed a significant decrease in NBM cholinergic neurons in lesioned as compared to control rats. AChE staining in the hippocampus and ChAT-positive neurons in the medial septum-vertical limb of the diagonal band were not different between lesioned and control rats. When a general anesthetic was administered, lesioned compared to control rats showed significantly longer duration of loss of righting reflex (LORR) after propofol (5 or 10 mg/kg i.v.), pentobarbital (20 or 40 mg/kg i.p.) but not halothane (2%). However, the behavioral excitation, as indicated by horizontal movements, induced by halothane was reduced in lesioned as compared to control rats. Reversible inactivation of NBM with GABA A receptor agonist muscimol increased slow waves in the neocortex during awake immobility, and prolonged the duration of LORR and loss of tail-pinch response after propofol, pentobarbital and halothane. In summary, lesion of NBM cholinergic neurons or inactivation of the NBM prolonged the LORR response to general anesthetic drugs.

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“…Interactions between these two neurotransmitter systems play key roles in learning and memory (Levin et al, 1990) and these systems, particularly the cholinergic innervation, are severely affected in Alzheimer's Disease (Araujo et al, 1988;Auld et al, 2002;Davies and Maloney, 1976;Perry et al, 1992). Hippocampal cholinergic nerve terminals originate from the medial septum and the vertical limb of the diagonal band of Broca and project to the hippocampal formation via the fimbria fornix (Mesulam et al, 1983;Woolf, 1991).…”

Section: Introductionmentioning

confidence: 99%

Reduction in Acetylcholine Release in the Hippocampus of Dopamine D5 Receptor-Deficient Mice

Laplante

Sibley

Quirion

2004

Neuropsychopharmacol

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Activation of the dopamine D 1 -like receptor stimulates acetylcholine (ACh) release in the hippocampus, apparently through the molecularly defined d5 receptor. In the present study, we used a transgenic mouse completely deprived of functional d5 receptor (d5À/À) to confirm the role and elucidate the possible function of the d5 receptor subtype on hippocampal cholinergic neurotransmission. ACh release was measured using in vivo microdialysis in the mouse dorsal hippocampus of 4 months old homozygous (d5À/À), heterozygous (d5 þ /À), and the wild-type (d5 þ / þ ) littermates. Using the no net flux technique, a significant reduction in basal hippocampal ACh level was found in the d5À/À compared to d5 þ /À and d5 þ / þ mice. Moreover, the administration of SKF 38393, a D 1 -like receptor agonist, systemically (2.0 and 10.0 mg/kg ip), or locally through the dialysis probe (10 and 50 mM), produced a dose-dependent enhancement of ACh release in the d5 þ / þ , a moderate stimulation in the d5 þ /À but had no effect in the d5À/À mice. Quantitative receptor autoradiography revealed significant increases in M 1 -like but not in M 2 -like muscarinic receptor binding sites in the hippocampal formation. These results confirm and extend the role of the d5 receptor in the modulation of hippocampal ACh release and provide evidence for long-term alteration of hippocampal cholinergic neurotransmission resulting from the absence of the d5 receptors including chronically reduced ACh release and change in M 1 -like receptor levels.

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Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies

Cited by 615 publications

References 470 publications

Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a streptozotocin model of Alzheimer’s disease

Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a streptozotocin model of Alzheimer’s disease

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

Reduction in Acetylcholine Release in the Hippocampus of Dopamine D5 Receptor-Deficient Mice

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