The cholinergic system in aging and neuronal degeneration

  title={The cholinergic system in aging and neuronal degeneration},
  author={Reinhard Schliebs and Thomas Arendt},
  journal={Behavioural Brain Research},

Molecular and morphological analyses of basal forebrain cholinergic neurons in mouse models of aging and Alzheimer's disease

During normal aging and Alzheimer’s disease (AD) BFCNs become more vulnerable to dysfunction due to trophic factor withdrawal, cell signaling impairments and other cytopathologic changes.

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

It is concluded that targeting cholinergic glial interactions between neurons and glial cells via α7nACh receptors could regulate neuroinflammation and oxidative stress, relevant to the treatment of several neurodegenerative diseases.

The cholinergic system in the pathophysiology and treatment of Alzheimer's disease.

The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as the authors look ahead to future combination therapies that address symptoms as well as disease progression.

The brain cholinergic system in neurodegenerative diseases

  • G. Pepeu
  • Biology
    Neurobiology of Aging
  • 2016

Neuropathological approaches to cerebral aging and neuroplasticity

To obtain further insights into the mechanisms of brain plasticity and adult neurogenesis, as the basis for prevention and potential therapeutic options, is a major challenge of modern neurosciences.

Accelerated aging of the GABAergic septohippocampal pathway and decreased hippocampal rhythms in a mouse model of Alzheimer's disease

It is shown that innervation of the GABAergic SHP decreases during normal aging, and it is demonstrated that hippocampal θ and γ rhythm power spectra are markedly diminished in 8‐mo‐old behaving mice expressing mutated hAPP.

Regulators of cholinergic signaling in disorders of the central nervous system

The available data suggest that these small non-coding RNA regulators may include promising biomarkers for predicting disease course and assessing treatment responses and might also serve as drug targets to attenuate signaling cascades during overwhelming inflammation and to ameliorate regenerative capacities of neuroinflammation.

Age-related loss of calcium buffering and selective neuronal vulnerability in Alzheimer’s disease

It is concluded that the loss of calcium buffering capacity in these neurons and the resultant pathological increase in intracellular calcium are permissive to tangle formation and degeneration.

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment

Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of Cholinergic treatment at this disease stage.



The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease

Understanding the molecular mechanisms underlying the interrelationship between cortical cholinergic dysfunction, β-amyloid formation and deposition, and tau pathology in Alzheimer’s disease, would allow to derive potential treatment strategies to pharmacologically intervene in the disease-causing signaling cascade.

Cholinergic Neuronal and Axonal Abnormalities Are Present Early in Aging and in Alzheimer Disease

The results indicate that basal forebrain cholinergic neuron abnormalities are present very early in aging and in the course of AD, and despite the morphologic alterations, choline acetyltransferase activity, but not necessarily normal neuron functions, may be preserved.

Basal Forebrain Cholinergic Dysfunction in Alzheimer’s Disease – Interrelationship with β-amyloid, Inflammation and Neurotrophin Signaling

  • R. Schliebs
  • Biology, Psychology
    Neurochemical Research
  • 2005
Understanding the molecular mechanisms underlying the interrelationship between cortical cholinergic dysfunction, β-amyloid formation and deposition, as well as local inflammatory upregulation, would allow to derive potential treatment strategies to pharmacologically intervene in the disease-causing signaling cascade.

Impairment in memory function and neurodegenerative changes in the cholinergic basal forebrain system induced by chronic intake of ethanol.

  • T. Arendt
  • Biology, Psychology
    Journal of neural transmission. Supplementum
  • 1994
The hypothesis is formulated in the present paper that mental dysfunction observed after chronic ethanol consumption can largely be attributed to a degeneration of the cholinergic pathway of the ascending activation system resulting in an impairment of cortical activation, clinically appearing as the "syndrome of partial Cholinergic deafferentations of the cortical mantle".

Cholinotrophic molecular substrates of mild cognitive impairment in the elderly.

The concept that from a neurotrophic pathobiologic perspective, MCI is already early AD is supported, as there is a shift in cholinotrophic molecular events in MCI and early AD which may lead to cell dysfunction and eventual cell death over the course of the disease.

The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease.

Dysfunction of nerve growth factor (NGF) and its high (TrkA) and low (p75NTR) affinity receptors has been suggested to underlie the selective degeneration of the nucleus basalis (NB) cholinergic

Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications

Drugs treating the multiple pathologies and clinical symptoms in AD (e.g., M1 cholinoceptor and/or galaninergic drugs) should be considered for a more comprehensive treatment approach for cholinergic dysfunction.

Functional Recovery of Cholinergic Basal Forebrain Neurons under Disease Conditions: Old Problems, New Solutions?

A review of the involvement of cholinergic dysfunction in the pathogenesis of severe neurological conditions, including stroke, traumatic brain injury, virus encephalitis and Alzheimer's disease, and the critical role of pro-inflammatory cytokines as common mediators of cholinergic neuronal damage is emphasized.