Cell loss in the locus coeruleus in senile dementia of Alzheimer type

Tomlinson, B. E.; Irving, Dorothy; Blessed, G.

doi:10.1016/0022-510x(81)90031-9

Cited by 435 publications

(157 citation statements)

References 7 publications

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“…Indeed, drugs that affect these neuromodulators substantially reduce the benefits of VNS therapy in tinnitus patients [45], indicating that these neuromodulatory pathways are necessary for the effects of VNS. Several diseases affect cell number and function in these neuromodulatory systems, including Alzheimer disease, PD, chronic alcoholism, Down syndrome, TBI, and PTSD [118][119][120][121][122][123][124][125][126]. Comorbidity with these and other diseases that impair neuromodulatory function may limit the effects of VNS.…”

Section: Challenges For Translating Vns Therapies Into Clinical Practmentioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

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Section: Challenges For Translating Vns Therapies Into Clinical Practmentioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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“…Presynaptic and postsynaptic markers are decreased, trophic factors, neurotransmitters, and their respective receptors are likewise reduced, as is the neuronal glucose transporter-3 (Simpson et al, 1994), and disturbances in axonal transport linked with neurofibrillary tangles and microtubule disarrangement are evident (Querfurth and LaFerla, 2010). The basal forebrain cholinergic system degenerates (Whitehouse et al, 1981;Sassin et al, 2000) along with noradrenaline-containing neurons of the locus coeruleus (Tomlinson et al, 1981), and there are decreases in levels of dopaminergic, serotoninergic, and somatostatin markers in various brain areas (Rossor et al, 1980;Arai et al, 1984). The glutamatergic system is also affected, with excessive activation of glutamate receptors resulting in neuronal Ca 2 + overload and possibly, excitotoxic death (Hynd et al, 2004).…”

Section: Neuronal Dysfunctionmentioning

confidence: 99%

Neurovascular function in Alzheimer's disease patients and experimental models

Nicolakakis

Hamel

2011

J Cereb Blood Flow Metab

132

118

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The ability of the brain to locally augment glucose delivery and blood flow during neuronal activation, termed neurometabolic and neurovascular coupling, respectively, is compromised in Alzheimer's disease (AD). Since perfusion deficits may hasten clinical deterioration and have been correlated with negative treatment outcome, strategies to improve the cerebral circulation should form an integral element of AD therapeutic efforts. These efforts have yielded several experimental models, some of which constitute AD models proper, others which specifically recapture the AD cerebrovascular pathology, characterized by anatomical alterations in brain vessel structure, as well as molecular changes within vascular smooth muscle cells and endothelial cells forming the bloodbrain barrier. The following paper will present the elements of AD neurovascular dysfunction and review the in vitro and in vivo model systems that have served to deepen our understanding of it. It will also critically evaluate selected groups of compounds, the FDA-approved cholinesterase inhibitors and thiazolidinediones, for their ability to correct neurovascular dysfunction in AD patients and models. These and several others are emerging as compounds with pleiotropic actions that may positively impact dysfunctional cerebrovascular, glial, and neuronal networks in AD.

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“…The NA circuitry is involved in multiple physiological processes, including arousal, wakefulness, memory and motor functions as well as stress and mood regulation [39,9,18,73,17,11,97]. Several clinical studies indicate degenerative changes of the central noradrenergic system in Alzheimer's disease [12,22,44,65,103] as well as in Parkinson's disease and in Down's syndrome [44]. Impairment of this monoamine system is also involved in major depressive disorder [93,18].…”

Section: Introductionmentioning

confidence: 99%

Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer’s disease

et al. 2015

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Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet the role of a somatostatin signal-

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Cell loss in the locus coeruleus in senile dementia of Alzheimer type

Cited by 435 publications

References 7 publications

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Neurovascular function in Alzheimer's disease patients and experimental models

Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer’s disease

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