Hyperkinesia, plasma corticotropin releasing hormone and ACTH in senile dementia

Suemaru, Shuso; Hashimoto, Kozo; Suemaru, Kohso; Maeba, Y.; Matsushita, Noriko; Ota, Zensuke

doi:10.1097/00001756-199106000-00009

Cited by 8 publications

(4 citation statements)

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“…Our tauopathy model mice showed phosphorylated tau in the prefrontal cortex and amygdala [15] , which are involved in hyperactive behavior [45] . Hyperactive behavior was also observed among human AD patients [46] . Thus, our tauopathy model mice appeared to reproduce the hyperactive phenotype of tauopathy with dementia.…”

Section: Discussionmentioning

confidence: 84%

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

et al. 2011

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Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions.

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Section: Discussionmentioning

confidence: 84%

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

et al. 2011

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“…Glutamine supplementation showed no significant effect on the hyperactivity of these PS19 mice (p > 0.05) (Figure S7). Phospho-tau accumulation in the prefrontal cortex and amygdala was proposed to induce hyperactive behavior [6,75,76]. Thus, our results suggest the persistence of brain regions driving hyperlocomotion behavior, which is resistant to bioenergetic enhancement.…”

Section: Resultsmentioning

confidence: 62%

Mitochondrial bioenergetics stimulates autophagy for pathological tau clearance in tauopathy neurons

Jia,

Ganesan,

Guan

et al. 2024

Preprint

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Hyperphosphorylation and aggregation of microtubule-associated tau is a pathogenic hallmark of tauopathies and a defining feature of Alzheimer's disease (AD). Pathological tau is targeted by autophagy for clearance, but autophagy dysfunction is indicated in tauopathy. While mitochondrial bioenergetic failure has been shown to precede the development of tau pathology, it is unclear whether energy metabolism deficiency is involved in tauopathy-related autophagy defects. Here, we reveal that stimulation of anaplerotic metabolism restores defective oxidative phosphorylation (OXPHOS) in tauopathy which, strikingly, leads to enhanced autophagy and pronounced tau clearance. OXPHOS-induced autophagy is attributed to increased ATP-dependent phosphatidylethanolamine biosynthesis in mitochondria. Excitingly, early bioenergetic stimulation boosts autophagy activity and reduces tau pathology, thereby counteracting memory impairment in tauopathy mice. Taken together, our study sheds light on a pivotal role of bioenergetic dysfunction in tauopathy-linked autophagy defects and suggests a new therapeutic strategy to prevent toxic tau buildup in AD and other tauopathies.

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“…However, the similarities between signs and CRF‐mediated instantaneous conscious fluctuations in delirium and paradoxical lucidity could provide a unique window to understand neural events and develop an animal model of lucidity. Delirium is an acute disorder of attention and cognition in older people and characterized by the short feedback suppression of CRF in the brain by increased circulating adrenocorticotropic hormone 104 . Studies have indicated that increased corticosteroid level is a risk factor for hyperactive delirium 105 .…”

Section: The Future Of Terminal Lucidity Researchmentioning

confidence: 99%

“…Delirium is an acute disorder of attention and cognition in older people and characterized by the short feedback suppression of CRF in the brain by increased circulating adrenocorticotropic hormone. 104 Studies have indicated that increased corticosteroid level is a risk factor for hyperactive delirium. 105 This evidence proposes an LC-BF/hippocampus circuit as a therapy target for delirium.…”

Section: The Future Of Terminal Lucidity Researchmentioning

confidence: 99%

Unexpected awakenings in severe dementia from case reports to laboratory

Bostancıklıoğlu¹

2020

Alzheimer's & Dementia

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Objective: Case report notions of unexpected memory retrieval in patients with severe dementia near to death are starting to alter the central "irreversible" paradigm of dementia and locate dementia as a problem of memory retrieval, not consolidation. We suggest that the most likely central tenet of this paradoxical memory retrieval is the fluctuation of neuromodulators projecting from the brain stem to the medial prefrontal cortex and the hippocampus. The neuromodulation-centric explanation of this phenomenon aims to open the "irreversible" paradigm of dementia up for discussion and suggest a plausible treatment strategy by questioning how the devastating process of death fluctuates memory performance in severe dementia. Background: Supporting demented patients, who are mostly unresponsive, without making demands or asking a question and regarding them as valuable human beings unexpectedly improve their memory performance around the time of death. New lucidity hypothesis: Around the time of death, neurological signs (hyper-arousal and-attention) of demented people point out that neurotransmitter discharges are dramatically changed. Relatively resistant neuromodulator circuits to neurodegeneration can maintain optimal levels of arousal and attention for memory processing. In this way, unexpected episodes of lucidity can be triggered. Also, corticotropin-releasing peptides might increase mental clarity by increasing the excitability of the neuromodulator circuits. The science of memory retrieval is more complicated and nuanced than retrieval observations in case reports, but the rapid development of new techniques holds promise for future understanding of lucidity in severe dementia. Major challenge for the model: There is no an animal or human model to test this hypothesis; however, the similarities between neurological signs (instantaneous cognitive fluctuations) of delirium and paradoxical lucidity could provide a unique window to understand neural events of terminal lucidity on a modified animal model of delirium. Likewise, similarities between unexpected consciousness signs of terminal lucidity and lucid dreaming suggest that lucid dreaming episodes might be considered a human model for terminal lucidity research.

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Hyperkinesia, plasma corticotropin releasing hormone and ACTH in senile dementia

Cited by 8 publications

References 0 publications

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

Mitochondrial bioenergetics stimulates autophagy for pathological tau clearance in tauopathy neurons

Unexpected awakenings in severe dementia from case reports to laboratory

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