Protective effects of 5-HT1A receptor antagonist and 5-HT2A receptor agonist on the biochemical and histological features in a rat model of Alzheimer’s disease

Afshar, Simin; Shahidi, Siamak; Rohani, Ali Haeri; Asl, Sara Soleimani; Komaki‬, Alireza

doi:10.1016/j.jchemneu.2019.01.008

Cited by 24 publications

(8 citation statements)

References 68 publications

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“…5-HT 1A R is a well-studied member of this subfamily and shows overexpression under Aβ stimulation ( Verdurand et al, 2011 , 2016 ). Treatment with 5-HT 1A R antagonists (e.g., NAD-299 and WAY-100635) has been shown to reduce amyloid plaque deposition, increase levels of hippocampal BDNF, alleviate neuroinflammation and oxidative stress, and improve cognitive deficits in individual animal models of AD ( Afshar et al, 2018 , 2019 ; Wang et al, 2020 ; Table 3 ). These results imply that 5-HT 1A R, in response to specific ligands, is involved in the regulation of AD pathology through multiple pathways.…”

Section: Serotonergic Systemmentioning

confidence: 99%

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

Zong

Zhang

et al. 2022

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, characterized by the accumulation of proteinaceous aggregates and neurofibrillary lesions composed of β-amyloid (Aβ) peptide and hyperphosphorylated microtubule-associated protein tau, respectively. It has long been known that dysregulation of cholinergic and monoaminergic (i.e., dopaminergic, serotoninergic, and noradrenergic) systems is involved in the pathogenesis of AD. Abnormalities in neuronal activity, neurotransmitter signaling input, and receptor function exaggerate Aβ deposition and tau hyperphosphorylation. Maintenance of normal neurotransmission is essential to halt AD progression. Most neurotransmitters and neurotransmitter-related drugs modulate the pathology of AD and improve cognitive function through G protein-coupled receptors (GPCRs). Exercise therapies provide an important alternative or adjunctive intervention for AD. Cumulative evidence indicates that exercise can prevent multiple pathological features found in AD and improve cognitive function through delaying the degeneration of cholinergic and monoaminergic neurons; increasing levels of acetylcholine, norepinephrine, serotonin, and dopamine; and modulating the activity of certain neurotransmitter-related GPCRs. Emerging insights into the mechanistic links among exercise, the neurotransmitter system, and AD highlight the potential of this intervention as a therapeutic approach for AD.

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Section: Serotonergic Systemmentioning

confidence: 99%

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

Zong

Zhang

et al. 2022

Front. Aging Neurosci.

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“…Rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, improves depression-like behaviors in mice, but 5-HT 1A antagonists block these improvements [ 30 ]. On the other hand, the administration of 5-HT 1A antagonists and 5-HT 2A receptor agonists reduced the loss of hippocampal neuronal cells and improved cognitive functions in AD model rats [ 31 , 32 ]. Therefore, 5-HT 1A receptors could play impor-tant roles in the pathogenesis of BPSD in patients with severe dementia regardless of cognitive function.…”

Section: Discussionmentioning

confidence: 99%

5-HT_1A Partial Agonist Tandospirone for Behavioral and Psychological Symptoms in Oldest-old Patients with Dementia at a Special Elderly Nursing Home

Ochi

Mori

Iga

et al. 2021

Clin Psychopharmacol Neurosci

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Objective: To investigate the efficacy of tandospirone, an azapirone anxiolytic similar to buspirone that is used in Japan, for behavioral and psychological symptoms of dementia (BPSD), especially in oldest-old patients. Methods: This was an open-label observational study involving residents with BPSD in a special elderly nursing home between August 2013 and August 2018. The severity of dementia was assessed using the Clinical Dementia Rating (CDR) scale; as the main outcomes, the severity of BPSD was assessed using the Clinical Global Impressions-Severity scale (CGI-S) and Neuropsychiatric Inventory-12 (NPI-12) at baseline and 4 weeks after the maintenance dose of tandospirone was reached. The administration of tandospirone started at 30 mg, divided into three doses per day. Two weeks later, if the efficacy was sufficient based on the clinical nursing record, that dose was continued; if the efficacy was insufficient, the daily dose was increased from 40 mg/day to a maximum dose of 60 mg/day. Results: Thirty-three participants (25 females [76%], mean age 87.1 ± 5.4 years) completed the study. Twenty-three participants (70%) were oldest-old (18 females [78%], mean age 89.9 ± 3.4 years). The mean CDR score was 2.9 ± 0.3 in all participants. Tandospirone treatment showed few or no obvious adverse effects and significantly improved CGI-S scores, as well as total scores and many subscale scores on the NPI-12, in both the sample at large and the oldest-old participants. Conclusion: This study demonstrated the efficacy and safety of tandospirone for BPSD in oldest-old participants.

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“…More and more importance is attached to the relationship between anxiety plots and other alterations, including changed γ-aminobutyric acid levels [ 127 ], increased insulin secretion and insulin resistance [ 128 ], and oxidative stress [ 129 - 131 ], which provides a promising target for anxiolytics. An extensive study on the serotonergic system has revealed a possible target for treating anxiety disorders considering its relationship with memory and oxidative stress, including behavioral/psychological symptoms of AD and dementia [ 132 - 134 ]. Furthermore, one of several mechanisms by which serotonin may directly affect the pathogenesis of AD is to up-regulate the α-secretase activity through 5-hydroxytryptamine (HT)4 receptors [ 135 ].…”

Section: Oxidative Stresses Triggered By Mitochondria Dysfunction Is ...mentioning

confidence: 99%

Brain Mitochondrial Dysfunction: A Possible Mechanism Links Early Life Anxiety to Alzheimer’s Disease in Later Life

Wang¹,

Lu²,

Zhu³

et al. 2022

Aging and disease

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Alzheimer’s disease (AD) is usually manifested in patients with dementia, accompanied by anxiety and other mental symptoms. Emerging evidence from humans indicates that people who suffer from anxiety in their early life are more likely to develop AD in later life. Mitochondria, the prominent organelles of energy production in the brain, have crucial physiological significance for the brain, requiring considerable energy to maintain its normal physiological activities. Net reactive oxygen species (ROS) was produced by mitochondrial impairment, in which oxidative stress is also included, and the production of ROS is mostly more than that of removal. In this paper, we propose that as a critical process in brain pathology, mitochondrial dysfunction caused by anxiety triggering oxidative stress might be a possible mechanism that links early life anxiety to AD in later life. Several pivotal physiological roles of mitochondria are reviewed, including functions regulating glucose homeostasis, which may disrupt in oxidative stress. Increased levels of oxidative stress are constantly shown in anxiety disorder patients, and antioxidant drugs have promise in treating anxiety. In the early stages of AD, mitochondrial dysfunction is concentrated around senile plaques, a landmark lesion composed of aggregated Aβ and Tau protein. In turn, the accumulated Aβ and Tau disrupts mitochondrial activity, and the tricky physiological processes of mitochondria might be significant to the course of AD. In the end, we conclude that mitochondria might present as one of the novel therapeutic targets to block oxidative stress in patients with anxiety disorders to prevent AD in the early stage.

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Protective effects of 5-HT1A receptor antagonist and 5-HT2A receptor agonist on the biochemical and histological features in a rat model of Alzheimer’s disease

Cited by 24 publications

References 68 publications

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

5-HT_1A Partial Agonist Tandospirone for Behavioral and Psychological Symptoms in Oldest-old Patients with Dementia at a Special Elderly Nursing Home

Brain Mitochondrial Dysfunction: A Possible Mechanism Links Early Life Anxiety to Alzheimer’s Disease in Later Life

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Protective effects of 5-HT1A receptor antagonist and 5-HT2A receptor agonist on the biochemical and histological features in a rat model of Alzheimer’s disease

Cited by 24 publications

References 68 publications

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems

5-HT1A Partial Agonist Tandospirone for Behavioral and Psychological Symptoms in Oldest-old Patients with Dementia at a Special Elderly Nursing Home

Brain Mitochondrial Dysfunction: A Possible Mechanism Links Early Life Anxiety to Alzheimer’s Disease in Later Life

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5-HT_1A Partial Agonist Tandospirone for Behavioral and Psychological Symptoms in Oldest-old Patients with Dementia at a Special Elderly Nursing Home