Reserpine Improves Working Memory

Vasantharaja, Raghuraman; Kumar, Abdhesh; Kumar, Ashok; Subramaniam, Jamuna R.

doi:10.4236/jbbs.2016.63012

Cited by 4 publications

(5 citation statements)

References 19 publications

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“…Overall, modulation of ACh-NT as seen with reserpine 19,54,55 , an antihypertensive drug, Glu-NT, and Ca 2+ ions can delay Aβ-induced paralysis, and suppression of Glu-NT can greatly increase ACh-NT in C. elegans. 56 Interestingly, the FOXO transcription factor, daf-16, which is suppressed in the insulin/ insulin-like growth factor signaling, is required for ACh-NT.…”

Section: Discussionmentioning

confidence: 98%

DMSO Delays Alzheimer Disease Causing Aβ-induced Paralysis in C. elegans Through Modulation of Glutamate/Acetylcholine Neurotransmission

Sadananda

Velmurugan

Subramaniam

2021

Annals of Neurosciences

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Background: Alzheimer’s disease (AD), a prevalent neurodegenerative disease with progressive dementia and neurotransmission (NT)-dysfunction-related complications in older adults, is known to be caused by abnormal Amyloid-β (Aβ) peptide and associated amyloid plaques in the brain. Drugs to cure AD are not in sight. Two major excitatory neurotransmitters, glutamate (Glu) and acetylcholine (ACh), and their signaling systems are implicated in AD. Objective: To determine the effect of various NT-altering compounds including fenobam, quisqualic acid, and dimethyl sulfoxide (DMSO) in the protection against Aβ toxicity. Further, to identify the potential mechanism through which the protection happens. Methods: The well-known C. elegans AD model, CL4176, in which human Aβ expression is turned on upon a temperature shift to 25 °C that leads to paralysis, was screened for protection/delay in paralysis because of Αβ toxicity. While screening the compounds, dimethyl sulfoxide (DMSO), a universal solvent used to solubilize compounds, was identified to provide protection. Aldicarb and levamisole assays were performed to identify the contribution of ACh neurotransmission in Αβ toxicity protection by DMSO. Results: One percent and two percent DMSO delayed paralysis by 48% and 90%, respectively. DMSO was dominant over one of the Glu-NT pathway-related compounds, Fenobam-Group I mGluR antagonist. But DMSO provided only 30% to 50% protection against Quisqualic acid, the Glu-agonist. DMSO (2%) delayed ACh-NT, both presynaptic acetylcholine esterase inhibitor (AchEi)-aldicarb and postsynaptic-iAChR-agonst-levamisole induced paralysis, by ∼70% in CL4176. DMSO seems to be altering Ca2+ ion permeability essential for NT as EthyleneDiamine Tetra-Acetic acid (EDTA) and DMSO provided similar aldicarb resistance either combined or alone in wildtype worms. But postsynaptic Ca2+ depletion by EDTA could reverse DMSO-induced levamisole hypersensitivity. Surprisingly, the absence of FOrkhead boXO (FOXO) transcription factor homolog, daf-16 (loss-of-function mutant), a critical transcription factor in the reduced IIS-mediated longevity in C. elegans, abolished DMSO-mediated AldR. Conclusion: DMSO and Fenobam protect against Aβ toxicity through modulation of NT.

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Section: Discussionmentioning

confidence: 98%

DMSO Delays Alzheimer Disease Causing Aβ-induced Paralysis in C. elegans Through Modulation of Glutamate/Acetylcholine Neurotransmission

Sadananda

Velmurugan

Subramaniam

2021

Annals of Neurosciences

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“…1 and Fig 2). The novelty of this study is the drug reserpine identified through the C aenorhabditis elegans lifespan extending 19 and Alzheimer disease(AD) causing amyloid beta toxicity 22 protecting effect, could provide cognitive enhancement in normal and 5XFAD transgenic AD model mice 23 and reduce Aβ aggregates in another AD model mice Tg2576 24 can preserve cognition in hypertensive patients (Fig.1). Given that reserpine is of ancient Ayurvedic medicine origin, the wisdom of the ancestors is praiseworthy.…”

Section: Discussionmentioning

confidence: 99%

“…Independently, in a C. elegans screen, reserpine was found to extend lifespan 19 , albeit, through modulation of acetylcholine release 20 , partially through the action of Goi coupled dopamine receptor, dop-3 21 . More importantly, reserpine could protect against the Alzheimer disease causing Amyloid beta toxicity induced paralysis in C. elegans 22 and improved working memory in the 5XFAD Alzheimer disease model mice 23,24 suggesting reserpine as a potential drug to provide cognitive protection.…”

Section: Introductionmentioning

confidence: 99%

Preservation of cognition in hypertension-treated South Indian rural population

Subramaniam

Rajkumar

Merciline

et al. 2020

Preprint

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Change in diet life style and increased life expectancy has led to the dramatic escalation in old age related complication like cognitive decline leading to dementia. Cardiovascular diseases (CVD) are huge risk factors for dementia, including Alzheimer disease (AD). Hypertension is very well known to cause cognitive impairment. Control of CVD could provide protection against dementia. Earlier in the mouse model of AD, reserpine, an antihypertensive and antipsychotic drug could elicit improvement in the working memory in AD model mice and enhance the same in normal mice. Hence, Cognitive protection in the patients on chronic antihypertensive drug which contains reserpine was evaluated. Cognition in a cohort (in the South Indian rural population) of hypertensive patients (majority age group 50 to 70 years) who have been chronically treated with a combinatorial drug(adelphane/adelphane esidrexsodl by Novaritis Switzerland) consisting of reserpine and hydrazine for years was compared with controls without hypertension. The cohorts were age sex socio-economic education background matched. Cognition was scored using the Tamil version of: Addenbrooke Cognitive Examination-III (ACEIII (Tamil)) and Montreal Cognitive Assessment (Tamil) scales. The composite ACEIII (Tamil) score of control and treated groups were 53.6 and 53.2 respectively. MoCA(tamil) scores (Control :15.1 and Treated: 14.7) did not show much alteration. Further the mean scores of the control and treated groups individual components of cognition in ACE, namely Attention Memory Fluency Language and visuospatial cognitive skills also did not reveal significant difference. Thus controlling blood pressure or hypertension with chronic antihypertensive medication like adelphane/adelphane esirdex (reserpine containing drugs) has retained normal cognition in both genders.

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“…In addition, reserpine was able to provide protection against dementia -Alzheimer disease (a geriatric disease affecting many old people, known to be a huge social and financial burden on society) causing, Aβ-induced toxicity manifested as progressive paralysis, in the C. elegans model [31][32][33]. Similarly, in the AD mouse model, Tg2576, expressing human mutant APP, which causes Aβ aggregates formation and cognitive deficits at ~11 months of age, reserpine reduces the Aβ levels [34] and enhances working memory [35] in the 5XFAD AD model [36]. Further, reserpine is protective against another fatal neurodegenerative disease, amyotrophic lateral sclerosis, again in the C. elegans model [37].…”

Section: Discussionmentioning

confidence: 99%

A Combinatorial Antihypertensive Drug (Reserpine and Hydrazine) Does Not Cause Severe Depression

Subramaniam¹

2018

GGS

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Background and objectives: Reserpine, a traditional Indian Ayurvedic medicine, is approved by the FDA to treat hypertension and for treatment resistant psychosis. The major reported side effect of reserpine is depression. Hence, hypertensive patients on prolonged reserpine treatment were evaluated for occurrence of depression.Methods: One-time cross-sectional evaluation was done in 104 subjects on reserpine and 105 controls, who were matched for age (majority being between 50-70 years old), sex, education, and social background. The Control group had no chronic disease and the treatment group comprised of hypertensive patients who had received reserpine as Adelphane (0.1mg reserpine and 10mg of hydralazine) or Adelphane Esidrex [Novaritis (Basel, Switzerland)] for more than 1 year. Both the groups were asked to answer (and were rated by) Hamilton Depression Rating Scale (HDRS-17-items version). The results were scored, statistically analyzed and plotted with Sigma Plot.Results: Results obtained by the HDRS were classified into normal, and different levels of depression by score-based categorization. Of the 105 control and 104 treated patients, 38% (both control and treated) were normal, 38% control and 48% treated had mild depression while 23.8% control and 13.4% treated had moderate depression. No severe or very severe depression in control or treated group was found.Interpretation and Conclusion: Reserpine does not cause depression even when taken for years. The study is small with ~100 subjects per group. As a proven antihypertensive drug, our results should pave the way to bring reserpine into the mainstream..

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Reserpine Improves Working Memory

Cited by 4 publications

References 19 publications

DMSO Delays Alzheimer Disease Causing Aβ-induced Paralysis in C. elegans Through Modulation of Glutamate/Acetylcholine Neurotransmission

DMSO Delays Alzheimer Disease Causing Aβ-induced Paralysis in C. elegans Through Modulation of Glutamate/Acetylcholine Neurotransmission

Preservation of cognition in hypertension-treated South Indian rural population

A Combinatorial Antihypertensive Drug (Reserpine and Hydrazine) Does Not Cause Severe Depression

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