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Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

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Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
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Cranial manipulation affects cholinergic pathway gene expression in aged rats.

Ramu Anandakrishnan1,2,3, Hope Tobey4, Steven Nguyen5

  • 1Biomedical Sciences, Edward Via College of Osteopathic Medicine, Blacksburg, VA, USA.

Journal of Osteopathic Medicine
|January 7, 2022
PubMed
Summary

Osteopathic cranial manipulative medicine (OCMM) improved spatial memory in aged rats by altering gene expression in neuronal pathways. This suggests OCMM may be a low-risk treatment for age-related dementia.

Keywords:
Alzheimer’s diseasecholinergic pathwaydementianeurotransmissionosteopathic cranial manipulation

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Area of Science:

  • Neuroscience
  • Genomics
  • Integrative Medicine

Background:

  • Age-dependent dementia affects a growing older population.
  • Pharmacological dementia treatments have limitations due to comorbidities and side effects.
  • Nonpharmacological therapies, like osteopathic cranial manipulative medicine (OCMM), are being explored as alternatives.

Purpose of the Study:

  • To investigate the effect of OCMM on gene expression in aged rats.
  • To identify molecular mechanisms potentially explaining OCMM-induced improvements in spatial memory.
  • To build upon previous pilot study findings of improved spatial memory after OCMM treatment.

Main Methods:

  • Elderly rats received daily OCMM for 7 days.
  • Brain tissue was collected for RNA extraction and next-generation sequencing.
  • Transcriptome analysis was performed using Cufflinks software to quantify RNA expression levels.

Main Results:

  • OCMM significantly affected the expression of 36 neuronal genes (FDR < 0.004).
  • Top differentially expressed genes were involved in cholinergic neurotransmission, crucial for cognitive function.
  • 39.9% of 426 significant differentially expressed genes are implicated in neurological disorders.

Conclusions:

  • Findings support further, larger-scale studies on OCMM's molecular mechanisms.
  • OCMM shows potential as a low-risk adjunct treatment for age-related dementia.
  • Clinical validation of OCMM could offer a novel therapeutic option for conditions like Alzheimer's disease.