Studies

Most citations used are taken from the NLM database and are in the public domain.

Choline Deficiency Attenuates Body Weight Gain and Improves Glucose Tolerance in ob/ob Mice

https://www.hindawi.com/journals/jobe/2012/319172/

Cholinergic function and neural control of GH secretion. A critical re-appraisal

http://www.eje-online.org/content/137/4/338.full.pdf
Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice

https://academic.oup.com/endo/article-abstract/159/4/1844/4917524
Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: Link to brain reductions in acetylcholine

https://content.iospress.com/articles/journal-of-alzheimers-disease/jad00475
Involvement of Brain Catecholamines and Acetylcholine in Growth Hormone Deficiency States
– Why don’t our children grow well?

https://link.springer.com/article/10.2165/00003495-199141020-00002

Cholinergic neurotransmission and olfactory function in obstructive sleep apnea syndrome: a TMS study. What are the implications for OSA in Down syndrome?

https://www.ncbi.nlm.nih.gov/pubmed/28899520

Low levels of MicroRNA 132 result in disruption of FOXP2, the human speech gene.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660991/

MicroRNA-132 regulates recognition memory and synaptic plasticity in the perirhinal cortex – this is CREB responsive. CREB is presently activated by PQQ

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488600/#!po=5.35714
MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways

https://www.biorxiv.org/content/biorxiv/early/2018/02/21/258509.full.pdf
microRNA-132: a key noncoding RNA operating in the cellular phase of Alzheimer’s disease – Very important study

https://www.fasebj.org/doi/full/10.1096/fj.201601308

Very Important
MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process – this may explain seizures in DS.

https://www.hindawi.com/journals/np/2016/5108489/

Advances in Roles of miR-132 in the Nervous System – see Luteolin

https://www.frontiersin.org/articles/10.3389/fphar.2017.00770/full

Luteolin Induces microRNA-132 Expression and Modulates Neurite Outgrowth in PC12 Cells

https://www.semanticscholar.org/paper/Luteolin-Induces-microRNA-132-Expression-and-in-Lin-Chiu/2e88f43824d6dfad9c3fb58663db9c7ea6ae1c68
BDNF–ERK–CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice

http://jpn.ca/wp-content/uploads/2014/09/39-5-348.pdf
Other diseases

BioMed Central
Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945024/?report=reader

Research on acetylcholinesterase inhibitor Huperzine A
https://www.sciencedirect.com/science/article/pii/S0009898114001090?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/12117361

/acetylcholinesterase inhibitor
https://www.ncbi.nlm.nih.gov/pubmed/19160328
https://jamanetwork.com/journals/jamaneurology/fullarticle/782409

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(16)30082-5.pdf

https://www.researchgate.net/publication/9049541_Effects_of_Donepezil_on_Cognitive_Functioning_in_Down_Syndrome

Safety
https://examine.com/supplements/huperzine-a/

Drugs and their effects

https://www.frontiersin.org/articles/10.3389/fnbeh.2015.00265/full
Cholinergic System in DS

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.869.4655&rep=rep1&type=pdf

High acetylcholinesterase activity in newborn DS brain
https://www.sciencedirect.com/science/article/pii/0014488685901840
14 year old DS boy in regression
https://www.ncbi.nlm.nih.gov/pubmed/26143664

Trial of inhibitor
https://www.ncbi.nlm.nih.gov/pubmed/12117361

Trial
https://www.ncbi.nlm.nih.gov/pubmed/11921156

AD nursing home patients 2 blind
https://www.ncbi.nlm.nih.gov/pubmed/11843990

ACHe activity in lymphocytes
https://www.sciencedirect.com/science/article/pii/S0009898114001090?via%3Dihub

Elevated homocysteine and elevated acetylcholinesterase
https://www.ncbi.nlm.nih.gov/pubmed/24590316Overview

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648782/

Huperzine A and norepinephrine
https://www.ncbi.nlm.nih.gov/pubmed/17636406

Oral same as above
https://www.ncbi.nlm.nih.gov/pubmed/17636406

Dopamine Hup A vs. Donepizil
https://www.nature.com/articles/aps2006153

Justinformed talk
Huperzine A dosing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269774/

Against iron overload
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099413/

Against APP apoptosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525852/

Mitochondrial and APP protection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003111/

Pharmaceutical and therapeutic potential
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863551/

Role of plant alkaloids
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859479/
Multiple targets
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC508

https://www.spandidos-publications.com/10.3892/ijmm.2013.1546
Progress in study

https://www.nature.com/articles/aps20061

Choline and growth hormone

https://www.ncbi.nlm.nih.gov/pubmed/15482372

https://www.ncbi.nlm.nih.gov/pubmed/15482372
https://www.ncbi.nlm.nih.gov/pubmed/639755

HGH in this study but not TSH

https://www.ncbi.nlm.nih.gov/pubmed/19215369

https://www.ncbi.nlm.nih.gov/pubmed/12200751

Choline and linear growth

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919529/

Egg consumption and linear growth

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024369/

Acetylcholine and hypothyroidism

https://www.ncbi.nlm.nih.gov/pubmed/24520241

And obesity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737921/

Deficiency and obesity

https://jnnp.bmj.com/content/87/12/1368

Choline and the thymus

https://academic.oup.com/endo/article-abstract/30/4/574/2773408?redirectedFrom=fulltext

T- lymphocytes and Ach

https://www.sciencedirect.com/science/article/pii/S0024320501012371

MicroRNA 132 upregulated by Luteolin

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043304#s3

Cognition

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252552/
https://www.ncbi.nlm.nih.gov/pubmed/28642069

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733524/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364589/

Acetylcholinesterase significantly higher in mouse model

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034871/

Acetylcholinesterase inhibitors in young and middle aged mice. This study showed excellent results in younger mice but no significant results in old mice. But, I don’t think we can include young adults with DS in the no significant difference group. It will not induce growth but due to the life long need for this neurotransmitter, I think we use it even in adults beyond 40 years. Mice aren’t people. There are over 700 additional proteins in the mouse model.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246382/#!po=11.5385

Timing the sooner the better

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594009/

Yet here we have accelerated loss with age.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704550/

In vivo MRI shows depleted acetylcholine activity in mouse model circuitry deficits

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771203/
Acetylcholinesterase inhibitor in mouse model

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216618/

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome

On Acetylcholine induced seizures

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771384/

Choline availability and acetylcholine synthesis in the hippocampus of acetylcholinesterase-deficient mice.

https://www.ncbi.nlm.nih.gov/pubmed/18023504

Alzheimer’s disease and Down’s syndrome: roles of APP, trophic factors and ACh.

https://www.ncbi.nlm.nih.gov/pubmed/11814559

3H]vesamicol binding in human brain cholinergic deficiency disorders.

https://www.ncbi.nlm.nih.gov/pubmed/2151294

Alzheimer’s Disease: Targeting the Cholinergic System

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787279/#!po=22.2973

Important read thoroughly

Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466476/

Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095804/

Various chapters on AChE

https://www.sciencedirect.com/topics/neuroscience/acetylcholinesterase

Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells

https://www.nature.com/articles/aps2005101

Cholinergic effects on human gastric motility.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1727654/

GASTROINTESTINAL PHYSIOLOGY

https://www.kumc.edu/AMA-MSS/Study/phys4.htm

The cholinergic system in Down’s syndrome

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.869.4655&rep=rep1&type=pdf
Timing of therapies for Down syndrome: the sooner, the better

https://www.frontiersin.org/articles/10.3389/fnbeh.2015.00265/full

Oleic Acid and Cholinergic dysfunction in Down Syndrome Models of
the Central Nervous System

http://www.jneurology.com/articles/oleic-acid-and-cholinergic-dysfunction-in-down-syndrome-models-of-the-central-nervous-system.pdf

Donepizil (A pharmaceutical acetylcholinesterase inhibitor) doses higher than Huperzine A. We need to find an exact dose comparison

Adults and children benefited from acetylcholinesterase inhibitors
http://www.jneurology.com/articles/oleic-acid-and-cholinergic-dysfunction-in-down-syndrome-models-of-the-central-nervous-system.pdf

Piracetam and acetylcholine receptors

https://en.m.wikipedia.org/wiki/Piracetam

EGCG Enhances effect of Huperzine A

https://www.researchgate.net/publication/26685829_Green_tea_polyphenol_–epigallocatechin-3-gallate_enhances_the_inhibitory_effect_of_huperzine_A_on_acetylcholinesterase_by_increasing_the_affinity_with_serum_albumin. ***

Hup A and autoimmune diseases associated with DS

Cholinergic modulation of inflammatory diseases: role in the amelioration of type 1 diabetes (IRC4P.452)

http://www.jimmunol.org/content/194/1_Supplement/57.5

Acetylcholine and Thyroid

http://fluoroquinolonethyroid.com/wp-content/uploads/2014/11/References-3.pdf

Effects of thyroxine and donepezil, a pharmaceutical acetylcholinesterase inhibitor,on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1
and SNAP-25 expression in hypothyroid adult rats

https://www.spandidos-publications.com/mmr/11/2/775/download

Dysautonomia and Gastrointestinal Dysmotility and Acetylcholine

https://www.mayomedicallaboratories.com/articles/features/autoimmune/

A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924965/

Non cholinergic effects of Huperzine A

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137276/

Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior

https://www.cell.com/neuron/abstract/S0896-6273(12)00802-1

Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice

https://academic.oup.com/endo/article-abstract/159/4/1844/4917524?redirectedFrom=fulltext
RCAN1 Knockdown Reverts Defects in the Number of Calcium-Induced Exocytotic Events in a Cellular Model of Down Syndrome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043644/#!po=3.65854

Antisense miR-132 blockade via the AChE-R splice variant mitigates cortical inflammation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314396/#!po=22.9730

New perspectives for multi-level regulations of neuronal acetylcholinesterase by dioxins.

https://www.ncbi.nlm.nih.gov/pubmed/27374124

miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway.

https://www.ncbi.nlm.nih.gov/pubmed/26052826

Symptoms of high Acetylcholine

http://mindrenewal.us/page13.html

Alzheimer-like neurotransmitter deficits in adult Do

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1032086/

Acetylcholine and aromatic amine systems in postmortem brain of an infant with Down’s syndrome
AChE was extraordinary high

https://www.sciencedirect.com/science/article/pii/0014488685901840

Sleep Disorders Linked To Faulty Brain Chemistry, Study Finds low acetylcholine

https://www.sciencedaily.com/releases/2003/07/030708092417.htm

Obstructive sleep apnea is related to a thalamic cholinergic deficit in MSA.

https://www.ncbi.nlm.nih.gov/pubmed/12847153

Reduction of Sleep-disordered Breathing after Physostigmin an acetylcholinesterase inhibitor

https://www.atsjournals.org/doi/full/10.1164/rccm.200211-1344OC

Donepezil, acetylcholinesterase inhibitor, Improves Obstructive Sleep Apnea in Alzheimer Disease: A Double-blind, Placebo-controlled study

https://www.medscape.com/viewarticle/576092_4

Effects of huperzine A on acute hypobaric hypoxic-induced apoptosis of hippocampal neurons

https://www.researchgate.net/publication/293118784_Effects_of_huperzine_A_on_acute_hypobaric_hypoxic-induced_apoptosis_of_hippocampal_neurons_in_rats

Cholinergic Pathways in the Lungs and Anticholinergic Therapy for Chronic Obstructive Pulmonary Disease

https://www.atsjournals.org/doi/pdf/10.1513/pats.200504-043SR

Cholinergic Regulation of Airway Inflammation and Remodelling

https://www.hindawi.com/journals/ja/2012/681258/

Cholinergic Modulation of Type 2 Immune Responses

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742746/

Autoregulation of Acetylcholine Release and Micro-Pharmacodynamic Mechanisms at Neuromuscular Junction: Selective Acetylcholinesterase Inhibitors for Therapy of Myasthenic Syndromes

Causes acute muscle weakness

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052098/

Cholinergic modulation and Memory Function

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jnc.14052

Acetylcholine Neuromodulation in Normal and Abnormal Learning and Memory: Vigilance Control in Waking, Sleep, Autism, Amnesia and Alzheimer’s Disease

https://www.frontiersin.org/articles/10.3389/fncir.2017.00082/full
Stimming

Acetylcholine drug alleviates autism-like behaviors in mice

https://www.spectrumnews.org/news/acetylcholine-drug-alleviates-autism-like-behaviors-in-mice/

In Autism the kids have fewer acetylcholine receptors, in DS, the kids have less acetylcholine. The result is pretty much the same.

https://www.sciencedaily.com/releases/2004/10/041030131949.htm

Nicotinic Acetylcholine Receptors in Autism Spectrum Disorders: Therapeutic Implications

https://link.springer.com/referenceworkentry/10.1007%2F978-1-4614-4788-7_37