Can Melatonin Reverse Prevent Neurogenerative Disease?

The pineal production of melatonin (and gonadotropins) is under photoperiod feedback via nerve circuits with weak or strong synapticity. 

Therefore, the early changes of Alzheimer's pathology is reduced BDNF, reduced neuroplasticity, reduced synapticity.  Melatonin is protective of apoptosis or loss of synapses that have weak activity or signaling frequency.  The result is less output for the retinal sensing cells of photoperiod which are separate from the rods and cones.  Melatonin as an antioxidant becomes weakly produced and therefore weakly protective to the the damage to synapses first, cell function second and neurons third. 

In the Alzheimer's animal model Oxys rodents the damage occurs before beta amyloid deposition or at the soluble beta amyloid state which triggers the inflamasome to damage mitochondria and produce pyroptosis that precedes apoptosis or cell death.  This results in lowered glucose metabolism in early affected areas of brain as seen on glucose based PET scans.  Described as impaired insulin signaling, it might also be a weakened ability to respond to the given insulin effect.  Melatonin the antioxidant reduces inflamasome triggering restoring and reducing damage to synapses, (insulin) cell function second and neuron survival lastly.

Reducing inflammation and improving synapticity, nerve (and somatic cells) function and preventing their escalation to the point of cell death is the heart of my conjecture to prevent neurodegenerative diseases.

To wit.  Health + BDNF (a structural and metabolic turbocharger) - inflamasome.

Healthy diet, exercise, stress reduction plus inflamasome blocking with MELATONIN.

Disordered sleep, depression and stress or learned helplessness are strongly associated with Dementia.  These are symptoms of low BDNF AND low Melatonin.  Here Exogenous Melatonin reversed the early changes of Alzheimer's in this rodent model of the disease.

Conjecture:  Early use of Melatonin will reverse early neurodegeneration changes that lead to dementia.  An early casualty in the disease process is pineal gland circuits loss of synapses, then cell function and then neuron loss.  

In Diabetes the goal is preserve and restore the insulin producing beta cells, their function and their signaling.

In Dementia the goal is preserve and restore the melatonin and gonadotropin producing pineal cells, their function and their signalling.

This may require exogenous insulin (and inappropriate glucagon insulin antagonism) AND Melatonin.  Diabetics have higher prevalence of low testosterone and dementia.  I believe the equality above reveals the preserve and restore potential of BDNF and Melatonin.

Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease 

http://link.springer.com/article/10.1007/s10522-014-9547-7

Can Melatonin Prevent and Ameliorate Bipolar Disease in at Risk and Affected?

The Downstream Targets of Complex I Dysfunction in Bipolar Disorder

This article is supplementary to the adolescent monocyte macrophage inflammatory findings in progeny of a bipolar parent in advance of expressed disease.  Complex 1 is one of 5 complexes in the mitochondrial electron transport chain that produces ATP or cellular energy.

To wit, in this article older bipolar patients are inflamed and specifically show dysfunction in Complex 1, the downstream target of inflammatory damage to mitochondrial energy production.

Ubiquinol the reduced form of CoQ10, specifically is involved in complex 1 and is an antioxidant  in the cytosol that reduces reactive oxygen species that trigger the inflamasome.  Melatonin is a cytosol AND mitochondrial ( a transcellular) antioxidant that might prevent the activation of adolescent immune macrophage cells that are at risk of neuroinflammatory changes.

Conjecture:  Macrophage cells in the brain otherwise named microglial cells become inflamed and activate the systemic and innate immune system of neurons and their energy producing mitochondria.

Conjecture:  Manifest bipolar disease treatment should target Complex 1 with Ubiquinol in addition to Melatonin supplementation to reduce neuroinflammation.

Conjecture:  Adolescents with a bipolar parent should reduce monocyte macrophage and microglial inflammation by nightly Melatonin supplementation.  They should also follow a Mediterranean diet which is inherently higher with dietary sources of Melatonin.

Melatonin is a safe and harmless supplement which may or may not prevent the "downstream targets of complex 1 dysfunction in bipolar disorder."  

https://tspace.library.utoronto.ca/handle/1807/69325

The Downstream Targets of Complex I Dysfunction in Bipolar Disorder

Neurogenesis and BDNF and VEGF

Dad,

The TED talk on the factors that improved neurogenesis (production of new nerve in adult brains) resulting in improved memory and improved mood was informative.  It is perfectly consistent with what I have previously pointed out in my DrLiverman.blogspot.com.  It begs the question and evidentiary exegesis below.

How does intermittent fasting, Exercise, Reservatrol, antidepressants and  brain training increases neurogenesis in the hippocampus (the memory learning center of the brain) thereby improving memory and improving mood?  And the corollary question, how does alcohol, opiates and other depressant drugs, high fat diet, chemotherapy, sedentary lifestyle and non-stimulating non-learning environment decrease neurogenesis in the hippocampus thereby degrading memory and degrading mood?

Herein is an article comparing studies in rodents and humans verifying exercise and virtual or real environmental enrichment via 1. BDNF (and its pathway) and 2. VEGF (blood vessel growth factor) were fundamental to spatial neurons (bookmarks), neurogenesis, learning, positive mood and neuron survival.

I want to draw your attention to the relation between memory and navigation of actual(or virtual space.)  Prodigious memory feats use memory palaces or a well known location tag for ordered memory objects.  This is akin to a database written on new cells and dendrites (physical connections with other nerves like a clasped handshake) on flash memory in the hippocampus.  Consolidation is the process of transferring those flash memories to cerebral (thinking part of the brain) and  subcortical ( primitive reptile brain) neurons under stress and over time.  This is best accomplished with quality sleep both REM (rapid eye movement dreaming sleep ) and NonREM sleep.

The metabolic health and energy efficiency of those brain cells preserve memory and make them available for use in making new memories or understanding the present in relation to the past and perhaps predicting a possible or likely future.  With exercise, diet and thinking able to increase neurogenesis/ via BDNF, a bio marker of a metabolic turbocharger, and in conjunction with adequate blood flow for energy support from VEGF, it is clear that the exercise, diet and cognitive activity improves and preserves the entire body of cells.

Consider disabled ALS astrophysicist Stephen Hawkins, his body survives decade from a short term terminal disease disconnected from direct brain wiring but enriched from brain activity in a theoretic and virtual realm of physics by the production and sharing of brain produced BDNF.  The BDNF produced is released to peripheral blood and can become a metabolic turbocharger of any cell type.  This is repeatedly demonstrated when exogenous BDNF is injected into organisms and cell cultures.

Lifestyles that promote BDNF improve cellular structure and function and thereby improves life, central executive function (frontal lobe where non-impulsive judgement takes place), mood, social function and the real and virtual environments in which one lives.

One can choose BDNF increasing lifestyle or BDNF decreasing lifestyle with opposite results.

Most do not choose but live a blended lifestyle.  These choices are more impactful at the beginning and end of life before 25 and after 40.

http://www.sciencedirect.com/science/article/pii/S235215461500039X

Environmental enrichment and neurogenesis: from mice to humans

The brain is a dynamic structure that constantly undergoes cellular and molecular changes in response to the environment. Ultimately, these experience-dependent changes modify and shape behavior. One example of this neuroplasticity is the robust and continuous generation of new neurons that occurs in the dentate gyrus (DG) of the hippocampus. These new neurons are thought to play a fundamental role in hippocampus-dependent behavior and are modulated by experience and changes in the environment. In this review, we will focus on the cognitive and molecular relationship between environmental enrichment and adult neurogenesis. In addition, we discuss some of the similarities between the human and animal literature in regards to neurogenesis, hippocampus-dependent behavior, and environmental enrichment.

Current Opinion in Behavioral Sciences 2015, 4:56–62

This review comes from a themed issue on Cognitive enhancement

Edited by Barbara J Sahakian and Arthur F Kramer

For a complete overview see the Issue and the Editorial

Available online 2nd March 2015

http://dx.doi.org/10.1016/j.cobeha.2015.02.005

2352-1546/© 2015 Elsevier Ltd. All rights reserved.