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
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