Steroid Hormones & Memory: Pregnenolone

Steroid Hormones That Effect Memory

• Pregnenolone, Estrogen, Progesterone, Testosterone, DHEA, and cortisol all effect memory.

Pregnenolone Production and Function

• Pregnenolone functions as a precursor to DHEA, estrogen, progesterone, testosterone, and cortisol.
• Cholesterol is needed for pregnenolone production.
• Pregnenolone is not as effectively made if total cholesterol dips below 140.
• The production of pregnenolone declines as people age.
• By age 75, there is typically a 65% decline compared to age 35.
• Pregnenolone's activities include regulating the balance between excitation and inhibition in the nervous system
• It also increases resistance to stress
• It improves physical and mental energy
• It enhances nerve transmission and memory
• It modulates NMDA receptors.
• Pregnenolone directly influences acetylcholine release
• It reduces pain and inflammation.
• It blocks the production of acid-forming compounds
• It promotes new nerve growth factor
• It modulates GABA.
• Pregnenolone helps to repair nerve damage and improves sleep.

Other Information Regarding Pregnenolone

• Pregnenolone and its metabolic derivatives have beneficial effects in the brain, enhancing memory and learning, and reversing cognitive functions.
• A decreased level of pregnenolone is observed in neuroinflammatory diseases such as Alzheimer's, which emphasizes its role in neuroprotection and neuroregeneration.
• Pregnenolone can promote the degeneration of key immune signaling proteins to suppress inflammation.
• It is suggested that pregnenolone may protect the brain from cannabis intoxication.
• Use particular caution with pregnenolone with patients who have seizures, because it could lower the seizure threshold.
• Elevated pregnenolone levels may cause acne
• It can also cause drowsiness, muscle aches, fluid retention, headache, heart racing, and/ or insomnia due to overstimulation.
• Elevated levels may also cause irritability, anger, and anxiety.

Causes and Symptoms of Low Pregnenolone

• The aging process, hypothyroidism, pituitary tumors, eating too many saturated fats and trans fats, and low cholesterol levels can all cause low pregnenolone.
• A severe illness can also be a cause, because pregnenolone will prioritize producing cortisol versus other hormones.
• Symptoms of deficiency include arthritis, depression, and fatigue; inability to deal with stress, insomnia, lack of focus, and memory decline.

Estrogen and Progesterone

• Sex hormones and their metabolites have actions on the brain.
• Sex hormones have direct and indirect effects on neurons, glia, and vessels.
• Effects require steroid receptor-mediated gene expression, transcription, and translation, which require days to manifest changes
• Sex hormones act directly on ion channels, activating changes in seconds to minutes when coupled to second messengers and early-intermediate genes.
• These include CFOs and Jun.
• Delayed action of estrogen and progesterone is a genomic response mediated by steroid receptors.
• It impacts nerve growth and differentiation and modulation of intramembranous protein particles.
• Delayed action can result in Cytoarchitectural changes and synaptologic changes in the hypothalamus.
• Estrogen increases choline acetyl transferase synthesis and stimulates neuronal NO synthase; it also increases degradation of monoamine oxidase.
• Estrogen also increases the number of NMDA sensitive receptors in the hippocampus.
• Estrogen increases G-protein coupled cAMP dependent kainate-induced ion current in CA1 neurons,

Rapid Action of Estrogen and Progesterone

• Estrogen modulates dopamine receptor binding in striatum and increases K+ permeability of postsynaptic membrane in amigdala neurons.
• Estrogen causes Postsynaptic potentiation of non-MNDA receptors in CA1 neurons - It can also impact the calcium transport mechanism in nerve endings.
• Progesterone stimulates release of dopamine in striatal tissue, and stimulates release of GnRH from hypothalamic neurons.
• Progesterone modulates oxytocin receptor binding in the hypothalamus and inhibits opioid receptor binding.
• Progesterone effects the potentiation of GABA.
• Progesterone directs the incorporation of steroids into the cell membrane.

Sex Hormones and Memory Overview

• Pregnenolone, pregnenolone sulfate, progesterone, allopregnanolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and estradiol all have modulatory effects on the release of neurotransmitters.
• Neurotransmitters affected by memory include glutamate, GABA, acetylcholine, NE, dopamine, and 5-HTP.
• Neurotransmitter effects take place in areas of the brain involved in cognition, emotion, motor, memory and learning.
• Mechanisms of affect of neurotransmitters are complicated.
• Numerous involve rapid non-genomic effects on presynaptic receptors and ion channels.
• Presynaptic receptors and ion channels that are affected:
  • Sigma-1 receptor
  • Alpha(1) receptor
  • Nicotine receptor
  • D1 receptor
  • NMDA receptor
  • GABA(A) receptor
  • L-type Ca(2+) channels
• Sex hormones are important regulators of synaptic transmission in the CNS, including brain function.

Estrogen and Memory

• Estrogen's effects within the CNS and hippocampus are governed by estrogen receptors alpha and beta.
• Estrogen Increases blood flow and Increases glucose and oxygen to the neurons
• Estrogen Increases neurotransmitters and keeps the blood-brain barrier working
• Estrogen increases sensitivity to nerve growth factor and protects neurons.
• Estrogen decreases neuronal generation of Alzheimer's beta-amyloid peptides
• Functions as a natural antioxidant, increases manual speed and dexterity, and increases the availability of acetylcholine
• It boosts by 30% NMDA receptors to maintain the strength and durability of synaptic connections involved in creating long-term memories
• Further it Decreases distractibility and Turns on progesterone receptors
• Women who have had unilateral or bilateral oophorectomies before menopause have an increased risk of memory loss.
• Younger women that do not cycle regularly due to intensive sports participation, estrogen has helped with memory.
• More research needs to be done in this area.
• Those in menopause may experience noticable Cognitive Symptoms
• Women may have symptoms of cognitive changes as early as fifteen years before menopause.

Warga's Hormonal Misconnect Syndrome

• A list of symptoms includes Losing your train of thought often, Forgetting what you came into a room to get, Not being able to concentrate as well upon demand, Feeling foggy, hazy, and cotton-headed and not being able to clear it up at will, Experiencing a though blockade: an inability to pull ideas out at will, and Fluctuating agility in prioritizing
• Speech changes may include naming difficulties for long-known names, finding yourself at a loss for words, experiencing "It's on the tip of my tongue but I can't get it out" sensation or Making malapropisms.
• Changes may also include Reversing whole words while speaking.
• One may also find themselves Reversing the first letters of words while speaking.
• One may start Experiencing "echo" words as unintentional intrusions or Relying on "filler" words more often" "whatchamacallit," "that thing," "you know what I mean"
• Altering Organization of sentences and ideas less efficiently while speaking.
• There will be changes in the "Beam" of attention
• This includes Blinking social attention when interested and interacting (listening but not attending).
• This also includes experiencing Blanking-out amnesia or increased distractibility.
• This impacts Thinking, Speech, Memory and The Beam of Attention.
• Cognitive/behavioral/speech episodes are mis-hits due to hormonal misconnections.
• The mind's intentions are not producing the right physiological connections in the preexisting circuitry and/or chemical flow patterns of the brain, a the effects of declining ovarian function and estrogen
• These symptoms are not a normal part of aging
• Symptoms occur on a brain heavily dependent on estrogen, affecting functions related to neurotransmitter function.
• Affects system related to Serotonin, Acetylcholine, Noradrenaline, transmission of dopamine.

How Estrogen Alters Brain Neurochemistry

• Alters the supplies of multiple neurotransmitters: serotonin, dopamine, acetylcholine, glutamate, GABA, noradrenaline
• Affects critical enzymes (choline acetyltransferase) and Impacts the brain’s uptake of glucose.
• It stimultes nerve growth factors and affects neuropeptides
• The above functions are related to memory, learning, and mood:
• Estrogen Increases Choline Acetyltransferase Activity in Specific Basal Forebrain Nuclei.
• Estrogen Stimulates Neuronal Nitric Oxide (NO) Synthase
• This in turn stimulates the Changes in the Catabolism of Serotonin in the Brain.
• Estrogen increases the surface area of potential docking sites and is also responsible for arborization
• Estrogen Maintains the interconnections of the brain and supports nerve growth, with increasing Synapse Formation After Neuronal Damage, induces nerve growth via induced release of different nerve growth factors in a complex feedback loop
• It increases Neuronal plasticity of the brain by regulating the formation and breakdown of synapses and branches through improved response to injury of strokes and by orchestrating abilities to turning on different genes.
• It Boosts NMDA Receptors

How Estrogen Affects Brain Function

• There are many functions attributed to Estrogens, some include
• It is a potent Activator and Performance Enhancer, also increasing Verbal Fluency and is a sensory booster.
• Estrogen Acts as an Activator and Performance Enhancer; Helps increase speed of limb-coordinated movements and enhances reaction time and short-term memory and boosts attention in monkeys while decreasing Distractibility
• Estrogen Boosts Attention to Tasks in Animals to make Neurons More Sensitive to Helpful Proteins.
• It is involved in Increases Verbal Fluency and Increases Performance and Speed of Learning in Rats

Additional Benefits of Estrogen

• Estrogen turns on but not all Progesterone receptors and boosts Neurotransmitter Response.
• Estrogen Is a Neuroprotector, increasing Blood Flow, Increases Glucose, and May Slow Atherosclerosis. Boosts Metabolic Activity and Improves Cardio vasular Health
• A 1996 study found a 54 percent reduction in those on Estrogen compared to women who hadn’t taken Estrogen over a decade
• A study confirmed a 40% Likelihood in Estrogen Women Versus Non, to ward off Alzheimer’s

Progesterone Effects on Memory and Neurons

• Progesterone, which is made in the brain, spinal cord, and peripheral nerves (from pregnenolone) may promote the formation of myelin sheaths.
• Progesterone's actions include stimulating release of dopamine in striatal tissue.
• Progesterone Stimulates the release of Gnrh From Hypothalamic Neurons and affects Modulates Oxytocin Receptor Binding in the Hypothalamus and inhibits Opioid Receptor Binding and effects the Potentiation of GABA and Also Directs the Incorporation of Steroids into the Cell

Testosterone Replacement For Memory

• It is thought that Testosterone May Protect the Memory of Healthy Aging Women while with proper balance, enough Estrogen is needed for them to properly stick properly.

Low Testosterone levels

• Testosterone levels in men decline at about 1% a year, starting about age 30.
• The effect increases so that testosterone levels are bioavailable, which decline quickly.
• This means the majority of men, 30-60%, hit Hypogonadal state in their 70s.
• Men with dementia can have a higher rate of mortality.
• The development of memory loss in males Is directly related to loss of testosterone during age.
• A lower level of testosterone can negatively alter Visual Memory.

Testosterone Therapy

• High levels indicate a better memory and cognitive function
• Men with prostate issues and a low testosterone count and taking hormones will respond to Verbal Memory, but not Spatial Performance
• It promotes Muscle Strength and a higher Libido.
• There is Improvement, but it is not apparent of Overall Cognative Improvement in men after treatment.

DHEA For Memory

• DHEA replacement therapy can Increase Muscle Strength and libido, as well as activates Immunity Function, improves wellness and has a positive effect on memory (for both men and women both the elderly
• Benefits may include less muscle soreness, improved Insulin, lowered Triglycerides, less Stress.
• In some cases where Alz had been diagnoised, Pregnenalome/ DHEA Levels had sunk in the cerebellum striatum
• Increased cortisol levels in the CSF in those afflicted, in those tests for AD.

Cortisol As It Retates to Memory

• Cortisol has a positive impact for critical memories,
• Stress might be a risk factor for Alz

Strategies

• Prolong the patient’s stress to deplete them of energy causing cognitive deficiency
• Make them increase nutrients
• The more emotional, the more likely to lose
• Increase or secrete epinephrine is going to cause memory loss.