Hormones play a significant role in cognition and brain function. Imbalances in hormones like cortisol, DHEA, estrogen, melatonin, pregnenolone, testosterone, thyroid, and vasopressin can cause memory loss, poor concentration, and confusion due to their effects on neurotransmission, brain structure, and gene expression. Specific hormones like estrogen, pregnenolone, testosterone, and thyroid influence cognition and memory in different ways such as promoting neurogenesis, regulating neurotransmitters, and ensuring proper blood flow and oxygen to the brain. Pregnenolone in particular plays an important role in forming memories by activating NMDA receptors independently of glutamate.

1. Presented by
S.Shruthi
LS1267

3. Cognition:
Includes memory, and is “a general term that refers to
the ability to know, which includes all types of perceiving,
recognizing, thinking, learning, reasoning, problem solving,
imagining, mental clarity, and the ability to concentrate and
focus.” Cognition also includes verbal memory, visual/spatial
memory, speech and language skills, and higher-order
intellectual thinking.

7. A hormone imbalance can wreak havoc on brain chemistry
and communication between brain cells (i.e.,
neurotransmission)
In fact, concentrations of the estrogens, progesterone,
pregnenolone, testosterone, DHEA
(Dehydroepiandrosterone)and other hormones can be higher
in the brain than in the bloodstream. Research indicates that
nerve cells in the brain (and central nervous system) are
actually producing their own supply of these hormones (i.e.,
“neuro-steroids”), independently of hormone production by
the ovaries, testes and adrenal glands.
Because hormones are often more concentrated in the brain,
any hormone imbalance can affect brain function
dramatically.

8. Deficiencies in cortisol, DHEA, estrogen hormones,
melatonin, pregnenolone, testosterone, thyroid, and
vasopressin exhibit the most common brain-related
symptoms, including memory loss, poor concentration, and
confusion.
Chronic medical conditions, especially those linked with a
hormone imbalance, typically also have a profound impact on
brain health and often lead to memory problems. Conditions
commonly associated with memory loss are depression,
arteriosclerosis, blood sugar problems, chronic fatigue
syndrome, fibromyalgia, allergies, and infections such as
candida—all of which are also often associated with a
hormone imbalance.

9. In the brain, hormones alter the production of gene
products that participate in synaptic neurotransmission as
well as affect the structure of brain cells. As a result, the
circuitry of the brain and its capacity for neurotransmission
are changed over a course of hours to days. In this way, the
brain adjusts its performance and control of behavior in
response to a changing environment.
Sexual differentiation of the brain is caused by sex
hormones acting in fetal and early postnatal life, although
recent evidence suggests genes on either the X or Y
chromosome may also contribute to this process. Scientists
have found statistically and biologically significant
differences between the brains of men and women that are
similar to sex differences found in experimental animals.

10. These include differences in the size and shape of brain
structures in the hypothalamus and the arrangement of
neurons in the cortex and hippocampus. Sex differences go
well beyond sexual behavior and reproduction and affect many
brain regions and functions, ranging from mechanisms for
perceiving pain and dealing with stress to strategies for solving
cognitive problems.
Dementia (sometimes referred to as senility) is the gradual
deterioration of cognition such that it interferes with daily
living. It is caused by diseases that affect the brain, and is not
necessarily the outcome of aging. Dementia can influence all
aspects of mind and behavior, including memory, judgement,
language, concentration, visual perception, temperament, and
social interactions.

12. Estrogens
The estrogen hormones—primarily estrone, estradiol (the most
abundant) and estriol— “the brain is a major target organ of estrogen,” so it
is no surprise that the estrogens have such profound effects on brain health,
in both men and women, including:
 Promoting networking between brain cells by increasing the
number of dendritic branches, and keeping them strong and well-defined,
which also increases the number of potential synapses.
 Increasing levels of the mood-regulating neurotransmitters,
including acetylcholine, serotonin, and noradrenaline.
 Increasing the density of neurotransmitter receptors, thereby
promoting better neurotransmission and mental well-being.
 Maintaining nerve cell health by encouraging nerve growth and
preventing the accumulation of free radicals.
 Helping to prevent brain damage by reducing inflammation and
promoting brain cell repair when damage occurs.
 Promoting brain vibrancy by increasing blood flow to the brain,
which increases the oxygen and glucose available.

13. This effect can be explained by the modulatory role of estrogen on several
neurotransmitter systems, such as acetylcholine, catecholamines, serotonin
and GABA(gamma-aminobutyric acid), in both animals and
humans.Another reason may lie in the widespread presence of estrogen
receptors detected in many regions involved in cognitive processes, such as
learning and memory, including the hippocampal formation (HF), amygdala
and cerebral cortex
The hormonal influences on motor activity involve brain areas such as the
nucleus accumbens, striatum, substantia nigra and ventral tegmental area,
while the effects on memory processes imply actions on brain structures
such as the basal forebrain and HF, and those on mood involve, at least in
part, the serotonergic system of the midbrain raphe nuclei.

14. Testosterone
Certain hormones, such as testosterone, may also influence our ability to
perform different types of thinking tasks.
Without enough testosterone the arteries in the brain weaken, growing too
soft in some places (increasing the risk of blood clots and stroke) and too
stiff in others (increasing the risk of high blood pressure and cerebral
hemorrhage)—none of which is good for the memory! When the arteries of
the brain wear out, blood can no longer properly circulate there or to any
organ. When the resulting lack of oxygen and nutrients to the brain is
chronic, memory weakens.”
Among humans, age-related decline in testosterone is associated with
declining cognitive functioning, and aging men with higher testosterone
maintain better cognitive performance.

15. Thyroid
Thyroid hormones also have significant effects on thought processes and
memory. “In the brain’s gray matter, where thinking takes place, the blood
begins to flow more slowly as thyroid levels decline. As a result, less oxygen
and fewer nutrients reach the brain cells, the brain becomes malnourished,
and the brain’s owner thinks and moves less. … Without enough thyroid
hormones, the number of connections (dendrites and synapses) between the
brain cells decreases, weakening the brain cells.”
Without enough thyroid hormones, the number of connections (dendrites
and synapses) between the brain cells decreases, weakening the brain cells.”

16. Pregnenolone
Pregnenolone is the first hormone in the pathway that generates a host
of key neurohormones in the brain that are known to affect nerve cell
growth and to modulate various moods
 Pregnenolone “the memory hormone” because of its astounding ability
to improve memory. Research has shown that pregnenolone works as a
neurotransmitter to clarify thinking, promote concentration, and prevent
memory loss. One of its more unusual effects, according to some patients,
is that it seems to intensify color perception.
 Pregnenolone is the most abundant hormone in the brain, and is
concentrated about 75 times greater in the brain than in the blood. It
serves as a precursor to many of the other hormones, so even a slight
deficiency can have a domino effect on other hormones.

17.  Most memory formation occurs as the result of stimulation of nerve cells.
Stimulation generally results in the production of nerve branches known as
dendrites, which connect to additional neurons, making the entire
“switchboard” larger and more complex. These structures are formed by
activating special “switches” in the brain.
While there are a variety of such excitatory switches, the category called
NMDA (N-methyl-D-aspartate) channels (or receptors) comprises the most
important group. These channels must be activated for learning and
memory to occur.
 The typical excitatory brain chemical that activates those memory-
enhancing NMDA receptors is the amino acid glutamate, which is present
throughout the brain.And while glutamate is critical for normal learning,
too much excitation by glutamate over time can damage neurons—in fact,
overstimulation, or excitotoxicity, by glutamate is thought to be one of the
underlying factors in neurodegenerative disorders such as Alzheimer’s
disease

18. What makes
pregnenolone so
important ?????????

19.  In this context pregnenolone seems to trigger the NMDA channels
through a mechanism that is independent of glutamate, which in turn may
account for the observed neuroprotective effects of pregnenolone on brain
cells.
 The bottom line of all this intricate science is that pregnenolone may play
a pivotal role both in laying down memories in the first place, and then
preventing their loss by directly protecting the nerve networks that store
them!

20. DHEA (dehydroepiandrosterone)
It has a technical-sounding name because it has never been identified
with a single dominant function, in spite of its abundance in the body.
Many researchers still think of it as a substance produced by the adrenal
glands, but experiments show that animals without adrenals are able to
produce it in normal amounts. Much of it is formed in the brain (from
pregnenolone), but it is probably produced in other organs, including the
skin. The brain contains a much higher concentration of DHEA than the
blood does.
One study has found that the only hormone abnormality in a groupt of
Alzheimers patients' brains was an excess of DHEA. In cell culture,
DHEA can cause changes in glial cells resembling those seen in the aging
brain. These observations suggest that DHEA should be used with
caution. Supplements of pregnenolone and thyroid seem to be the
safest way to optimize DHEA production.

21. Protection against the toxic actions of these
specialized hormones is a major function of DHEA
and the other youth-associated hormones.

23. How is stress communicated from mom to fetus?
Response to stress involves a number of organs and systems within the
body; from the brain to specialized organs, such the adrenal glands,
which are adjacent to the kidneys.
The process begins with a stressor stimulating the brain, which
evaluates the threat and processes it into an appropriate response,
physiological and behavioural. This results in the secretion of corticoids,
such as cortisol, and glucocorticoids from the adrenal glands into the
bloodstream. The corticoids are molecules, which trigger the “flight or
fight” response of an individual to stress

25. When is a fetus most susceptible to prenatal maternal
stress?
Two periods are especially crucial :
At week 10, the embryo becomes a fetus and it begins to move. The vital
organs now have a solid foundation. During this time, the brain will
produce almost 250,000 new neurons every minute. This is called
neurogenesis
During weeks 24 and 30, nerve cell connections are occurring. Guided by
chemical signals, nerve processes seek out their target and establish
contact. Communication between neurons begins. At birth, there are an
excess of nerve connections, those that are not used will degenerate. This is
called synaptogenesis

26.  It seems that stress can actually affect the microbes that reside in an
expectant mother's vagina, which, in turn, are transferred to the newborn
during vaginal birth, resulting in changes to the little one's gut
microbiome and brain development.
 As a result, these changes have an impact on the infant's immune
system and metabolism. In fact, scientists believe that the altered gut
microbiota is linked to a greater risk of neurodevelopmental disorders,
including autism and schizophrenia.

30.  Many recent human research findings have shown that acute prenatal
stress affects children’s cognition – or ability to think. These studies involve
evaluating the mothers’ stress levels during pregnancy and following their
children as they grow. To determine the children’s cognitive abilities, tests
are administered which determine their intellectual and language skills.
A study conducted by the Douglas Institute monitored pregnant women
and their children during and following a severe ice storm. The children
exposed to high levels of objective prenatal stress, exhibited poorer
cognitive and linguistic abilities relative to the children exposed to low
levels.
Effects on cognition

31. A study conducted in The Netherlands correlated prenatal stress with
infant performance at three and eight months. Their findings showed
that mothers who had high levels of the stress hormone, cortisol, during
mid-pregnancy, had children who scored lower on cognitive tests relative
to their peers. This effect was more obvious for the older children than
the younger.
A study conducted in Rochester, NY, evaluated mothers who were
admitted to a clinic serving high-risk patients. This study showed that
stress or anxiety in pregnancy is associated with increased cortisol in the
mother. In addition the researchers suggested that this prenatal
exposure to cortisol predicts a lower cognitive ability at 17 months

32. The effects of maternal stress and anxiety
during pregnancy
Since ancient times, scientists have written about beliefs that the
emotional state of the pregnant mother may affect her unborn child.
Today, both animal and human studies support the notion that maternal
stress and anxiety during pregnancy can have both immediate and long-
term effects on her offspring.

33. Oxytocin: Normal Physiology
 Oxytocin is a powerful reproductive hormone with widespread effects on
the brain and body of all mammals, for example, by mediating sperm
ejection, labor contractions, and milk ejection.
 Oxytocin also reduces stress by centrally activating the parasympathetic
nervous system, which promotes calm,connection, healing, and growth; and
by reducing activity in the sympathetic nervous system, which
reduces fear, stress, and stress hormones, and increases sociability.
 Oxytocin has a short half-life, but its effects can be prolonged because it
modulates other brain-hormone systems (neuromodulation).

34. Beta-Endorphins: Normal Physiology
Beta-endorphins are endogenous opioids that give analgesic and adaptive
responses to stress and pain.Beta-endorphins also activate brain reward
and pleasure centers, motivating and rewarding reproduc-
tive and social behaviors, and support immune function, physical activity,
and psychological well-being.
From labor through the postpartum period, beta-endorphins promote:
 endogenous analgesia though prelabor increase in central receptors
(animal studies) and increases in beta-endorphins as labor progresses
 an altered state of consciousness that may help with labor stress and
pain
 fetal neuroprotection from hypoxia (animal studies)
 postpartum peaks of beta-endorphins (along with oxytocin) that may
facilitate maternal euphoria and prime reward centers, imprinting
pleasure with infant contact and care
 reward and reinforcement of breastfeeding in both mother and baby
 newborn support with the stress of postpartum transition, including via
beta-endorphins in colostrum

35. Epinephrine-Norepinephrine and Related Stress Hormones:
Normal Physiology
 Epinephrine (adrenaline) and norepinephrine (noradrenaline) mediate
“fight or flight” stress responses.
 Epinephrine-norepinephrine release with perceived danger has
promoted safety for laboring females in the wild through human evolution
by:
 slowing or stopping labor, giving time for fight or flight
 redistributing blood to heart, lungs, and major muscle groups, and away
from uterus and baby, to maximize fight-or-flight actions

36. Prolactin: Normal Physiology
 Prolactin is a major hormone of reproduction as well as breast-milk
synthesis. Prolactin adapts maternal physiology for pregnancy and
breastfeeding, promotes maternal adaptations, and is a caregiving hor-
mone in mammalian mothers and fathers. Outside of reproduction, it is a
stress and growth hormone.
 Maternal prolactin elevations from early pregnancy may have stress-
reducing effects that also benefit the fetus. Late-pregnancy prolactin
elevations promote the formation of prolactin receptors in the brain and
mammary gland (animal studies).
 Near term, prolactin production also increases in the uterine lining
(decidua), and may be involved in labor processes. Prolactin in amniotic
fluid, which fills the fetal lungs, may assist with respiratory preparations.
Fetal prolactic production increases close to the physiologic onset of labor,
and may promote newborn transitions.

37. The Effects of Prenatal Stress on Child Behavioural and Cognitive
Outcomes Start at the Beginning
Vivette Glover, MA, PhD, DSc
Institute of Reproductive and Developmental Biology, Imperial College London,
United Kingdom
January 2011
 DiPietro, J.A. (2004). The role of maternal stress in child development.
Current Directions in Psychological Science
 Enhancing Cognitive Function with Pregnenolone
November 2007 By Julius G. Goepp, MD
 Progesterone Pregnenolone & DHEA - Three Youth-Associated Hormones
PROGESTERONE INFORMATION
Raymond Peat, MA, PhD (Univ. of Oregon)
REFERENCES:

38.  Connectionsis a publication of Women’s International Pharmacy which is dedicated
to the education and management of PMS, menopause, infertility, postpartum
depression, and other hormone-related conditions and therapies.
 L. M. Glynn, C. A. Sandman. Prenatal Origins of Neurological Development: A
Critical Period for Fetus and Mother. Current Directions in Psychological Science,
2011; 20 (6): 384 DOI: 10.1177/0963721411422056