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‫ﺼﺩﻕ ﺍﷲ ﺍﻟﻌﻅﻴﻡ‬
‫ﺍﻟﻨﻤل ﺍﻴﺔ ‪19 ‬‬
Hormonal Control of Brain
Development and Functions
By
Dr. Abdel Aziz Mohammed Hussein
Lecturer of Physiology
Mansoura Faculty of Medicine
Brain Facts Facts
•Brain weighs approximately 3
pounds (1400 gm in adults) •Brain controls ALL activities •Brain has approximately 100
billion neurons and 1 trillion
supporting cells
•Neurons can re-route circuits •Brain never stops adapting and
changing. •Neurons grow and organize
themselves into efficient
systems that operate a lifetime BRAIN STRUCTURES AND
FUNCTIONS
BRAIN STRUCTURES STRUCTURES
•• Frontal Lobe Lobe
•• Parietal Lobe Lobe
•• Temporal Lobe Lobe
•• Occipital Lobe Lobe
•• Cerebellum Cerebellum
•• Corpus Callosum Callosum
•• Brain Stem
BRAIN STRUCTURE FUNCTIONS FUNCTIONS
•Brain is an organ of
behavior—both overt
behavior and
consciousness are
manifestations of the
work of the brain •Different regions of
the brain regulate
different functions. •Our thoughts,
behaviors, and
emotions are the
result of how the
different parts of the
brain work together
to process
information and
BRAIN STRUCTURE FUNCTIONS
Brain Development
Brain Development Development
•At 1st the neural tube contains around 125,000 cells •At birth, the human brain contains around 100 billion neurons (rate is
250,000 per minute during the nine months of gestation)
Brain Development (cont.)
Brain Development (cont.) (cont.)
•Between the 7th prenatal month and a child’s first birthday, the brain
increased in weight by about 1.7 grams per day. •The weight of the brain of the newborn is approximately 300 grams (or
around 10% of body weight) •The adult brain weighs approximately 1400 grams (only 2% of body
weight)
Postnatal Growth of Brain •Brain weight increases with age and achieves 'adult' weight between 6th and 14th
years of life •Postnatal growth of the brain is due to;
1. an increase in the size of neurons
2.increase in number of supporting cells (glia)
3.development of neural processes and synapses (synaptogenesis)→ maximum
density between 6 and 12 months after birth.
4.laying down of the insulation of nerve processes (myelin sheaths).
Steps of Neuronal Development
Induction Induction
Production of cells that will become nervous tissue
become nervous tissue Proliferation Proliferation
Cell reproduction (mitosis)
Cell reproduction (mitosis) Migration Migration
Location of cells in appropriate brain areas
brain areas Differentiation Differentiation
Development of neurons into particular type
particular type Synaptogenesis Synaptogenesis Formation of appropriate synaptic connections
connections Selective cell
death death
Elimination of mislocated cells and cells that failed to form the proper synaptic connections
proper synaptic connections Functional
validation
(Pruning) (Pruning)
Strengthening of synapses in use, weakening of unused synapses
weakening of unused synapses Time Course of Critical Events in the Determination
of Human Brain Morphometery
Development of Brain Functions
Brain Maturation During Childhood and
Adolescence
Childhood
• Synaptic pruning strengthens connections • Synaptic pruning in the prefrontal Adolescence
• Synaptic pruning continues to improve memory & attention • Myelinization continues to protect neurons areas improves memory and where planning & other complex thinking attention. occurs. • Myelinization continues to protect • Brain hemispheres become specialized neurons & speed transmission of • Cortex matures signals • Fiber pathways that support speech & • New synapses may reflect learning through experience motor functions continue to mature • Fibers connecting language centers slow in growth rate • Analysis of emotional expressions matures
Adolescence and Brain Maturation Maturation
• Adolescence is a transitional period during
which a child is becoming, but is not yet, an
adult. •Normal adolescent development includes
conflict, facing insecurities, creating an
identity, mood swings, self-absorption, etc. •Underdevelopment of the frontal
lobe/prefrontal cortex and the limbic system
make adolescents more prone to “behave
emotionally or with ‘gut’ reactions”. •Adolescents tend to use an alternative part
of the brain– the amygdala (emotions) rather
than the prefrontal cortex (reasoning) to
process information. •Amygdala and nucleus acumbens (limbic
system within the prefrontal cortex) tend to
dominate the prefrontal cortex functions–
this results in a decrease in reasoned thinking
and an increase in impulsiveness.
Factors affecting Brain
Development and Functions
Factors affecting brain development and Functions
1) Genetic and environmental factors:
•
•
•
Genes and environment interact at every step of brain development, but they
play very different roles. Generally speaking, genes are responsible for the basic wiring plan—for
forming all of the cells (neurons) and general connections between different
brain regions while experience is responsible for fine-tuning those connections, helping each
child adapt to the particular environment (geographical, cultural, family,
school, peer-group) to which he belongs
2) Nutritional factors:
•Brain development is most sensitive to a baby's nutrition between mid-gestation
and two years of age. •Children who are malnourished--not just fussy eaters but truly deprived of
adequate calories and protein in their diet--throughout this period do not
adequately grow, either physically or mentally. •Their brains are smaller than normal, because of reduced dendritic growth,
reduced myelination, and the production of fewer glia (supporting cells in the
brain which continue to form after birth and are responsible for producing
Factors affecting brain development and Functions
3) Hormonal Control of Brain Development
The brain is a target organ for the actions of hormone secreted by the;
1.gonads,
2.adrenals, and
3.thyroid gland and
the sensitivity to hormones begins in embryonic life with the appearance of
hormone receptor sites in discrete populations of neurons.
Thyroid Hormones
◊ Sources of T3 and T4:
- T3 and T4 are detected in human coelomic and amniotic fluids as early as 8
weeks of gestation, before the onset of fetal thyroid function at 10-12 weeks.
- T3, an active form of TH, is produced locally by 5/ deiodination from T4, which
preferentially enters the developing brain than T3.
-Such preference is probably because brain –specific organic anion transporters
(Oatp1a4) at BBB, a major TH transporter at BBB preferentially binds to T4.
-After crossing to BBB, T4 taken by astrocytes and converted to T3 by type II
iodothyronine 5'-deiodinas.
- T3 is then transferred to neurons or oligodentrocytes through monocarboxylates
transporter 8 (MCT8) where it binds to TR receptors
Mechanism of Action of T3 and T4
A) Myelination of neurons e.g. myelin basic protein (MBP), proteolipid protein (Plp),
2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin associated
glycoprotein (MAG).
B) Dendritic structure or synaptogenesis e.g. RC3/neurogranin gene which has a role
in synapse formation and/or function and synaptotagmin-related gene 1 (Srg1)
which may also be involved in synapse formation and/or function.
C) Cell differentiation, migration and survival of neurons i.e. neurotophic factors e.g.
nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin
(NT) 3, and NT 4/5.
Role of thyroid hormones in Bain development
(1) Early embryonic brain development: (a) No effects on neural induction, neurulation, and establishment and polarity and segmentation
(2) Cell migration and the formation of layers: (a) Cerebral cortex: contributes to the right position of neocortical neurons and distribution of callosal connections (b) Cerebellum: controls the rate of migration of granular cells from the external germinal layer to the internal granular layer.
(3) Neuronal and glial cell differentiation: (a) Specific neuronal types: (i) Controls dendritic development and number of dendritic spines of pyramidal cells of neocortex and hippocampus. Dendritic spines are important in synaptic plasticity (ii) Influences differentiation of cholinergic cells of brain stem and forebrain (iii) Maturation of dendritic arborization of Purkinje cells: in the absence of thyroid hormone, Purkinje cells have elongated primary dendrite, reduced dendritic arborization and persistence of transient axo­somatic connections (b) Oligodendrocyte differentiation: (i) T3 is an instructive factor for oligodendrocyte differentiation from stem cells Glucocorticoid and Brain Development and
Functions
-Glucocorticoid administration to rats at birth delays eye opening, inhibits
dendritic development and myelination, and delays appearance of
pituitary-adrenal rhythmicity.
-acute and chronic stress paradigms decrease the expression of brainderived neurotrophic factor (BDNF) in the hippocampus
-Glucocorticoid hormones have been shown to augment dopaminergic
neuronal function at many levels
-prenatal stress causes an increase in the turnover of norepinephrine in the
cortex and locus coeruleus and increases serotonin synthesis in fetal
brain as well as concentrations of the brainstem serotonin transporter in
rats.
-Cortisol increases the tendency for insomnia and reduction in the total
time in rapid eye movement (REM) sleep. Also glucocorticoids tend to
increase intermittent wakefulness and increase the slow wave sleep
(SWS) time.
Sex Hormones and Sexual (Dimorphism) Differentiation
of Brain
Sexual differentiation:
Male:
– Testosterone secreted into the blood reaches the brain
– testosterone converted to estradiol and dihydrotestosterone in the brain
– estradiol masculinizes the brain
Female:
– placenta protect female from testosterone by aromatase that converts it into
estradiol
– alpha-fetoprotein binds to estradiol → prevents estradiol from entering the brain
– protects female brains from being masculinized by estradiol
Different Brain Regions that show Sexual Dimorphism
Neocortex •Primary motor cortex, Sensorimotor cortex, Visual cortex •Accessory olfactory bulb •Bed nucleus of the stria terminalis •Amygdaloid nucleus •Hippocampus and dentate gyms •Anterior commissure •Corpus callosum Mesencephalon •Substantia nigra Rhombencephalon •Locus coeruleus Spinal cord •Intermediolateral nucleus Diencephalon •Preoptic area •AVPN­POA •SDN­POA •Hypothalarnus •Interstitial nucleus of the anterior hypothalamus •Suprachiasmatic nucleus •Supraoptic nucleus •Ventromediai nucleus •Arcuate nucleus •Massa intermedia Peripheral nervous system •Superior cervical ganglion •Pelvic ganglion •Hypogastric ganglion
•Spinal nucleus of bulbocavernosus
(SNB) Sexual Development of Brain
—
Prenatal hormone exposure fundamentally organizes
the brain:
◦ Sexual/Reproductive Behaviors:
– development of the hypothalamus (sexual orientation)
◦ Problem Solving
◦ Aggression
◦ Rough-and-tumble play
Sex Differences
—
Men:
◦
◦
◦
◦
—
spatial rotation tasks
mathematical reasoning tasks
navigation through a route
guiding or intercepting projectiles
Women:
◦ perceptual speed - rapidly identifying matching
items
◦ mathematical calculation tasks
◦ greater verbal fluency
◦ recalling landmarks from a route
◦ faster at precision manual tasks
Sex Differences
Hemisphere Differentiation
right hemisphere involved in spatial functions
left hemisphere involved in language
-female brains had larger corpus callosum
-women have larger corpus callosum
-size of corpus callosum positively correlated with
cognitive skills in women, but not men
-males showed greater asymmetry than females
-right hemisphere thicker in males than females
Sex Differences
—
—
◦ Sex differences in auditory system
Females:
– greater hearing sensitivity
– Greater susceptibility to noise exposure at high
freq.
Males:
– better sound localization
– detecting binaural beats
– detecting signals in complex masking taks
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Abdel Aziz Hussein, Mansoura University, Mansoura, Egypt