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Homeostasis 2
Árpád Dobolyi
Laboratory of Molecular and Systems Neurobiology,
Department of Physiology and Neurobiology, Eötvös
Loránd University
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Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
– Body temperature regulation
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The brain in midsagittal section
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Neuronal cell bodies and fibers form the gray and
white matter of the nervous tissue, respectively
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Organization of the gray matter
Similar neurons next to each other often form plain layers (e.g. cerebral and
cerebellar cortex) or roundish to irregular-shaped nuclei (e.g. basal ganglia,
thalamus) in the central nervous system.
Cerebral cortex Thalamus
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Cell types in the nervous tissue
• Nerve cells or neuron(e)s
– excitable cells with long processes
• Glial cells
– non-excitable cells with short processes
• Additional cells
– cells of blood vessels and connective tissues
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Glial cells in the central nervous system
• Astrocytes– Support neurones metabologically
• Oligodendrocytes– Form the myelin sheath around axons
• Microglia– Immune protection of
the CNS
• Ependymal cells– Form the borders of the ventricles
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The neuron
• Many different types
• Compartmentalized
Neuronal process =
= axon or dendrite
Neurite = axon (sometimes it
is meant neuronal process)
Nerve fiber = axon together
with its myelin sheath
• Polarized
• Excitable
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Basic functions of different parts of neurones
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Different morphological types of neurons
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Types of CNS neurones based on their targets
(Golgi II neuron)(Golgi I neuron)
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Axon terminals contact other neurons and muscles usingchemical synapses
• The word synapse was introduced by Charles Sherrington around 1900
• Chemical transmission was suggested by Henry Dale in 1930s:
There is no continuity between the cytoplasms of neurones but rather
chemical compounds released from vesicles transfer the information
between them
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Glutamate is the major excitatory transmitter in chemicalsynapses of the central nervous system
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• Consist of 3-50 amino acids
• Bioactive substances with neuromodulator function
• They are synthesized as prepropeptide and process through posttranslational modifications
• They are transported in axons towards the presynaptic terminal by vesicular transport
• They are released by regulated vesicular secretion
• Neuropeptides possess high-affinity G-protein coupled, 7TM cell surface receptors
Definition and characteristics of
neuropeptide hormones
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Synthesis of neuropeptides
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Axonal transport of neuropeptides
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Storage of neuropeptides in presynaptic terminals
Peptides are stored in „large dense core vesicles” (LDCVs) and not in „small clear vesicles” (SCVs)
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Large dense core vesicles in presynaptic terminals
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Release of neuropeptides following neuronal activity
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G-protein coupled peptide receptors
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Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
– Body temperature regulation
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Homeostatic center of the brain:
the hypothalamus
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Regulatory functions of hypothalamic nuclei
• Vegetative regulations (e.g. heart frequency)
• Neuroendocrine regulations (e.g. stress response)
• Salt and water balance
• Food intake and body weight
• Temperature
• Circadian rhythms
• Sleep
• Reproduction
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• Thalamus
• Epithalamus– Habenula
– Habenular nuclei
– Stria medullaris
– Trigonum habenulae
– Habenular commissure
– Pineal body
• Metathalamus– Medial geniculate body
– Lateral geniculate body
• Subthalamus– Subthalamic nucleus
– Zona incerta
– H fields of Forel
• Hypothalamus
The hypothalamus, a part of the diencephalon
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Medio-lateral zones of the hypothalamus
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Antero-posterior regions of the hypothalamus
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The distribution of GnRH-producing neurons in the preoptic area of the hypothalamus
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Example of a reproductive regulation:GnRH neurons in the preoptic area of the hypothalamus
control estrogen levels
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KISS I neurons mediate the homestatic status of the body to GnRH neurons
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The distribution of kisspeptin-producing Kiss1 neurons in the preoptic area
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Other homeostatic functions of the preoptic
region of the hypothalamus
•: Position of neurons participating in the control of body temperature
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Hypothalamic centers of sleep regulation:
1. ´sleep on´ cells in the VLPO
VLPO: ventrolateral preoptic nucleus
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Anterior hypothalamic region
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The paraventricular hypothalamic nucleus
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Corticotropin-releasing hormon (CRH)-containing neurons in the paraventricular hypothalamic
nucleus (PVN)
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The distribution of oxytocin and vasopressinneurons in the hypothalamus
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hypothalamus
pituitary
(anterior lobe)
capillary
bed
endocrine
cell
blood flow
blood
flow
capillary
bed
pituitary
(posterior lobe)
Oxytocin and ADH
(blue triangles) are
secreted into the blood
via capillaries in the
posterior pituitary
Endocrine cells of the
anterior pituitary secrete
hormones (red squares)
in response to releasing
hormones; the pituitary
hormones enter the
bloodstream
Neurosecretory cells of
the hypothalamus produce
oxytocin and ADH
Releasing or inhibiting hormones
(green circles) are secreted into
capillaries feeding the anterior lobe
of the pituitary
Neurosecretory cells
of the hypothalamus
produce releasing and
inhibiting hormones
1
2
1
2
3
Secretory activity of the pituitary
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Role of the pituitary
• The posterior pituitary receives oxytocin or antidiuretic hormone (ADH) from the hypothalamus, relays them to the body as necessary.
• The anterior lobe of the pituitary receives signals from the hypothalamus, and responds by sending out the appropriate hormone to other endocrine glands.
The anterior lobe of the pituitary is the “master gland” that signals other glands to produce their hormones when needed.
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Pituitary hormones
Pituitary Hormone Functions
Follicle-stimulating
hormone
Stimulates maturation of egg in the ovary and release of sex
hormones.
Lutenizing hormone Stimulates maturation of egg and of the corpus luteum
surrounding the egg and release of sex hormones.
Thyroid-stimulating
hormone
Stimulates the thyroid to release thyroxine.
Adrenocorticotropic
hormone
Causes the adrenal gland to release cortisol.
Melanocyte-stimulating
hormone
Stimulates synthesis of skin pigments.
Growth hormone Stimulates growth during infancy and puberty.
Antidiuretic hormone Signals the kidney to conserve more water.
Oxytocin Affects childbirth, lactation, and some behaviors.
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CRH
GH-RH
LH-RH
SOM
Neuroendocrine regulatory hypothalamic nuclei
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Anterior hypothalamic region
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Circadial regulation of neural functions
PACEMAKER: SUPRACHIASMATIC NUCLEUS (SCN)
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Principle of creating circadian (daily) rhythms
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Antero-posterior regions of the hypothalamus
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Tuberal and posterior hypothalamic regions
Tuberal hypothalamic region Posterior hypothalamic region
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Hypothalamic centers that control food
intake and body weight
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Location of orexin neurons in the lateral hypothalamic area
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Major pathways
regulating food
intake
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Circumventricular organs – humoral inputs
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Neuronal inputs to the hypothalamus
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Extrahypothalamic projections of hypothalamic nuclei
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Hypothalamo-spinal tract and other
descending pathways regulating vegetative
functions
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Neural elements of homeostatic regulations
NTS: nucleus of the solitary tract, PBN: parabrachial nucleus, RF: reticular formation,
DMX: dorsal motor vagus nucleus, ILN: intermediolateral column (nucleus) of the spinal cord
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Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
– Body temperature regulation
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Water balance of the body
Uptake (ml) Loss (ml)
As fluid: 1000-1500
As food: 700
From metabolism
(mainly oxidation of
carbohydrates) : 300
Urine (kidney):
1000-1500
Skin-lung: perspiration
insensibilis: 900
Faces: 100
Total: 2000-2500 Total: 2000-2500
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Regulation of water balance
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Hypothalamic centers regulating water
balance
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Function of plasma ADH concentration on
osmolarity and volume of blood
Remark: thirst increases only above 290 mOsm at normal blood volume
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Nephron,
the functional
unit of kidney
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The effect of ADH (antidiuretic hormone,
vasopressin) on the cells of the collecting duct
V2 type receptors of ADH is present in the cells of the collecting duct of the renaltube. Their activation leads to the increase of cAMP, which in turn activates
protein kinase A, whose final effect is that water channels (aquaporines) get tothe apical membrane of the cells, which therefore becomes water-permeable.
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Regulation of water balance
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Regulation of water uptake
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Regulatory pathways of thirst
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Brain areas activated by thirst
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Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
– Body temperature regulation
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Heat produced by basal metabolism
Energy produced by basal metablism leaves the body in the
form of heat. It depends on th size of the animals:
- Heat produced by bigger animals is larger
- Heat produced per body weight decreases with the size of
the animal
Rubner’s surface area law: heat produced by the basal
metabolism of animals is proportional with their surface area
rather than their body weight.
More precisely: Heat produced by basal metabolism is
proportional to W0,75 , where W is the body weight. Thus, heat
production is 290 KJ/W0,75, and does not depend on individual
or the species.
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Factors determining heat balance of animals
Animals with
constant body
temperature thrive for
heat balance:
Heat loss =
heat taken from the
environment + heat
produced by the body
Red color:
controllability
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1. In response to small alterations from set point body temperature, animals first change the circulation of the skin:
• If ambient temperature decreases, skin arterioles contract thereby decreasing heat dissipation
• If ambient temperature increases, skin arterioles dilatate thereby increasing heat dissipation
Body temperature control 1.
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In response to larger alterations from set point body temperature:
A. In cold environment
• Heat production by the brown adipose tissue is activated
• Muscle contraction can further increase heat production
(shivering)
• Activation of thyroid hormone production increases metabolism
by enhancing cellular oxidation
• Appropriate behavioral changes
B. In warm environment
• Enhanced ventillation of the lung
• Sweating starts, water evaporates from the skin
• Appropriate behavioral changes
Body temperature control 2.
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Mechanism of heat production in brown adipose tissue
If the inner membrane of mitochondrium leaks H-ions then heat is produced instead of ATP
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If previous measures were inefficient and body
temperature alteration is life-threatening:
A. In cold environment
• Due to the activation of stress axis, cellular metabolism is
further increased
B. In hot environment
• Heart frequency and blood circulation increases
Body temperature control 3.
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Slower adaptations to changes of long-time
alterations of ambient temperature:
1. Alterations of thermal insulation:
- adiposity depos build up
- Changes of outer integument
(e.g. seasonal changes of hair, feather)
2. Appropriate behavioral changes
Body temperature control 4.
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Temperature receptors: transients receptor potential (TRP) channels
Etain A. Tansey, and Christopher D. Johnson Advan in Physiol Edu 2015;39:139-148.
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Temperature receptors (TRP channels) are located
on free (or bare) nerve terminals in the skin
Thin myelinated (Aδ) or
unmyelinated axons (C)
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A
C
AA
A termosensitive (cold) fibers
termination: lamina I
lamina IIa
lamina V
C termosensitive (warm) fibers
termination : lamina IIb
Termination of heat-
sensitive primary
afferents in the
spinal cord
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Pathways of heat sensation and heat
localization (only ascending)
- spinothalamic tract
- trigeminothalamic tract
Thermoregulatory pathways
- ascending and descending
Pathways of thermal stress (only descending)
Neuronal pathways carrying temperature
information
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The ventral
posterolateral
nucleus of the
thalamus (VPL)
relays sensory
inputs from the
body to the
cerebral cortex
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Somatotopy in the VPM/VPL
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Thermoregulatory
pathways
DH: dorsal horn of spinal cord
LPB: lateral parabrachial nucleus
POA: preoptikus terület
MnPO: median preoptic nucleus
MPA: medial preoptic area
CVC: cutaneous vasoconstrictor
W-S: warm-sensitive
DMH: dorsomedial hypothalamic nucleus
rRPA: rostral raphe pallidus
VH: ventral horn of spinal cord
IML: intermediolateral cell column
BAT: brown adipose tissue
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Lateral parabrachial nucleus (LPBN)
scp: superior cerebellar peduncle = brachium superior
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Heat-sensitive neurons in the preoptic region of the hypothalamus
•: Cells reacting to central and peripheral change of temperature
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Summation of peripheral and central input on heat-
sensitive neurons of the medial preoptic area
a, b: activation of peripheral warm-sensitive receptors
c-d: activation of central warm-sensitive receptors
e: activation of central cold-sensitive receptors
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Thermoregulatory
patyways
DH: dorsal horn of spinal cord
LPB: lateral parabrachial nucleus
POA: preoptikus terület
MnPO: median preoptic nucleus
MPA: medial preoptic area
CVC: cutaneous vasoconstrictor
W-S: warm-sensitive
DMH: dorsomedial hypothalamic nucleus
rRPA: rostral raphe pallidus
VH: ventral horn of spinal cord
IML: intermediolateral cell column
BAT: brown adipose tissue
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Location of the dorsomedial nucleus in the
hypothalamus and the raphe pallidus in the medulla
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In response to larger alterations from set point body temperature:
A. In cold environment
• Heat production by the brown adipose tissue is activated
• Muscle contraction can further increase heat production
(shivering)
• Activation of thyroid hormone production increases metabolism
by enhancing cellular oxidation
• Appropriate behavioral changes
B. In warm environment – neuronal pathways are not known
• Enhanced ventillation of the lung
• Sweating starts, water evaporates from the skin
• Appropriate behavioral changes
Body temperature control 2.
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Neuroendocrin and
descending
thermoregulatoy
pathways controlling
the secretion of
thyroid hormones
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If previous measures were inefficient and body
temperature alteration is life-threatening:
A. In cold environment
• Due to the activation of stress axis, cellular metabolism is
further increased
B. In hot environment
• Heart frequency and blood circulation increases
Body temperature control 3.
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Pathways of heat
stress
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Thank you for your
attention!
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Endocrine Hormones
Gland Hormones Functions
Thyroid Thyroxine Regulates metabolism
Calcitonin Inhibits release of calcium from the bones
Parathyroids Parathyroid hormone Stimulates the release of calcium from the bones.
Islet cells (in
the pancreas)
Insulin Decreases blood sugar by promoting uptake of glucose by cells.
Glucagon Increases blood sugar by stimulating breakdown of glycogen in the liver.
Testes Testosterone Regulates sperm cell production and secondary sex characteristics.
Ovaries Estrogen Stimulates egg maturation, controls secondary sex characteristics.
Progesterone Prepares the uterus to receive a fertilized egg.
Adrenal cortex Epinephrine Stimulates “fight or flight” response.
Adrenal
medulla
Glucocorticoids Part of stress response, increase blood glucose levels and decrease
immune response.
Aldosterone Regulates sodium content in the blood.
Testosterone (in both
sexes)
Adult body form (greater muscle mass), libido.
Pineal gland Melatonin Sleep cycles, reproductive cycles in many mammals.