Tues 1012

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Tues 10/12
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Adverse Outcome Due to Prenatal Rubella (From
Alford, Pass, and Stagno, 1983) 30 of infants
are symptomatic at birth Heart
Defects Microcephaly Deafness Growth
Retardation Retinopathy Cataracts
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Rubella continued Of those symptomatic at birth,
80 show neurobehavioral problems in
childhood Hearing loss Language
disorders Visual abnorm. Motor
disorders Hormonal abnorm. Cognitive
dysfunction Dental Defects Emotional disorders
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Rubella continued Of the 70 of infants who are
not symptomatic at birth, 70 show Hearing
loss Language disorders Visual abnorm. Motor
disorders Hormonal abnorm. Cognitive
dysfunction Dental defects Emotional disorders
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Teratogenic Effects of Radiation

• Mental retardation
• Highest risk during major neuronal migration, at
  8-15 weeks. Incidence increases with dose. At 1
  Gy fetal dose, 75 experience severe retardation
• At 16-25 weeks, fetus shows no increase in mental
  retardation at doses lt 0.5 Gy
• IQ - Risk factor associated with diminution of IQ
  is 21-33 points at 1 Gy to fetus on 8-15 weeks.
• Microcephaly
• observed in 30 children of 1000 exposed in
  Hiroshima and Nagasaki pregnant women
• the effect lt0.3 Gy is not significantly
  different from control

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• Accutane pill used to treat cystic acne
• a synthetic Vitamin A (a retinoic acid)
• isotretinoin

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• Accutane interferes with the development of
• Central Nervous System
• Craniofacial structures
• The Heart
• The Thymus and Parathyroid Glands
• Other organ systems

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• Embryonic Exposure to Accutane (Isotretinoin)
• Spontaneous Abortion (40)
• Major Malformations (35)
• Prematurity 16

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• CNS Abnormalities
• Cerebellar Hypoplasia (small cerebellum)
• Absence or Reduced Size of the Cerebellar
  Vermis (a part of the cerebellum)
• Ventriculomegaly (4th) enlargement of the 4th
  ventricle
• Cranial Nerve Abnormalities (optic oculomotor)

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• Additional CNS Abnormalities (visible on
  autopsy Lammer and Armstrong, 1991)
• Pons
• Medulla
• Thalamus
• Hippocampus
• Heterotopias in Frontal Cortex
• reduced myelination

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Figure 1. Mental ability of children exposed to
isotretinoin during embryonic development.
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• Is vulnerability to the CNS effects of retinoic
  acid seen in adolescence?
• controversial human data suggest that some
  individuals of unspecified ages may experience
  depression, suicidality, or psychosis following
  Accutane treatment (Wysowski, Pitts, and Beitz,
  2001 Bremner, 2003)
• long term effects are unknown
• 2 studies in adolescent mice show that 21 days
  of treatment with 1 mg/kg/day 13 cis RA reduces
  hippocampal cell survival (Sakai et al, 2004) and
  reduces spatial learning (Crandall et al, 2004)
• reduced hippocampal neurogenesis has been shown
  in depression (increased during antidepressant
  treatment)

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• Prenatal Exposure to Anticonvulsant Medications
• Major malformations
• Craniofacial Abnormalities
• Digit Hypoplasia
• Reduced learning ability

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• Diagnosis of Fetal Alcohol Syndrome
• Minimal criteria
• Abnormalities in three areas
• Prenatal and/or postnatal growth retardation
• Central nervous system involvement
• Characteristic facial dysmorphology

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When criteria for effect are just disturbances in
CNS function, affected is much higher.
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CNS Dysfunction Infants feeding problems
sleep problems irritable difficult to soothe
abnormal muscle tone Permanent reduced
intelligence behavioral abnormalities (reduced
inhibitory control social difficulties
increased activity) Alcohol is the 1
preventable cause of mental retardation.
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Hormones Readings Chapter 5 and 12
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Cells communicate by chemical signals. Neurotransm
itters - chemicals secreted from a neuron into a
synapse causing changes in postsynaptic
neuron Hormones - chemicals secreted by
specialized cells (neurons secretory cells in
glands and organs) into the bloodstream where
they are carried to other parts of body Endocrine
glands - contain specialized cells that secrete
hormones
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• What is a hormone?
• Chemicals used by the endocrine system to
  influence bodily systems, neuronal activity, and
  behavior
• How do hormones work?
• A lot like neurotransmitters.

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• How do hormones work? A lot like
  neurotransmitters.
• Nervous System uses neurotransmitters to
  directly influence neuronal activity and behavior
• Endocrine System (part is in nervous system)
  uses hormones to directly and indirectly
  influence neuronal activity and behavior, as well
  as other bodily systems.

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Similarities between hormones and
neurotransmitters (nt) 1. Hormones are produced
in endocrine cells and stored there for later
release (nt stored in neurons) 2. Hormone release
must be stimulated by receptor activation (nt
activate receptors) 3. Hormones bind with
specific receptors (nt bind with specific
receptors)
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Similarities between hormones and
neurotransmitters 3. Hormones bind with specific
receptors (nt specific receptors) 4. Hormones
bind with receptors on surface or inside cells
(nt surface membrane) 5. Binding triggers
activities within the cell.
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Similarities between hormones and
neurotransmitters 5. Binding triggers activities
within the cell. 6. Some overlap between cells
and substances that release/serve as hormones and
as neurotransmitters. 7. Drugs/chemicals, diet,
behavior can alter hormone levels and effects.
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Differences between neurotransmitter and hormonal
actions 1. NTs travel over synaptic space to
receiving neuron Hormones travel in blood to
different locations throughout body where
receptors exist. 2. Hormonal communication is
slower (seconds to minutes) than
neurotransmission (milliseconds)
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Differences between neurotransmitter and hormonal
actions 3. Neuronal response to nt is
all-or-none Response to hormones can be graded -
minimal to major effects (with seasonal and daily
rhythms in thresholds). 4. Can more easily
voluntarily control many neural events, but not
hormonal ones (more reflexive).
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Body has many endocrine glands (collections of
secretory cells) In skull Pituitary Pineal
(Hypothalamus) In body Thyroid Thymus
Adrenal Kidneys Pancreas GI Tract
(gastrointestinal) Mammary
glands Gonads - testes ovaries
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