Lecture 7 Radiation continued

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Lecture 7 Radiation continued Sept 29, 2005 I.
Radiation Measurement Units A. RAD (radiation
absorbed dose) - measures absorbed dose
- the amount of energy actually absorbed in
some material - used for any type of
radiation and any material - does not
describe the biological effects of the different
radiations 1 rad the absorption of 100 ergs per
gram of material B. Gray - another unit used to
measure absorbed dose - also used for any type
of radiation and any material - Absorbed dose is
often expressed in terms of hundredths of a gray,
or centigrays. 1 gray 100 rads
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Radiation Measurement Units C. REM (roentgen
equivalent in man) -US system - used to
derive equivalent dose - relates the
absorbed dose in human tissue to the amount of
biological
damage - To determine equivalent
dose (rem), you multiply absorbed dose (rad) by a
quality factor (Q) that is
unique to the type of radiation - mrem
sometimes used thousandths of a rem
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• II. Research on Health Effects of Radiation on
  Neurological and Cognitive Processes
• A. General Design (Otake and Schull, 1998)
• done primarily on survivors of atomic bombs
  dropped in Japan in WWII Nagasaki and Hiroshima
• lowest level harmful effects were seen following
  exposure during prenatal development
• 1565 kids born within 10 months of bombings kids
  were divided into groups based on the distance
  they lived from the center of the bombings
• 1. those proximally exposed (within 2000 m of
  the center)
• 2. those distally exposed (30004999 m)
• 3. and those unexposed (gt10,000 m)
• each group matched based on childs sex and
  prenatal stage at time of exposure
• compared exposure during prenatal weeks 0-7
  8-15 16-25 26 to end
• calculated doses in centiGrays cGy
• 1 cGy0.01Gy
• examined multiple endpoints

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II. Research on Health Effects of Radiation on
Neurological and Cognitive Processes B.
Results 1. Mental Retardation defined by
clinical observation or testing severe end
of MR spectrum Exposure during weeks 0-7 mainly
led to miscarriage. MR increased following
exposures in 8-25 week period. Brain appeared
resistant MR from radiation exposures during
weeks 26-40 Harmful dose levels that caused
MR weeks 815 postconception gt 0.55 Gy weeks
1625 postconception gt 0.87 Gy If exposed to 1
Gy between weeks 8-15 (the most sensitive
period), risks for MR was 44.
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II. Research on Health Effects of Radiation on
Neurological and Cognitive Processes B.
Results 2. IQ 95 of the sample were given IQ
tests at 10-11 years of age As far MR, no
dose-related decreases in IQ if exposure occurred
prior during 0-7 weeks or after 25 weeks. As
far MR, rates worse during 8-15 weeks than during
16-25. Marked IQ decreases when dose above 0.5
Gy. 8-15 weeks When MR in sample, IQ reduced
by 25 points/Gy exposure When MR removed, IQ
reduced by 21 points/Gy exposure 16-25 weeks MR
in, IQ reduced by 21 points MR out, IQ reduced
by 13 points Data from Chernobyl incident are
generally similar.
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II. Research on Health Effects of Radiation on
Neurological and Cognitive Processes C. Actions
of Radiation on Developing Nervous System 2
arguments - direct action on developing
cells - action on thyroid followed by
consequences to brain development D. Brain
development
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Human Pregnancy -38 weeks long - 40 if you count
from last menstrual period as radiation article
did
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Stages of pregnancy (38 weeks long) 1.
Preimplantation period - days 0-14 2. Embryonic
period - days 15-60 3. Fetal period - days 61
until birth Growth and differentiation of organ
systems - to completion for all organs except
brain
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From Neuroscience for Kids webpage
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• Processes during early development
• Proliferation - replication of cells birth of
  cells
• Migration - movement of cells to their destined
  location
• Differentiation - specialization of cells into
  their destined type phenotype specified

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• Processes during neural development
• Proliferation
• Migration
• Differentiation
• Elaboration - formation of dendrites and axons
• Synaptogenesis - formation of connections

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• Processes during neural development
• Proliferation
• Migration
• Differentiation
• Elaboration
• Synaptogenesis
• Gliogenesis - formation of glial cells
• (Myelination - formation of myelin)

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• Processes during neural development
• Elaboration
• Synaptogenesis
• Gliogenesis
• Apoptosis - programmed cell death
• removes about half of all neurons created
• occurs prior to birth, during infancy, and
  again in adolescence

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Principles of Neural Development 1. Proceeds from
hindbrain to forebrain (caudal to rostral
gradient) 2. Degree and timing of neurogenesis
varies across brain areas 3. Gliogenesis of
Radial glia (tracks) and microglia (clean up
debris) form in parallel with neurogenesis
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Principles of Neural Development 3. Radial glia
(tracks) and microglia (clean up debris) form in
parallel with neurogenesis 4. Other glial cells
(myelin) develop after neuronal differentiation
and elaboration 5. 6 cortical layers- layer I is
outmost, layer VI is deepest. VI-I form inside
out - deeper layers form first.
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• Nervous System - preimplantation period - not
  present in humans
• Nervous System- embryonic period
• Formation of neural plate - day 14
• Formation of neural groove and folds- day 18
• Fusion of folds begins - day 22
• Neural tube closes - day 26
• Tube forms the spinal cord and other cells
  migrate to form the early brain

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• Nervous system - Embryonic period
• Neural tube closes - day 26
• Tube forms the spinal cord and other cells
  migrate to form the early brain
• Hindbrain, midbrain, then forebrain develop
  all present by day 28
• Then, 3 parts grow into 5.
• continued proliferation and migration of
  neurons differentiation begins for some
• proliferation and differentiation of some glia

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Nervous system End of Embryonic period 7 weeks
after conception 5 divisions of adult brain are
present in rudimentary form. 1. Forebrain A.
Telencephalon B. Diencephalon 2. Midbrain
A. Mesencephalon 3. Hindbrain A.
Metencephalon B. Myelencephalon
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• Development in the Fetal Period
• formation of cortex
• continued proliferation and migration (before
  and after birth)
• elaboration and differentiation
• synaptogenesis and myelination
• apoptosis in some areas
• birth occurs - most processes continue

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• Human Postnatal Brain Development
• Infancy
• overproduction of neurons and synapses beginning
  in fetal period and continuing to about 18 months
  of age
• apoptosis and pruning of synapses continues to
  about 2 years of age
• Adolescent Period another wave of development

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• Postnatal brain development
• Differentiation and synaptogenesis and apoptosis
  continue
• prefrontal cortex, cerebellum, and hippocampus
  complete development postnatally
• certain fiber tracts serving the prefrontal
  cortex are not completely formed until after
  adolescence (reductions in inputs due to
  apoptotic pruning)

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• Adolescent Brain Development
• overproduction of neurons and their axons
  peaking at 11 years in girls 12 years in boys
• pruning through age 20 with final stages
  occurring in highest brain areas prefrontal
  cortex and lateral temporal lobes
• Overproduction then pruning of receptors for
  several systems (DA, 5HT, GABA/BZD, ACH, GLU)
• major decline in excitatory stimulation of
  cortex (from diffuse to focal)

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From Gogtay et al, 2004. 13 children were scanned
at 2 year intervals from 4-20 years. Blue
represents a decline in gray matter density
(neuronal density).