LifeSpan Development of the Brain and Behavior

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Life-Span Development of the Brain and Behavior

• Growth and Brain DevelopmentNeurogenesis to
  Synapse Rearrangement
• Intrinsic v. ExtrinsicMutations and Metabolic
  Disorders

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Growth

• Fertilization, zygote, mitosis
• 46 chromosomes (23 pairs)
• 12 hr zygote divides into two cells
• 3 days, small mass of homogenous cells
• 1 week, 3 cell layers
• Ectoderm
• Neural tube (3 wk) / nervous system)
• Three subdivisions (future forebrain, midbrain,
  hindbrain)
• Mesoderm
• Endoderm

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Development of Nervous System

• Neurogenesis / Proliferation
• Cell migration
• Differentiation
• Synaptogenesis
• Neuronal cell death (apoptosis)
• Synapse rearrangement (refinement)

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Neurogenesis / Cell Proliferation

• Single cell layer of inner neural tube
• Mitosis ventricular zone
• Formation of neurons and glial cells
• Specific brain cells have birth date
• C. elegans cell fate predicted from mitotic
  lineage
• Cell-to-cell interactions
• Neurogenesis after birth, and even into adulthood
• Olfactory neurons replaced throughout life

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Cell Migration

• Radial glial cells guide wires / spokes
• Migration involves cell adhesion molecules (CAMs)
• Adult axon regeneration

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Cell Differentiation

• Gene expression
• Distinctive regional neural appearance
• Two forms of control (of differentiation)
• Intrinsic self-organization
• Cell-autonomous (independent of neighboring
  cells)
• Induction
• Influence of neighboring cells on fate of
  developing cells

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Synaptogenesis

• Growth cones
• Swollen ends of axons dendrites
• Extensions emerge
• Fine outgrowths filopodia
• Sheet-like outgrowths lamellipodia
• Adhere to environment and pull growth cone behind
  it
• Chemical signals
• Chemoattractants
• Chemorepellents

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Cell Death / Apoptosis

• Programmed cell death
• Death genes
• Influx of Ca2
• From outside and inside stores
• Invade mitochondrion
• Diablo gene released
• Block IAPs
• Caspases no longer blocked and destroy proteins
  and DNA of cell
• Bcl-2 proteins can block Diablo (inhibit
  apoptosis)

• Neurotrophic factors
• Nourishment for cells
• Neurotrophin family
• Neurotrophin-1 Nerve growth factor (NGF)
• Neurotrophin-2 (BDNF)
• Neurotrophin-3, -4

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Synapse Rearrangement

• After apoptosis
• Refinement some synapses stay, others lost
• New ones may be added to replace original ones
  lost
• Maintenance / survival
• Promoted by neurotrophins activity at synapse

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Factors that Affect Neural Development

• Intrinsic (genes)
• Chromosomal aberrations
• Single-gene effects / mutations
• Extrinsic
• Nutrients
• Drugs, toxins
• Birth process
• Cell-to-cell interactions (induction, trophic
  factors)
• Neural activity (non-sensory, sensory)

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Genetic Disorders in Humans

• PKU
• Recessive, hereditary disorder
• Genetic disturbance in protein metabolism
• Lack of enzyme to metabolize phenylalanine
• In the absence of metabolism, brain build-up
• Severe mental retardation if phenylalanine not
  reduced
• Down Syndrome
• Chromosomal abnormality
• Extra Chromosome 21
• Greater chance in women over 45 giving birth
• Fragile X Syndrome
• gt200 repeats of CGG nucleotides (of the DNA on
  the long arm of X chromosome)
• Severe facial abnormalities

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Autism and Aspergers Syndrome

• Autism
• Lack of eye contact in infants
• Contributes to reduced facial skills / facial
  recognition (brain activation)
• Impaired language
• Narrow range of interests and activities
• Stereotyped movements
• Mental deficiency may / may not be present
• Reduced corpus callosum, cerebellar regions
• Aspergers Syndrome
• Similar social decline seen in Autism but no loss
  of language

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Brain and Aging

• Memory decline
• Hippocampal shrinkage with age
• Loss in number of cells / synapses
• Can begin as early as 3rd decade of life
• Loss of Betz cell (large neuron of motor cortex)
  beginning at age 50
• Alzheimers Disease
• Senile plaques (degenerating axons and dendrites)
  frontal, temperoparietal, hippocampus and
  limbic sites
• Due to build-up of ?-amyloid (mutation in genes
  that break this down related to AD)
• Neurofibrillary tangles (tau protein) R2 with
  cognitive decline
• Loss of ACh leads to basal forebrain atrophy

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Take Home Message

• Brain growth and development
• Neurogenesis to Synapse rearrangement
• Genes and the environment
• Metabolic, genetic, chromosomal and social
  disorders
• Aging (do it with grace if you can!)