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HMB200H1 (140)
Lecture

HMB200 2014 Lecture 22.pdf

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Department
Human Biology
Course Code
HMB200H1
Professor
John Yeomans

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  Lecture  22:  Developmental  Disorders   -­‐ need  migration  of  cells  by  chemical  gradients  as  they  climb  radial  glial  cells,  then  gene  expression  for  proper   synapses,  proper  growth,  all  the  incoming  cells  from  GABA  and  glutamate  sources  have  to  come  together  to  form   the  layers  and  columns  in  a  very  organized  wa y     Environment  and  Retardation   • retardation:  some  sort  of  cortical  developmental  problem   • development  depends  on  environment,  chemical,  and  toxin  factors,  and  correct  genetic  instructions  (expression  of   the  right  proteins  and  right  developmental  sequences)   • Autism:  GABA  neurons  arrive  late   • Most  common  neurons  (more  GABA  neurons  than   any  other  in  the  brain)   • Spina  bifida  and  folic  acid  (Box  7.4)   • Occurs  when  there  is  a  poor  closure  of  the  spinal   cord   • Early  in  development  (around  25 -­‐26  day)  spinal   cord  closes   • In  spina  bifida,  closure  does  not  close  properly   –   spinal  cord  is  split  à  lots  of  damage  to  the  spinal   th cord  (esp.  20-­‐25  day)   • When  spinal  cord  doesn’t  seal  properly,  it  can  split   into  2  parts  =  poor  motor  control   • Also  associated  with  poor  development  of  th e   cortex  (Small  secondary  retardation  effects)   • Due  to  a  lack  of  folic  acid   • Cerebral  palsy  and  hypoxia  at  birth.     • Difficult  delivery  at  birth   • Umbilical  cord  or  baby’s  breathing  does  occur  =  loss   of  oxygen   • Baby  gets  oxygen  from  umbilical  cord  prenatally,  hav e  to  convert  to  use  lungs  after  birth   • Severe  hypoxia  can  kill  a  lot  of  neurons     • Cells  that  need  oxygen  the  most  at  the  time  of  birth  =  cortical  cells   • This  decrease  in  oxygen  =  death  of  more  cortical  cells  than  another  other   • Cerebral  palsy  is  due  to  environ mental  loss  of  oxygen  usually  at  time  of  delivery   • But  even  after  this  loss  of  oxygen,  the  cortex  CAN  bounce  back   à  can  improve  compared  to  kids  in  genetic   disorders   • Cortex  can  re-­‐organize  itself  through  cortical  plasticity   • Toxins:  lead,  alcohol,  cocaine.   • Lead  poisoning   • Mercury  poisoning   • Heavy  doses  of  alcohol  and  cocaine  will  affect  the  baby   • The  growing  embryo  needs  sufficient   nutrients  and  no  toxins   • Fetal  alcohol  syndrome.   • Found  in  women  who  drink  a  lot  of  alcohol  in  the   and  3  month  of  pregnancy   • Babies  have  series  of  facial  anomalies   • Structural  anomalies  not  associated  with   genetics:  Face  is  flatter,  lips  extend  outward,   frontal  lobe  of  the  cortex  is  smaller   • Even  drink  2-­‐3  glasses  can  decrease  the  intellectual   performance  of  the  baby   nd rd • Critical  period:  2  and  3  month   • See  Mental  Retardation  and  Spines   (Box  2.5)     Chromosomes  and  Genes   • Trisomy  21  (Down’s  Syndrome)   • Added  chromosome  (chromosome  21)       • Extra  chromosome   • Mild  retardation   • Rounder  faces,  cheerful,  changes  in  eye  structure   • Relatively  large  brains   • These  kids  tend  to  get  Alzheimer’s  in  their  40s   • One  of  the  proteins  found  on  chromosome  21  is  the  Amyloid   Precursor  Protein   • By  adding  an  extra  copy  of  this  protein,  accumulation  of   beta-­‐amyloid  is  higher  than  normal   • Extra  amyloid  can  be  cleared  throughou t  early  development   (with  good  circulation  in  brain),  but  as  they  get  older,   amyloid  accumulates  because  of  the  extra  production  of  the   amyloid  precursor  protein   • Amyloid  poisoning  of  the  cortex,  loss  of  memory  function,  loss  of  intellectual  function  (start s  in   late  30s  to  early  50s)   • 2  proteins  that  accumulate  in  Alzheimer’s:   1) beta-­‐amyloid  –  one  of  the  breakdown  products  of  the  amyloid  precursor  protein   -­‐  extracellular  accumulation  induces  formation  of  amyloid  plaques  =  synaptic  and   cortical  damage   2) tau  protein  –  produces  neural  fibrillary  tangles  inside  brain  neurons   -­‐ these  two  together  leads  to  the  most  expensive  neurological  disorder   -­‐ chromosome  21  is  the  shortest  among  all  the  chromosomes,  an  extra  chromosome  21  =  not  a  big  addition  of   proteins   -­‐ kids  with  trisomy  21  down  syndrome  doesn’t  really  have  bad  retardation  or  sever  symptoms   à  only  because   chromosome  21  is  shortest  of  all   -­‐ trisomy  on  longer  chromosomes  =  more  severe   -­‐ trisomy  15  and  13  =  lethal  in  babies   -­‐ the  more  excess  proteins,  the  more  severe  the  defici ts  and  retardation   • Fragile  X      (CGG  repeats  on  Ch  X)     • Due  to  sequence  problems  on  the  X  chromosome   • Produce  a  series  of  CCG  repeats  (tri -­‐nucleotide  repeat)  on  chromosome  X27   • Repeated  amino  acid  =  protein  doesn’t  work  properly   • Results  in  a  fragile  chromosome  à  chromosome  breaks  at  the  tip  of  the  chromosome   • Long  end:  Q  arm  of  the  chromosome   • XQ27:  where  the  break  occurs   • Symptoms:  autistic  like   • Genetic  break  on  X  chromosome  that  leads  to  autism  in  boys   • Males  only  have  1  X  chromosome   à  males  more  vulnerable     • Autism  (many  genes)  Unsociable  –  genetic  and  environmental  cause   • Fragile  X  –  quite  severe  in  males   • Don’t  like  to  hug  others,  good  at  technical  things   • No  symptoms  at  time  of  birth,  develops  in  the  first  few  months  after  birth,  gets  worst  over  the  first  few   years   • Developmental  onset  =  postnatal  change  rather  than  prenatal  change  (even  in  fragile  X)   • Oxytocin   • 4X  more  males  in  autism  –  males  have  lower  levels  of  oxytocin   • males  more  susceptible,  less  oxytocin  to  protect  them   • high  oxytocin  =  stimulation  of  cuddling,  s ocial  interest,  etc.  –  females  less  vulnerable   • released  by  mother  in  2  conditions:  during  contraction  to  facilitate  birth  (high  levels  of  oxytocin   stimulates  delivery  of  the  baby),  and  breastfeeding  (tactile  reflex  results  in  oxytocin  production  in   the
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