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Anatomic Gene Expression Mapping Natalia Jiménez Lozano  (natalia@cnb.csic.es)
Guidelines
… Rho Sox2 Aspn Pax6 … Wonder  which genes  are expressed (e.g. in the retina)
… during the  development
… during the  development … Col1a1 Cryaa Ebf1 Ephb1 Opn3 Opn4  Pax6 Pou4f1 Pou4f2 Rgr Rho Rrh Serpinh1 …
Pax6 Wonder  where genes are expressed (e.g. Pax6)
… during the  development
… during the  development Pax6
 
This is a  mess!
GXD EMAGE GENSAT In situ hybridization All kind of techniques except microarrays bacterial artificial chromosomes (BACs)   BioGPS Microarrays
It is not mandatory to do such  effort!
If she can  why  not me?
 
Gene expression is defined by which  (genes)  and where  (anatomic structures)
Ontology   alignment
 
 
What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is? What is aGEM? What is aGEM? What is? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? ? ? ? ? ? What is aGEM? What is aGEM? What is aGEM?
 
… during the  development … Col1a1 Cryaa Ebf1 Ephb1 Opn3 Opn4 Pax6 Pou4f1 Pou4f2 Rgr Rho Rrh Serpinh1 …
Pax6  expresses  strongly  in  retina  during  TS22 …
…  and  co-expresses  with Tcf7l2
 
 
… during the  development Pax6
Pax6  expresses widely  during the development
Pax6 has a similar expression pattern in  CNS  and  retina
 
 
 
A  real  case
Neurodegenerative  diseases
 
 
 
 
 
 
 
 
 
Parkinson’s  disease
Parkinson’s  disease pancreas metencephalon cerebellum  midbrain hippocampus diencephalon basal ganglia amygdala hypothalamus nervous system central nervous system forebrain brain telencephalon cerebral cortex cerebral cortex region myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex hippocampus region olfactory cortex pons pallidum thalamus septal cortex lateral septal cortex Cox6b1 Atp5g3 Cycs Ndufa9 Ndufb7 Ndvfs7 Sdhb Uqcr Uqcrb Ndufb10 Atp5o Uqcrfs1 Cox5a Atp5c1 Cox5b Ndufa6 Cyc1 Atp5b Ndufs3 Ndufv2 Atp5h Atp5a1 Udac1 Ndufv1 Slc25a4 Ube2l3 Atp5d Nudfa5 Sdha Uqcrc1 Ndufb9 Cox7a2 Uchl1 Ndufs2 Ndufa10 Cox4i1
pancreas metencephalon cerebellum  midbrain hippocampus diencephalon basal ganglia amygdala hypothalamus nervous system central nervous system forebrain brain telencephalon cerebral cortex cerebral cortex region myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex hippocampus region olfactory cortex pons pallidum thalamus septal cortex lateral septal cortex Parkinson’s  disease Cox6b1 Atp5g3 Cycs Ndufa9 Ndufb7 Ndvfs7 Sdhb Uqcr Uqcrb Ndufb10 Atp5o Uqcrfs1 Cox5a Atp5c1 Cox5b Ndufa6 Cyc1 Atp5b Ndufs3 Ndufv2 Atp5h Atp5a1 Udac1 Ndufv1 Slc25a4 Ube2l3 Atp5d Nudfa5 Sdha Uqcrc1 Ndufb9 Cox7a2 Uchl1 Ndufs2 Ndufa10 Cox4i1
pancreas metencephalon cerebellum  midbrain hippocampus diencephalon basal ganglia amygdala hypothalamus nervous system central nervous system forebrain brain telencephalon cerebral cortex cerebral cortex region myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex hippocampus region olfactory cortex pons pallidum thalamus septal cortex lateral septal cortex
 
Alzheimer’s  disease pancreas nervous system central nervous system brain forebrain telencephalon cerebral cortex cerebral cortex region basal ganglia amygdala diencephalon hypothalamus hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain pons hippocampal formation tetrohippocampal cortex hipocampus region olfactory cortex thalamus septal cortex lateral septal complex pallidum Cacna1c Cdk5 Cox4i1 Gsk3b Cox7a2 Ndufb9 Uqcrc1 Apoe Ndufv1 Atp5h Ndufv2 Ndufs3 Cyc1 Calm2 Atp5b Calm1 Ndufa6 Cox5b Atp5c1 Cox5a Atp5a1 Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1
pancreas nervous system central nervous system brain forebrain telencephalon cerebral cortex cerebral cortex region basal ganglia amygdala diencephalon hypothalamus hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain pons hippocampal formation tetrohippocampal cortex hipocampus region olfactory cortex thalamus septal cortex lateral septal complex pallidum Cacna1c Cdk5 Cox4i1 Gsk3b Cox7a2 Ndufb9 Uqcrc1 Apoe Ndufv1 Atp5h Ndufv2 Ndufs3 Cyc1 Calm2 Atp5b Calm1 Ndufa6 Cox5b Atp5c1 Cox5a Atp5a1 Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1 Alzheimer’s  disease
pancreas nervous system central nervous system brain forebrain telencephalon cerebral cortex cerebral cortex region basal ganglia amygdala diencephalon hypothalamus hippocampus Midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain pons hippocampal formation tetrohippocampal cortex hipocampus region olfactory cortex thalamus septal cortex lateral septal complex pallidum
 
Non redundant  set of genes=344 Amylotrophic Lateral Sclerosis Parkinson disease Alzheimer disease Huntington disease
Four  neurodegenerative  diseases pancreas nervous system central nervous system brain telencephalon forebrain cerebral cortex cerebral cortex region diencephalon hypothalamus basal ganglia amygdala hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex olfactory complex hippocampus region septal cortex lateral septal complex pallidum thalamus pons Gsk3b Cox7a2 Uchl1 Apoe Slc25a4 Ap2m1 Dctn2 Ap2s1 Ndufv1 Vdac1 Atp5a1 Dctn1 Atp5h Clta Ndufv2 Ndufs3 Cyc1 Cltc Calm2 Atp5b Calm1 Ube2l3 Ndufb9 Uqcrc1 Rac1 Ndufa6 Cox5b Atp5c1 Cox5a Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Rab5a Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1
pancreas nervous system central nervous system brain telencephalon forebrain cerebral cortex cerebral cortex region diencephalon hypothalamus basal ganglia amygdala hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex olfactory complex hippocampus region septal cortex lateral septal complex pallidum thalamus pons Four  neurodegenerative  diseases Gsk3b Cox7a2 Uchl1 Apoe Slc25a4 Ap2m1 Dctn2 Ap2s1 Ndufv1 Vdac1 Atp5a1 Dctn1 Atp5h Clta Ndufv2 Ndufs3 Cyc1 Cltc Calm2 Atp5b Calm1 Ube2l3 Ndufb9 Uqcrc1 Rac1 Ndufa6 Cox5b Atp5c1 Cox5a Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Rab5a Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1
pancreas nervous system central nervous system brain telencephalon forebrain cerebral cortex cerebral cortex region diencephalon hypothalamus basal ganglia amygdala hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex olfactory complex hippocampus region septal cortex lateral septal complex pallidum thalamus pons
 
 
“ Approximately  20%  of neurodegenerative disorders are associated with diabetes mellitus ” -Michael Ristow, 2004
-Michael Ristow, 2004 Typical Woodhouse-Sakati syndrome Typical Wolfram syndrome/DIDMOAD Typical Werner syndrome Frequent Turner syndrome Rare Spinocerebellar ataxia 6 Frequent Prader-Willi syndrome Mainly Impaired glucose intolerance Parkinson disease Rare Norrie disease Frequent Narcolepsy Frequent Huntington disease Typical Herrmann syndrome Frequent Friedereich ataxia Typical Feigenbaum syndrome Frequent Down syndrome Frequent Cerebellar ataxia, deafness, and narcolepsy Frequent Bardet-biedl syndrome Recent evidence Alzheimer disease Extreme insulin resistance Ataxia-telangiectasia Typical Alstöm syndrome Typical Aceruloplasminemia Diabetes Mellitus Disorder
-Michael Ristow, 2004 Typical Woodhouse-Sakati syndrome Typical Wolfram syndrome/DIDMOAD Typical Werner syndrome Frequent Turner syndrome Rare Spinocerebellar ataxia 6 Frequent Prader-Willi syndrome Mainly Impaired glucose intolerance Parkinson disease Rare Norrie disease Frequent Narcolepsy Frequent Huntington disease Typical Herrmann syndrome Frequent Friedereich ataxia Typical Feigenbaum syndrome Frequent Down syndrome Frequent Cerebellar ataxia, deafness, and narcolepsy Frequent Bardet-biedl syndrome Recent evidence Alzheimer disease Extreme insulin resistance Ataxia-telangiectasia Typical Alstöm syndrome Typical Aceruloplasminemia Diabetes Mellitus Disorder
Hallmarks  in Alzheimer disease
Amyloid-beta plaque
“ Amyloid  protein deposits are commonly observed in pancreatic  islets of diabetic patients ” -Opie EL, 1901
“ Deposits observed in pancreatic islets of diabetic patients consists on islet  amyloid polypeptide (IAPP) ”
“ Beta precursor protein and IAPP have  90% structural similarity ”
“ Alzheimer  disease seems to predispose for insulin resistance, insulin hypersecretion and  type 2 diabetes  mellitus ” -Razay G, 1994
“ Individuals suffering from  type 2 diabetes  show an increased prevalence of  dementia ” -Ott A, 1999
 
“ Impaired glucose tolerance is frequently observed in Parkinson disease and affects  up to   80%  of patients. [...] therapy with levodopa seems to exacerbate glucose intolerance ”
“ PD is characterized histologicaly by a  loss   of dopaminergic neurons  in the substantia nigra where insulin receptors are densely represented”
“ Insulin increases the expression of dopamine transporter 1 in substantia nigra and  regulates  brain dopamine concentrations ”
 
Non Huntington Huntington “ A typical  atrophy  of the caudate nucleus is observed radiographically …
… this affection is preceded by impaired glucose metabolism in this nucleus ”
“ Huntington patients develop diabetes mellitus about seven times more often than matched healthy control individuals” -Podolsky S,   1972
“   Examination has revealed low insulin gene expression in the pancreas of HD transgenic animals “ - Craft S, 2004
 
In a nutshell
Integrative
Easy to use
Useful in Biomedical studies
http://agem.cnb.csic.es [email_address]
The  team
aGEM integrative   easy to use useful in biomedical studies
 
 
Huntington  disease
Huntington  disease
Huntington  disease
 
Amylotrophic lateral sclerosis
Amylotrophic lateral sclerosis
Amylotrophic lateral sclerosis
“ HD is attributed to the  CAG repeat  in the huntingtin gene ”
“ Toxicity arises from the cleavage and accumulation of amino-terminal fragments containing an expanded  polyglutamine region , which might be due to an increased resistance against proteolytic cleavage of mutant huntingtin ”   -Dyer RB, 2001

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anatomic Gene Expression Mapping

  • 1. Anatomic Gene Expression Mapping Natalia Jiménez Lozano (natalia@cnb.csic.es)
  • 3. … Rho Sox2 Aspn Pax6 … Wonder which genes are expressed (e.g. in the retina)
  • 4. … during the development
  • 5. … during the development … Col1a1 Cryaa Ebf1 Ephb1 Opn3 Opn4 Pax6 Pou4f1 Pou4f2 Rgr Rho Rrh Serpinh1 …
  • 6. Pax6 Wonder where genes are expressed (e.g. Pax6)
  • 7. … during the development
  • 8. … during the development Pax6
  • 9.  
  • 10. This is a mess!
  • 11. GXD EMAGE GENSAT In situ hybridization All kind of techniques except microarrays bacterial artificial chromosomes (BACs) BioGPS Microarrays
  • 12. It is not mandatory to do such effort!
  • 13. If she can why not me?
  • 14.  
  • 15. Gene expression is defined by which (genes) and where (anatomic structures)
  • 16. Ontology alignment
  • 17.  
  • 18.  
  • 19. What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is? What is aGEM? What is aGEM? What is? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? What is aGEM? ? ? ? ? ? What is aGEM? What is aGEM? What is aGEM?
  • 20.  
  • 21. … during the development … Col1a1 Cryaa Ebf1 Ephb1 Opn3 Opn4 Pax6 Pou4f1 Pou4f2 Rgr Rho Rrh Serpinh1 …
  • 22. Pax6 expresses strongly in retina during TS22 …
  • 23. … and co-expresses with Tcf7l2
  • 24.  
  • 25.  
  • 26. … during the development Pax6
  • 27. Pax6 expresses widely during the development
  • 28. Pax6 has a similar expression pattern in CNS and retina
  • 29.  
  • 30.  
  • 31.  
  • 32. A real case
  • 34.  
  • 35.  
  • 36.  
  • 37.  
  • 38.  
  • 39.  
  • 40.  
  • 41.  
  • 42.  
  • 44. Parkinson’s disease pancreas metencephalon cerebellum midbrain hippocampus diencephalon basal ganglia amygdala hypothalamus nervous system central nervous system forebrain brain telencephalon cerebral cortex cerebral cortex region myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex hippocampus region olfactory cortex pons pallidum thalamus septal cortex lateral septal cortex Cox6b1 Atp5g3 Cycs Ndufa9 Ndufb7 Ndvfs7 Sdhb Uqcr Uqcrb Ndufb10 Atp5o Uqcrfs1 Cox5a Atp5c1 Cox5b Ndufa6 Cyc1 Atp5b Ndufs3 Ndufv2 Atp5h Atp5a1 Udac1 Ndufv1 Slc25a4 Ube2l3 Atp5d Nudfa5 Sdha Uqcrc1 Ndufb9 Cox7a2 Uchl1 Ndufs2 Ndufa10 Cox4i1
  • 45. pancreas metencephalon cerebellum midbrain hippocampus diencephalon basal ganglia amygdala hypothalamus nervous system central nervous system forebrain brain telencephalon cerebral cortex cerebral cortex region myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex hippocampus region olfactory cortex pons pallidum thalamus septal cortex lateral septal cortex Parkinson’s disease Cox6b1 Atp5g3 Cycs Ndufa9 Ndufb7 Ndvfs7 Sdhb Uqcr Uqcrb Ndufb10 Atp5o Uqcrfs1 Cox5a Atp5c1 Cox5b Ndufa6 Cyc1 Atp5b Ndufs3 Ndufv2 Atp5h Atp5a1 Udac1 Ndufv1 Slc25a4 Ube2l3 Atp5d Nudfa5 Sdha Uqcrc1 Ndufb9 Cox7a2 Uchl1 Ndufs2 Ndufa10 Cox4i1
  • 46. pancreas metencephalon cerebellum midbrain hippocampus diencephalon basal ganglia amygdala hypothalamus nervous system central nervous system forebrain brain telencephalon cerebral cortex cerebral cortex region myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex hippocampus region olfactory cortex pons pallidum thalamus septal cortex lateral septal cortex
  • 47.  
  • 48. Alzheimer’s disease pancreas nervous system central nervous system brain forebrain telencephalon cerebral cortex cerebral cortex region basal ganglia amygdala diencephalon hypothalamus hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain pons hippocampal formation tetrohippocampal cortex hipocampus region olfactory cortex thalamus septal cortex lateral septal complex pallidum Cacna1c Cdk5 Cox4i1 Gsk3b Cox7a2 Ndufb9 Uqcrc1 Apoe Ndufv1 Atp5h Ndufv2 Ndufs3 Cyc1 Calm2 Atp5b Calm1 Ndufa6 Cox5b Atp5c1 Cox5a Atp5a1 Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1
  • 49. pancreas nervous system central nervous system brain forebrain telencephalon cerebral cortex cerebral cortex region basal ganglia amygdala diencephalon hypothalamus hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain pons hippocampal formation tetrohippocampal cortex hipocampus region olfactory cortex thalamus septal cortex lateral septal complex pallidum Cacna1c Cdk5 Cox4i1 Gsk3b Cox7a2 Ndufb9 Uqcrc1 Apoe Ndufv1 Atp5h Ndufv2 Ndufs3 Cyc1 Calm2 Atp5b Calm1 Ndufa6 Cox5b Atp5c1 Cox5a Atp5a1 Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1 Alzheimer’s disease
  • 50. pancreas nervous system central nervous system brain forebrain telencephalon cerebral cortex cerebral cortex region basal ganglia amygdala diencephalon hypothalamus hippocampus Midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain pons hippocampal formation tetrohippocampal cortex hipocampus region olfactory cortex thalamus septal cortex lateral septal complex pallidum
  • 51.  
  • 52. Non redundant set of genes=344 Amylotrophic Lateral Sclerosis Parkinson disease Alzheimer disease Huntington disease
  • 53. Four neurodegenerative diseases pancreas nervous system central nervous system brain telencephalon forebrain cerebral cortex cerebral cortex region diencephalon hypothalamus basal ganglia amygdala hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex olfactory complex hippocampus region septal cortex lateral septal complex pallidum thalamus pons Gsk3b Cox7a2 Uchl1 Apoe Slc25a4 Ap2m1 Dctn2 Ap2s1 Ndufv1 Vdac1 Atp5a1 Dctn1 Atp5h Clta Ndufv2 Ndufs3 Cyc1 Cltc Calm2 Atp5b Calm1 Ube2l3 Ndufb9 Uqcrc1 Rac1 Ndufa6 Cox5b Atp5c1 Cox5a Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Rab5a Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1
  • 54. pancreas nervous system central nervous system brain telencephalon forebrain cerebral cortex cerebral cortex region diencephalon hypothalamus basal ganglia amygdala hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex olfactory complex hippocampus region septal cortex lateral septal complex pallidum thalamus pons Four neurodegenerative diseases Gsk3b Cox7a2 Uchl1 Apoe Slc25a4 Ap2m1 Dctn2 Ap2s1 Ndufv1 Vdac1 Atp5a1 Dctn1 Atp5h Clta Ndufv2 Ndufs3 Cyc1 Cltc Calm2 Atp5b Calm1 Ube2l3 Ndufb9 Uqcrc1 Rac1 Ndufa6 Cox5b Atp5c1 Cox5a Uqcrfs1 Atp5o Ndufb10 Uqcrb Uqcr Sdhb Rab5a Ndufs7 Ndufb7 Ndufa9 Cycs Atp5g3 Cox6b1
  • 55. pancreas nervous system central nervous system brain telencephalon forebrain cerebral cortex cerebral cortex region diencephalon hypothalamus basal ganglia amygdala hippocampus midbrain metencephalon cerebellum myencephalon medulla oblongata hindbrain hippocampal formation retrohippocampal cortex olfactory complex hippocampus region septal cortex lateral septal complex pallidum thalamus pons
  • 56.  
  • 57.  
  • 58. “ Approximately 20% of neurodegenerative disorders are associated with diabetes mellitus ” -Michael Ristow, 2004
  • 59. -Michael Ristow, 2004 Typical Woodhouse-Sakati syndrome Typical Wolfram syndrome/DIDMOAD Typical Werner syndrome Frequent Turner syndrome Rare Spinocerebellar ataxia 6 Frequent Prader-Willi syndrome Mainly Impaired glucose intolerance Parkinson disease Rare Norrie disease Frequent Narcolepsy Frequent Huntington disease Typical Herrmann syndrome Frequent Friedereich ataxia Typical Feigenbaum syndrome Frequent Down syndrome Frequent Cerebellar ataxia, deafness, and narcolepsy Frequent Bardet-biedl syndrome Recent evidence Alzheimer disease Extreme insulin resistance Ataxia-telangiectasia Typical Alstöm syndrome Typical Aceruloplasminemia Diabetes Mellitus Disorder
  • 60. -Michael Ristow, 2004 Typical Woodhouse-Sakati syndrome Typical Wolfram syndrome/DIDMOAD Typical Werner syndrome Frequent Turner syndrome Rare Spinocerebellar ataxia 6 Frequent Prader-Willi syndrome Mainly Impaired glucose intolerance Parkinson disease Rare Norrie disease Frequent Narcolepsy Frequent Huntington disease Typical Herrmann syndrome Frequent Friedereich ataxia Typical Feigenbaum syndrome Frequent Down syndrome Frequent Cerebellar ataxia, deafness, and narcolepsy Frequent Bardet-biedl syndrome Recent evidence Alzheimer disease Extreme insulin resistance Ataxia-telangiectasia Typical Alstöm syndrome Typical Aceruloplasminemia Diabetes Mellitus Disorder
  • 61. Hallmarks in Alzheimer disease
  • 63. “ Amyloid protein deposits are commonly observed in pancreatic islets of diabetic patients ” -Opie EL, 1901
  • 64. “ Deposits observed in pancreatic islets of diabetic patients consists on islet amyloid polypeptide (IAPP) ”
  • 65. “ Beta precursor protein and IAPP have 90% structural similarity ”
  • 66. “ Alzheimer disease seems to predispose for insulin resistance, insulin hypersecretion and type 2 diabetes mellitus ” -Razay G, 1994
  • 67. “ Individuals suffering from type 2 diabetes show an increased prevalence of dementia ” -Ott A, 1999
  • 68.  
  • 69. “ Impaired glucose tolerance is frequently observed in Parkinson disease and affects up to 80% of patients. [...] therapy with levodopa seems to exacerbate glucose intolerance ”
  • 70. “ PD is characterized histologicaly by a loss of dopaminergic neurons in the substantia nigra where insulin receptors are densely represented”
  • 71. “ Insulin increases the expression of dopamine transporter 1 in substantia nigra and regulates brain dopamine concentrations ”
  • 72.  
  • 73. Non Huntington Huntington “ A typical atrophy of the caudate nucleus is observed radiographically …
  • 74. … this affection is preceded by impaired glucose metabolism in this nucleus ”
  • 75. “ Huntington patients develop diabetes mellitus about seven times more often than matched healthy control individuals” -Podolsky S, 1972
  • 76. Examination has revealed low insulin gene expression in the pancreas of HD transgenic animals “ - Craft S, 2004
  • 77.  
  • 84. aGEM integrative easy to use useful in biomedical studies
  • 85.  
  • 86.  
  • 90.  
  • 94. “ HD is attributed to the CAG repeat in the huntingtin gene ”
  • 95. “ Toxicity arises from the cleavage and accumulation of amino-terminal fragments containing an expanded polyglutamine region , which might be due to an increased resistance against proteolytic cleavage of mutant huntingtin ” -Dyer RB, 2001