A Comprehensive Overview of Central Nervous System

Cells of the Central Nervous System 

They are classified into two different types: 

1. Glial cells: These are further divided into:
   • Astrocytes 
   • Oligodendrocytes 
   • Ependymal cells 
2. Macrophages 

Glial Cells 

1. Astrocytes 

• These are star-shaped cells. 
• IHC stain: glial fibrillary acidic protein marker.

Functions

• Formation of the Blood-Brain Barrier (BBB). 
• Involved in the repair mechanism.

B. Oligodendrocytes

• Formation of the myelin sheath (helps in fast conduction of impulses) in the CNS.
• Special stain for myelin: Luxol fast blue.

C. Ependymal cells

• Present in ventricles of the brain. 
• Formation of cerebrospinal fluid (CSF).

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Macrophages

• Other name: Microglia (in brain)

Modified Macrophages

Response to Injury

• Astrocytes become giant and pink (gemistocytes). 
• Alzheimer (no memory loss) astrocytes seen in Type 1 progressive multifocal leukoencephalopathy. 
• Alzheimer's (no memory loss) is found in Type 2 hepatic encephalopathy (damage by ammonia). 
• Rosenthal fibers:
  • Not specific 
  • Made of ubiquitin, alpha-beta crystallin, heat shock protein, and GFAP. 
  • They are seen in:
    • Juvenile pilocytic astrocytomas 
    • Alexander's disease 
    • Gliosis

Also read: Important Pathology Questions on Cell Injury – MCQs & Key

Prion Diseases

• Other Name: TSE (Transmissible Spongiform Encephalopathy). 
• Route of transmission: Iatrogenic route 
• Spongiform: Vacuolization (inside the cell)

Pathogenesis

• Normal prion proteins are found in nerve cells (alpha-helical)

 ↓Misfolding 

Sc · Formation of PrP (beta-pleated configuration) 

↓ 

• Mainly occurs due to the polymorphism at codon 129

Diseases

• Creutzfeldt-Jakob disease 
• Fatal familial insomnia (FFI) 
• Kuru disease-PAS & Congo red positive 
• Scrapie disease (sheep) 
• Bovine spongiform encephalopathy (animal association) 
• Mink transmissible encephalopathy (animal association)
• All these show spongiform changes except FFI.

Codons

• Prion disease: caused by the mutation of codon 129. 
• Aflatoxin (p53 gene) due to the mutation of codon 249. 
• BRAF V600 E 
• JAK2 V617F: Polycythemia

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Neuro-degenerative Disorders

1. Alzheimer's Disease

• Element of dementia. 
• Seen in old age people (>70 years). 

• The Amyloid Precursor Protein (APP) gene is present in chromosome 21. 
• APP gene has two pathways:
  • Amyloidogenic pathway
    • Has beta-secretase activity (A β 40 and Aβ 42) 
    • Gamma-secretase enzyme activity 
  • Non-amyloidogenic pathway
    • Has alpha-secretase activity 
    • Gamma-secretase enzyme activity

A β42-key initiator of Alzheimer's disease 

↓ 

βplaque

 ↓ 

Meyernet Nucleus 

↓ Reduced acetylcholine levels 

↓ 

Dementia

Genetics of Alzheimer's Disease 

• APP gene:
  • Trisomy 21: more APP leads to presenile Alzheimer's disease. 
• Presenilin 1 gene 
  • Present in chromosome 14
  • Increases the levels of gamma-secretase activity
• Presenilin 2 gene 
  • Present in chromosome 1 
  • Activity of gamma-secretase enzyme is increased 
• ApoE4 gene 
  • Present in chromosome 19 
  • Early onset of Alzheimer's disease

Pathology of Alzheimer's Disease

• Neuritic plaques:
  • Core of Amyloid (Aβ 42) in the center.
  • Damaged nerves are accumulated (dystrophic nerve fibers) 
  • Bielschowsky stain is used to observe the neuritic plaques. 

• Neurofibrillary Tangles
  • Flame cells 
  • Made of hyperphosphorylated Tau protein

• Cerebral amyloid angiopathy: 
  • Blood vessels present in the brain are affected due to Aβ 40. 
• Granula-vascular degeneration: 
  • Degeneration of cells 
• Hirano bodies: 
  • Needle-shaped body 
  • Made of actin 

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ii.Parkinson's Disease 

• Decrease in dopaminergic neurons. 
• Decrease in melanin (pale substantia nigra).
• Symptoms: Tremors, rigidity, slow movement (bradykinesia). 

Genetics of Parkinson's Disease

Mutations : 

• Alpha-synuclein
  • Gain-of-function 
  • Forms Lewy bodies 
• LRRK2 
• PINK
• Parkin

iii. Huntington's disease/Huntington's chorea: 

• Purposeless jerky movements 
• CAG repeats on the exon of chromosome 4 
• Proteins: Increase in Polyglutamate, Huntintin, and Ubiquitin proteins 

↓ 

Accumulates in the caudate nucleus 

↓ 

Chorea ↓ Purposeless jerky movements

iv. Amyotrophic Lateral Sclerosis 

• Involves both upper motor neuron and lower motor neuron. 
• Presence of bunina bodies. 
• SOD 1 gene mutations.

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Overview: Most Expected Questions

Proteins & Diseases

FTLD-TDP: Expansion of a hexanucleotide repeat of C9orf72

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Important questions

Q. How is myelin sheath formed in PNS? 

Ans: Schwann cells

Q. What are the brain changes in HIV-positive individuals? 

Ans: Microglial nodules 

Q. In which condition rod-shaped cells are found? 

Ans: Neurosyphilis (Tertiary syphilis) 

Q. In which condition neuronophagia occurs? 

Ans: Polio and Rabies 

Q. What are globoid bodies? And in which condition are they found? 

Ans: These are small clusters found in lysosomal storage disorders (Krabbe's disease)

Q. In which disease Lewy bodies are found? 

Ans: Parkinson's disease

Q. What is a Lewy body made up of? 

Ans: Alpha-synuclein

Q. What stain is used to identify Flame cells? 

Ans: Bielschowsky Stain 

Q. What gives the cells a flaming appearance to the cells? 

Ans: Hyperphosphorylated Tau protein 

Q. How are Rosenthal fibers made? 

Ans: They are made of ubiquitin, alpha-beta crystallin, HSP and GFAP (In In P P) 

Also read: NEET PG High Yield Questions for Pathology

Multiple Choice Questions

Q. Ubiquitin deposition is seen in which of the following conditions? 

1. Alzheimer's disease 
2. Huntington's disease 
3. Meningioma 
4. FTLD 

Q. Lewy bodies are composed of? 

1. Tau protein 
2. Alpha-synuclein 
3. Beta plaques 
4. Actin 

Q. Hirano bodies are composed of? 

1. Tau protein 
2. Alpha-synuclein 
3. Beta plaques 
4. Actin 

Q. Which of the following is/ are seen in Alzheimer's disease? 

1. CAA 
2. Granulovacuolar degeneration 
3. Flame cells 
4. Hyperphosphorylated tau proteins 
5. Hirano bodies 
6. Neuritic plaques 

1. 1,2,4,5 
2. 1,2,4,5,6 
3. 1,2,3,4,5,6 
4. 2,3,4,5,6

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