Module 6 (Part 2): Brain Damage and Neuroplasticity

• Parkinson's disease


  A progressive neurodegenerative disorder that primarily affects movement
• Parkinson's disease prevalence increases with age, with approximately 1% of individuals over the age of 55 being diagnosed
• Parkinson's disease tends to affect males slightly more frequently than females
• Symptoms of Parkinson's disease


  • Tremor or stiffness in the fingers and hands
  • Resting tremor
  • Muscular rigidity
  • Bradykinesia (slowness of movement)
  • Mask-like face
• The exact cause of the degeneration of dopamine-producing neurons in Parkinson's disease is not fully understood, but both genetic and environmental factors are believed to play a role
• The loss of dopamine neurotransmitters disrupts the delicate balance of neurotransmitters in the brain, leading to the motor symptoms characteristic of Parkinson's disease
• 1. DOPA (levodopa)


  The most commonly prescribed medication for Parkinson's disease, a precursor to dopamine that can cross the blood-brain barrier and be converted into dopamine, replenishing the depleted levels of this neurotransmitter
• Deep brain stimulation (DBS)


  A surgical procedure that involves implanting electrodes into specific regions of the brain, such as the subthalamic nucleus or globus pallidus, to deliver electrical impulses that help regulate abnormal neural activity associated with Parkinson's symptoms, providing relief from tremors, rigidity, and bradykinesia
• Huntington's disease (HD)


  A neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric symptoms
• Huntington's disease is inherited in an autosomal dominant pattern, meaning that a person only needs one copy of the defective gene to develop the disease
• Characteristics of Huntington's disease

  • Motor dysfunction (involuntary movements, muscle rigidity, coordination and balance difficulties)
  • Cognitive decline (problems with memory, reasoning, and judgment, often leading to dementia)
  • Psychiatric symptoms (depression, irritability, anxiety, psychosis)
• Symptoms of Huntington's disease


  • Complex jerky movements (chorea)
  • Symptoms typically appear between 30 to 50 years of age
• The mutation involves an abnormal repetition of the CAG [cytosine (C), adenine (A), and guanine (G)] nucleotide sequence within the HTT gene, leading to the production of an abnormal form of the huntingtin protein
• The mutated huntingtin protein disrupts normal cellular processes and ultimately leads to the degeneration of neurons in certain regions of the brain, particularly the basal ganglia and cerebral cortex
• There is currently no cure for Huntington's disease, and treatment focuses on managing symptoms, improving quality of life, and providing support for both individuals with HD and their families
• Multiple sclerosis (MS)


  A chronic autoimmune disorder characterized by the immune system attacking the central nervous system (CNS), specifically targeting the myelin sheath, which surrounds and protects nerve fibers
• Multiple sclerosis is a highly variable condition, with symptoms and progression differing significantly among affected individuals
• Symptoms of multiple sclerosis

  • Ataxia (lack of coordination)
  • Weakness
  • Numbness or tingling sensations
  • Tremor
  • Visual disturbances
• The exact cause of multiple sclerosis is not fully understood, but it is believed to involve a combination of genetic, environmental, and immunological factors
• While there is currently no cure for multiple sclerosis, various treatments are available to manage symptoms, modify disease progression, and improve quality of life for individuals with MS
• Studies have shown a higher concordance rate in monozygotic (identical) twins compared to dizygotic (fraternal) twins, suggesting a genetic component to MS susceptibility
• Multiple sclerosis occurs more frequently in females compared to males, with women being affected approximately three times more often than men
• Multiple sclerosis is more prevalent among individuals of Caucasian descent compared to other ethnic groups
• There is evidence to suggest that MS prevalence is higher in populations living in colder climates and at higher latitudes
• Alzheimer's disease


  A progressive neurodegenerative disorder characterized by a decline in cognitive function, including memory loss, impaired reasoning, and changes in behavior and personality
• Alzheimer's disease is ultimately fatal, often due to complications such as infections or malnutrition resulting from the progressive decline in cognitive and physical function
• Symptoms of Alzheimer's disease

  • Decline in memory
  • Emotional instability
  • Loss of speech function
  • Total dementia
  • Loss of ability to perform simple tasks
• Pathological features of Alzheimer's disease (at autopsy)

  • Amyloid plaques
  • Neurofibrillary tangles
  • Loss of cells in specific brain regions (hippocampus, amygdala, entorhinal cortex)
• Treatments for Alzheimer's disease


  • Increase acetylcholine function
  • Reduce amyloid plaques
  • Treatments based on relationship between Downs and Alzheimer's
  • Treatments directed toward misfolded protein hypotheses
• Kindling Model of Epilepsy

  An experimental procedure used in neuroscience research to study the mechanisms underlying epilepsy, particularly the development and progression of seizures
• Procedure of the Kindling Model

  1. Electrical brain stimulation

  2. Development of seizures

  3. Progression to generalized convulsions

  4. Other induction methods (chronic administration of convulsive drugs)

  5. Permanent procedure
• Utility of the Kindling Model in studying epilepsy

  • Mimicking human epilepsy
  • Investigating physiological changes
  • Modeling mechanisms of epileptogenesis
• Transgenic Mouse Models of Alzheimer's Disease

  Mouse embryos are injected with genes that accelerate amyloid development, typically genes associated with familial forms of Alzheimer's disease, resulting in mice that overproduce beta-amyloid protein and develop amyloid plaques in their brains, mimicking the pathology seen in Alzheimer's disease
• Unlike in humans, these transgenic mice do not develop neurofibrillary tangles, another hallmark of Alzheimer's pathology
• While transgenic mice develop amyloid plaques, they do not exhibit memory impairment, which is a key feature of Alzheimer's disease in humans
• Despite the limitations, transgenic mouse models have been invaluable in Alzheimer's disease research, particularly in the development and testing of potential therapies
• MPTP Mouse Models of Parkinson's Disease


  MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin that selectively damages dopamine-producing neurons in the brain, particularly those located in the substantia nigra pars compacta, and has been used to develop mouse models of Parkinson's disease
• MPTP mouse models of Parkinson's disease have been instrumental in advancing our understanding of the disease and testing potential therapeutic interventions
• Mice treated with MPTP exhibit similar neurodegenerative changes observed in humans and primates, including the loss of neurons in the substantia nigra and a subsequent reduction in dopamine levels, as well as motor symptoms characteristic of Parkinson's disease
• MPTP


  1. methyl-4-phenylpyridinium, a potent neurotoxin that selectively destroys dopamine-producing neurons in the substantia nigra