Lecture 6: Timeline of Major Neurodevelopmental Processes, Disease and Research Models Flashcards
The CNS
among the earliest organ systems of the human body to begin its development prenatally and among the last to complete it postnatally
fastest growth rate is (4 pcw to 3 y)
Early Development of the Human CNS - embryonic phase
- Neurulation
- Patterning and segmentation
Early Development of the Human CNS - fetal phase
- Cortical growth via proliferation
- Neurogenesis, migration, polarization
- Sulci and gyri formation (continue after birth)
Early Development of the Human CNS - By Birth
Start and peak of gliogenesis (persist to some degree later on)
- Peak of synaptogenesis
Early Development of the Human CNS - After Birth
- Myelination
- Refinement and pruning of synapses
Timeline of Key Human Neurodevelopmental Processes - 10 years
substantial structural changes and reorganization of neural circuits paralleling the emergence of higher order cognition and complex behavior
Neurodevelopmental disorders and who is more affected
- Autism spectrum disorders (ASDs)
- Intellectual disability (XLID) e.g. Fragile-X, Rett, Down Syndromes
- Attention deficit hyperactivity disorder (ADHD)
males more suseptible
sexual dimorphic disorder
Neuropsychiatric disorders and who is more affected
- Schizophrenia
- Bipolar disorder
- Depression
Females are more prone
sexual dimorphic disorder
Neurodegenerative disorders
- Huntington disease
- Parkinson’s disease
- Alzheimer’s disease
- Significant aetiological heterogeneity within and between these conditions
→ Genetic factors and environmental stressors contribute to their comorbidity
Neurological Disorders Have Discrete Ages of Onset
Neurodevelopmental processes impacted in different brain disorders
in vitro model systems: Research Models in Neurological Research - Therapeutics
IPSCs
in vivo model systems: Research Models in Neurological Research - Therapeutics
animal models
ex vivo model systems: Research Models in Neurological Research - Therapeutics
brain organoids and assembloids
Creation of human brain organoids from human IPSCs via:
- Unguided differentiation
- Guided differentiation = bath application of morphogens to mimic normal development of specific brain regions
assembloids
assembly of regionalized organoids
- Cell migration
- Circuit formation
Modeling Neurological disorders: Huntington’s Disease
Modeling Neurological disorders: SHANK3 mutations
Modeling Neurological disorders: Timothy syndrome
