Ch7-Lifespan Development

Development of the Nervous System

• Nervous system development involves seven key processes: neurogenesis, migration, differentiation, synaptogenesis, apoptosis, synaptic rearrangement, and myelination.
• Experience and epigenetics play a role in development, affecting aging as well.
• Ongoing neurogenesis, vascular dementia, stress and Alzheimer's disease are factors linked with aging of the nervous system.

Stages of Development

• Zygote: A fertilized egg, a single cell.
• Blastocyst: A hollow sphere of stem cells with pluripotential capabilities.
• Gastrula: A three-layered form resulting from a partially differentiated blastocyst.
• Embryo: Composed of three layers—ectoderm, mesoderm, and endoderm.
• Fetus: Recognizable in relation to its mature form.

Neurulation

• Neurulation involves the dorsal epithelial layer (ectoderm) thickening to form a neural plate.
• The neural plate folds to create a neural groove and neural tube, which ultimately forms the central nervous system.
• This occurs around 18-22 days.

Cells of the Nervous System

• Neural crest cells break off during neurulation and migrate, forming the peripheral nervous system, guided by chemical signals.
• Sensory organs originate, at least partly, from sensory placodes. These include olfactory, lens, trigeminal, geniculate, epibranchial, petrosal, and otic placodes.

Cell Migration

• Cells of the neural crest migrate to their final destinations guided by chemical signals, contributing to the peripheral nervous system's structure.
• Important to note that migration occurs in waves, with different waves creating different regions of the brain.

Differentiation

• Dividing pluripotent cells differentiate into non-dividing neuroblasts and glioblasts.
• The cells mature into specialized neurons or glial cells.
• Remaining ventricular cells differentiate into ependymal cells lining the ventricles and spinal cord.
• Different cell types undergo different processes depending on their location and function.

Synaptogenesis

• Synaptogenesis involves the growth of axons, dendrites, and synapses.
• Filopodial structures from growth cones extend and contract.
• Target cells release chemical labels that attract growing axons.
• Pioneer growth cones interact with NCAMs to guide subsequent neurons' growth, creating stereotyped axonal paths and making a complex structure in a consistent way.

Apoptosis

• Exuberant cell proliferation in early development is followed by programmed cell death (apoptosis).
• Cells not contacting their appropriate target undergo apoptosis.
• Glial cells can undergo apoptosis, and progenitor cell careers end due to apoptosis.

Synaptic Rearrangement

• Neurons that fire together wire together (Hebbian principle).
• Synaptic contacts become more focused over time.
• Synaptic density peaks around one year of age and then decreases.
• Throughout prenatal and postnatal life, and across the different stages of development, patterns of synaptic contact shift.

Myelination

• Myelination, the formation of myelin sheaths, starts around 24 weeks after conception.
• It begins in the spinal cord and progresses to other brain regions.
• A high-intensity phase of myelination occurs in the early postnatal period.
• Myelin sheath formation occurs in stages and may vary across regions.

Environmental Influences

• Environmental enrichment promotes thicker cortex, more dendrites, and more synapses.
• Visual deprivation results in fewer synapses and spines in primary visual cortex, leading to deficits in visual perception.
• Experience significantly shapes the functional organization of the brain, particularly in the visual cortex.

Aging

• Aging continues neurogenesis and migration in specific areas (hippocampus, caudate nucleus, olfactory bulb).
• Age-associated memory impairment (AAMI) varies from mild cognitive impairment to profound dementia.
• Cognitive function remains intact until advanced age in most individuals.
• Age-related changes can affect the ability to acquire and store new information.
• Factors such as education and profession may influence AAMI risk factors, while mood and depression are significant correlates to cognitive decline.

Alzheimer's Disease

• Alzheimer's disease is the most common form of age-related dementia.
• It involves the accumulation of amyloid plaques and neurofibrillary tangles.
• The disease often starts in the hippocampus and overlying cortical areas and progressively spreads.
• Genetic factors, like mutations in amyloid precursor protein genes or certain alleles of the apolipoprotein E gene, influence both early-onset and late-onset types.
• Early-stage symptoms often involve difficulties with memory, language, and identification of objects or words.
• In later stages, patients may become mute and severely disabled.

Epigenetics

• Epigenetics describe how experiences affect gene expression throughout a lifespan.
• DNA methylation, adding methyl groups to DNA, can turn off genes in a stable way.
• Histone acetylation affects how tightly DNA is wrapped around proteins and is involved in gene activity, which is affected by environmental factors.
• There are also wider influences, including development, environmental chemicals, pharmaceuticals, diet, and aging.

Vascular Dementia

• Vascular dementia can be caused by larger infarcts (>50ml) or smaller lacunar infarcts (1ml).
• Risk factors include hyperlipidemia, diabetes mellitus, hyperhomocysteinemia, smoking, elevated C-reactive protein, cerebral amyloid angiopathies.

Hippocampus Atrophy

• Chronic stress and elevated glucocorticoids can lead to hippocampal atrophy.
• This is likely due to shrinkage in dendritic arborization.