Regenerative Medicine & Biotechnology: Brain Repair (Focus on Neurogenesis)

These flashcards cover the anatomy, history, molecular regulation, and clinical implications of adult neurogenesis and brain repair as discussed in the lecture.

Cerebral Cortex Surface Area Scale

The relative increase in surface area across species, specifically $1:100:1000$ for the mouse, macaque monkey, and human, respectively.

Prefrontal Cortex

A brain region present in both human and macaque brains that has no counterpart in the mouse brain.

Neocortical Column

The basic organizational unit of the neocortex, with a diameter of $0.5\,mm$ containing approximately $10,000$ neurons.

Pyramidal neurons

Large output neurons located in the fifth layer of the six-layered neocortex.

S. Ramon y Cajal (1913)

A neuroscientist who originally proposed that adult nerve paths are 'fixed, ended, immutable' and that nothing may be regenerated.

Joseph Altman (1962)

Researcher who used autoradiography and $[^{3}H]$ Thymidine to provide early evidence of new neuron formation in the adult rat brain.

$[^{3}H]$ Thymidine

A radioactive nucleotide that incorporates into DNA strands during replication, used to visualize and identify dividing cells.

Neural Stem Cells (NSCs)

Adult mammalian cells capable of self-renewal and differentiation into neurons and glial cells (astrocytes and oligodendrocytes).

Subventricular Zone (SVZ)

A neurogenic niche located in the wall of the lateral ventricle where most neurons are generated in the developing and adult brain.

Subgranular Zone (SGZ)

A neurogenic niche in the hippocampal formation (specifically the dentate gyrus) where neurons are born locally.

Rostral Migratory Stream (RMS)

The pathway through which neural progenitor cells migrate from the subventricular zone to the olfactory bulb.

PSA-NCAM

Polysialylated neural cell adhesion molecule; used to identify chains of tangentially migrating neurons destined for the olfactory bulb.

Types A, B, and C Cells (SVZ)

The three organized cell types of the SVZ; Type A cells are closest to the ependymal layer, Type B cells form the astrocytic ribbon, and Type C cells are located near the myelin layer.

Huntington's Disease (SVZ effect)

Characterized by striatal cell loss but an increase in SVZ thickness and higher numbers of Type A, B, and C cells.

Parkinson's Disease (SVZ effect)

Involves a reduction in dopaminergic input from the substantia nigra, leading to the death of receptor-rich Type C cells and fewer progenitor cells.

Alzheimer's Disease (SVZ effect)

Characterized by an imbalance in $\alpha$ and $\beta \gamma$ secretases, leading to $\beta$-amyloid accumulation and cell death in the SVZ.

Exercise and Neurogenesis

Physical activity (running) is shown to increase cell proliferation and neurogenesis in the adult mouse hippocampus and improve spatial learning.

Rita Levi-Montalcini

Nobel Prize winner (1986) who discovered Nerve Growth Factor (NGF), the first protein growth factor identified by studying chick embryos and mouse sarcoma.

Positron Emission Tomography (PET) scan

A nuclear medicine imaging technique using radioactive tracer isotopes to produce 3D images of functional processes, such as dopamine distribution in Parkinson's.

[18F]-dopa

A radioactive tracer used in PET scans to label dopamine (DA) nerve terminals and monitor degeneration in Parkinson's disease.

Neurosphere

A non-adherent spherical cluster of neural stem cells cultured in vitro that can be differentiated into neurons and glial cells.

Nigro-striatal pathway

The neuronal pathway projecting from the substantia nigra to the caudate nucleus and putamen (striatum) that degenerates in Parkinson's patients.

Fluorodopa PET uptake

A measurement used to assess the success of fetal dopamine neuron transplants; successful grafts show increased uptake in the putamen.

Epigenetic control of NSCs

The regulation of neural stem cell fate through extrinsic and intrinsic factors like chromatin remodeling, DNA methylation, and histone modifications.

Induced Pluripotent Stem Cells (iPSC)

Adult fibroblast cells reprogrammed into pluripotent states using factors like KLF4, SOX2, c-Myc, Nanog, Oct-3/4, and LIN-28.

Neurogenesis Signaling Pathways

Key molecular pathways including Notch, Shh (Sonic Hedgehog), and $\beta$-catenin that regulate the birth and differentiation of neurons.

Nestin

An intermediate filament protein used as a marker for neural stem/progenitor cells.