Early on, researchers found that if they sprinkled Brain Derived Neurotrophic Factor onto neurons in a petri dish, the cells automatically sprouted new branches, producing the same structural growth required for learning — and causing me to think of BDNF as Miracle-Gro for the brain.
— John Ratey, Spark

Growth Factors: a group of proteins that stimulate certain cells to grow and divide. In animals, secreted into the bloodstream. (Brooker, 186)

Any of various chemicals that have a variety of important roles in the stimulation of new cell growth and cell maintenance. They “bind” to the cell surface on “receptors." Specific growth factors can cause new cell proliferation and the "migration" of cells, and play a role in wound healing. (OxfordMed) Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. (NCIt)


Cyclic AMP (Adenosine Monophosphate): a small molecule that binds to key proteins inside a cell that trigger a whole family of molecular responses throughout the cell. The “hormone” “epinephrine” produces a brief biochemical change at the surface “membrane” of cells that gives rise to a more enduring change inside the cells. That longer lasting change is brought about by an increase in the amount of cyclic AMP inside those cells. (Kandel, 226-227)

Cyclic AMP Response Element-Binding Protein (CREB): “transcription factor” best known for its involvement in learning and memory. (PubMed, 15982754) A regulatory protein found in the “nucleus” of a neuron that, once activated by “protein kinase A,” binds to a “promoter.” A key component of the switch that converts short-term facilitation of “synaptic” connections (between neurons) to long-term facilitation and the growth of new connections. CREB is essential to the long-term strengthening of synaptic connections. The “activation” of CREB leads to the “expression” of “genes” that changes the function and the structure of the cell. (Kandel, 263-264) Emerging evidence suggests that CREB activity has very different roles - sometimes beneficial, sometimes detrimental - depending on the brain region involved. (Activation) of CREB in the “hippocampus” by “antidepressant” treatments could contribute to their therapeutic efficacy. By contrast, activation of CREB in the “nucleus accumbens” and several other regions by "drugs of abuse" or "stress" mediates certain aspects of “drug addiction,” and depressive and anxiety-like behaviors. (PubMed, 15982754)

CREB-1: the form of CREB that activates gene expression. Repeated "stimulation" causes protein kinase A to move to the nucleus where it activates CREB-1. (Kandel, 264)

CREB-2: the form of CREB that suppresses gene expression. Repeated stimulation causes 'MAP kinase' to move to the nucleus where it inactivates CREB-2. Thus long-term facilitation of synaptic connections requires not only a switching on of some genes, but also the switching off of others. (Kandel, 264)

Cytoplasmic Polyadenylation Element-Binding Protein (CPEB): located at all synapses of a neuron.  Activated by “serotonin.” Required at the synapses to maintain “protein synthesis” and the growth of new synaptic terminals. (Kandel, 272) Dr. Eric Kandel’s lab has discovered that this protein plays a key role in “Aplysia’s” “long-term memory” retention by taking a form distinctly like that of a “prion.” It is the first time anyone has shown that a prion-like protein plays a role in normal physiology. (SAM, Oct/Nov 2007, 37)

Fibroblast Growth Factor (FGF-2): stimulates "progenitor cells" to produce "neuroblasts." (Kolb, 195) A protein that is produced and released in the body and the brain when tissues are stressed. FGF-2 helps create more "blood vessels" and other "tissues." Involved in initiating the process of stem-cell division that is necessary for "neurogenesis," and it also encourages “long-term potentiation” and the formation of memories. (Ratey, 279)

Growth Factor Receptors: a class of cell surface proteins that bind to “extracellular” molecules triggering “intracellular” “signaling pathways” that activate various cellular responses such as cell proliferation and/or “differentiation.” (NCIt)

Insulin-like Growth Factor (IGF): a protein, produced by moving muscles, that travels through the bloodstream and into the brain. (Ratey, 5) A protein made by the body that stimulates the growth of many types of cells. IGF is similar to “insulin” (a hormone made in the pancreas). There are two forms of IGF called IGF-1 and IGF-2. Higher than normal levels of IGF-1 may increase the risk of several types of "cancer." IGF is a type of growth factor and a type of “cytokine.” (NCIt) In the brain, IGF-1 doesn’t have as much to do with getting energy into the cells as it does with regulating “glucose” throughout the body. Exercise increases IGF-1 which helps insulin manage glucose levels. In the hippocampus, IGF-1 increases “LTP,”  “neuroplasticity,” and neurogenesis. It’s another way exercise helps our neurons bind. (Ratey, 78) Has a major, but not absolute, dependence on “growth hormone.” It is believed to be mainly active in adults, in contrast to IGF-2 which is a major “fetal" growth factor. (MeSH)

Kinase: any of various “enzymes” that “catalyze” the transfer of a "phosphate group" from “ATP” to another molecule (thereby modifying the target molecule’s function). (Oxford) A type of enzyme that causes other molecules in the cell to become active. Some kinases work by adding chemicals called 'phosphates' to other molecules, such as “sugars” or proteins. Kinases are a part of many cell processes. Some cancer treatments target certain kinases that are linked to cancer. (NCIt) The transfer process is referred to as “phosphorylation.” (Kandel, 446)

Protein Kinase A: composed of four units, two regulatory and two catalytic. The catalytic units are designed to carry out a process that activates some proteins and inactivates others (phosphorylation), but the regulatory units normally ‘sit’ on them and inhibit them. The regulatory units contain sites that bind cyclic AMP. When the concentration of cyclic AMP in a cell increases, the regulatory units bind the excess molecules. This action changes their shape and causes them to fall off the catalytic units. Once freed, the catalytic unit of protein kinase A enhances the release of the “glutamate.” (Kandel, 228-229) Cyclic AMP activates protein kinase A which ‘phosphorylates’ (adds phosphate to) specific cellular proteins, changing their “conformation” or function and thus causing a cellular response. (Norman, 6/10/09)

Neurotrophic Factors: chemical compounds that act to support growth and differentiation in developing neurons and may act to keep certain neurons alive in adulthood. (Kolb, 195) Family of growth factors produced by peripheral target tissues as well as the “nervous system,” which are critical to neuronal growth, regeneration, survival, and differentiation. (NCIt) ‘Trophic’ is having to do with the process of nutrition. (Used) in the sense that it stimulates neurons to grow dendrites and synapses, and in some cases, promotes the survival of neurons. (Kolb, 512) Also referred to as ‘neurotrophin.’

Brain-Derived Neurotrophic Factor (BDNF): a nerve growth factor that plays a crucial role in reinforcing “plastic” changes made in the brain in the “critical period.” When we perform an activity that requires specific neurons to fire together, they release BDNF. This growth factor consolidates the connections between those neurons and helps to wire them together so they fire together reliably in the future. Also promotes the growth of “myelin.” During the critical period, it turns on the “nucleus basalis.” Later, it helps close down the critical period. (Doidge, 80) A protein produced inside nerve cells when they are active. It serves as ‘Miracle-Gro’ for the brain, fertilizing brain cells to keep them functioning and growing, as well as spurring the growth of new neurons. (Ratey, 276)

Nerve Growth Factor (NGF): a protein responsible for promoting nerve growth. (Doidge, 79) One of a family of (neurotrophic factors) that induce the survival and proliferation of neurons. Plays a role in the maintenance of “sympathetic” and “sensory” neurons. (NCIt) The first neurotrophic factor discovered. (It was found) in the "peripheral nervous system." (Kolb, 512) Discovered in the early 1950s due to its survival and growth-promoting effects on neurons. (PubMed, 2504526)

Vascular Endothelial Growth Factor (VEGF): an important signaling protein produced and released in the body when tissues are taxed and there is not enough blood flow to fuel the demand. VEGF signals other cells to start dividing to make more blood vessels. Recently, scientists have learned that VEGF is also produced in the brain and is involved in cementing memories. (Ratey, 281)