Apologies for the lack of activity. I’ve been up to my ears in drywall and paint these last few days

Autism or autistic symptoms affect roughly 1 in 500 people and yet is still a relative mystery. A new study from the New York State Institute for Basic Research in Developmental Disabilities sheds some light on the growth and proliferation of neurons in autistic individuals. It was theorized that external growth factors in serum from autistic children would affect the growth of neuronal progenitor cells, thereby simulating early neurogenesis in autistic individuals. Neuronal prgenitor cells were grown in serum from autistic children and age-matched controls, giving some interesting results.

Results and details after the jump.

The development of the autistic brain is as mysterious as it is complex. Individuals with autism generally have larger brain masses and typically abnormally sized amygdala, hippocampus, and corpus callosum. On a smaller scale, the organization of minicolumns in the cerberal cortex is often altered. Cell size and density in the cerebellium and limbic system is often seen as well. These problems considered the result of errors early in brain growth, as early as 4-6 weeks into embryogenesis.

These developmental causes are the result of various extracellular factors such as neuropeptides, neurotransmitters, neurotrophins and other regulatory proteins. The difficult aspect about developmental diseases is that it causes a feedback loop. The brain is the largest producer of the factors required for its own growth. In ordinary individuals, this “pre-programmed” neurogenesis works like a clock. The early brain secretes the required chemicals to bootstrap itself into growth. This growth then creates new structures and new cocktails of growth factors, stimulating more growth in different regions. This feedback loop continues until the brain is fully formed.

Imagine the scenario similar to autistic children where the early brain has a minor genetic mutation causing a slight different cocktail of growth factors. This minor variation would result in the growth of a slightly different structure, causing a small change in the next cocktail of factors. Multiply these tiny changes over the course of brain’s developmental period and it is not difficult to see how a minor change can cause drastic developmental issues.

Unfortunately, there is no cellular or animal model available to study autistic neurogenesis. Similar results can be obtained by stimulating the differentiation of neuronal progenitor cells (NPCs) in the presence of autistic serum however. NPCs are cells that retain their ability to differentiate into either neurons or glial cells. NPC self-renewal or differentiation is strongly related to the variety of factors in the microenvironment surrounding NPCs. The team cultured NPCs in serum from autistic and age-matched controls.

Capillary zone electrophoresis was used to roughly measure the quantity of serum proteins and five main protein fractions (gamma, beta, alpha 1 and alpha 2 globulins, and albumins). It was found that the quantity of all proteins was roughly similar in both autistic sera and age-matched controls. A marker was introduced into all cells in the S phase of division. After 24h, cells containing the marker were counted. Cells grown in the autistic serum showed significantly less of the marker, indicating much less neural growth and division.

Despite slower division, experiments that measured growth of NPC colony formation showed significantly increased colony growth (in respect to physical area covered by the colony). Cell density was noticeably lower in autistic colonies than controls. NPCs in both cultures developed similar numbers of processes (dendrites, axons) per cell, but autistic cultures contained more cells with processes. The processes of autistic cells were also much longer. Furthermore, the types of cells containing processes tended towards small cells in autistic cultures while controls favored larger cells. Immunoblotting with mAb against synaptic vesicle protein (SV2) showed a 60% increase in immunoreactive material in autistic cultures over controls (which means more synaptic vesicles in autistic cells than controls).

An important thing to remember is that NPCs can either self-renew or differentiate into neurons/glia. The decreased proliferation of NPCs in autistic culture means the cells are not undergoing as much self-renewal, and therefore are experiencing increased differentiation into neurons/glia. The larger colony size and NPC lower cell density also points towards autistic NPCs favoring differentiation and migration over self-renewal. This tendency to favor differentiating and migrating out of the NPC neurospheres could have drastic consequences if experienced during early embryogenesis. The reduced self-renewal ability of autistic cells may also affect development later in life. It has recently been shown in research that neurogenesis is an important aspect of learning. The reduced ability for autistic individuals to renew their NPCs means they have a decreased neurogenesis ability later in life.

Autistic cultures favored smaller cells with more numerous and longer processes. It was noted that these most likely have a drastic affect on the organization and efficiency of the brain. Autistic cells also show greater synaptogenesis, potentially changing the entire balance of neurotransmitters in the brain relative to controls. The exact consequences of these changes, unfortunately, are difficult to predict. The team is continuing research on autistic serum, searching for factors that directly affect the cells as well as collecting geographically and age diverse samples.

B. Mazur-Kolecka et al, Altered development of neuronal progenitor cells after stimulation with autistic blood sera, Brain Research (2007), doi:10.1016/j.brainres.2007.06.084