The Neurobiology of Down syndrome

                                                       The Neurobiology of Down syndrome

            Down syndrome is the most common non-hereditary cause of metal retardation. It is estimated that there are 350,000 people living with Down syndrome (DS) in the United States. The cause of DS is still unknown, however the physical and mental abnormalities that is causes are a result of the tripling of the 21st chromosome, hence its technical name Trisomy-21. Downs people are more likely to have congenital heart defects, childhood leukemia, thyroid conditions, and Alzheimer's disease. All cases of DS are accompanied by mental retardation, defined as having an IQ below 75. Mental retardation in Downs people is caused by imperfections in the structure of their neurons (E). Alzheimer's Disease (AD) becomes prevalent later in life, as virtually all Downs people develop AD by age 40 (C). I will explain the most current theories as to how these defects in the structure of neurons result in mental retardation and eventually AD later in life, as well as how this research is relevant in the real world.
            It is widely agreed upon that DS alters neurons in the brain and further, that these abnormal neurons are the cause of the inability to learn and obtain information at the level of a an average person. The IQ of an average person is about 100. To be considered mentally retarded, a person must have an IQ under 75. Regardless of why (as it is an ongoing debate between researchers), it is the less than fluid translation of signals going from the axon, across the synapse, to the dendrite, and to another axon that causes mental retardation in Downs people (B).
          One proposition suggests that a lack of cells become neurons during fetal development. This theory specifies that it is the mis-shapen dendrites that are to blame for faulty connections between axons and dendrites. It is essential for signal translation that the dendrite is in its proper form to successfully uptake the neurotransmitter (E). Because the neurotransmitter carries the signal in a chemical form, it is the job of the dendrite to transform the signal into an electrical signal in order for the signal to be successfully passed to the axon and continue the message transfer. More specifically, The Andrew Chess lab argues that the tripling of the 21st chromosome also triples the amount of Dscam protein. The Dscam protein is responsible for essentially "naming" each cell and allowing for communication between cells. Chess believes that the extra Dscam protein prohibits normal cell "conversations" from happening, therefore resulting in metal retardation (E).
            Another philosophy as to what causes mental retardation in DS examines faulty neurons in the hippocampus. According to researchers at Stanford University, it is the synapses that are defective in DS. This data comes from studies done using the Ts65Dn mouse model - a mouse structured to have DS through the tripling of the 16th chromosome. By studying this mouse model, the researchers have discovered "That both the presynaptic elements and the postsynaptic elements are enlarged in many brain regions" including the motor cortex, sensory cortex, and hippocampus (D). The reason that they believe the disfigured axons and dendrites play a large part in causing metal retardation in Downs people is because the function of the hippocampus is primarily memory - ie. the center for learning.
           The researchers were able to prove that neuronal function was compromised in the hippocampus through electrophysiological studies - detecting activities in the hippocampus through current in the neurons, which represents learning. The researchers considered synaptic plasticity as learning, but discovered that their Ts65Dn mouse model had suppressed plasticity in its hippocampus, thus its inability to learn and retain information. They further attributed the suppressed plasticity of neurons in the hippocampus to excess inhibition at the synapses. They suggested that the inhibition could be the product of too much inhibitory neurotransmitter being released from the presynaptic terminal into the synapse, thus preventing the dendrite from picking up all of the chemical signal from the synapse (D).
            Another consequence of the tripled 21st chromosome and abnormality of the hippocampus is the development of Alzheimer's disease. AD sets in by age 40 to nearly all Downs people, and further demise of mental capacity develops as age approaches 60 years. Scientists have found "Alzheimer's disease-like neuropathology [b-amyloid (Ab) plaque, neurofibrillary tangles and neuronal loss]" in mature DS brains (A). It is especially interesting because the plaques and tangles that characterize AD are found in the hippocampuses of DS brains, which is the starting point for nearly all cases of AD. Other studies suggest that "Alzheimer's disease could be considered a late onset form of Down syndrome" as DS causes the same brain defects. Both AD and DS are characterized by plaque build-up which causes neuron death and memory loss (F). Although the onset of AD occurs at different points in the lives of people with DS and those without, the similarities are helping both groups. Scientists have learned that the gene for AD may be contained in the 21st chromosome, and doctors may use the medications designed for AD in younger Downs people who show early symptoms of AD.
            Although these findings may eventually lead researchers to find a repair for the faulty neuron connection caused by Down syndrome, the research through today is not of much use to the general public. Although researchers have identified dysfunction in the neurons, they still are not sure whether the problem is the synapse, the dendrite size, or the dendrite spines. After all, Down syndrome is a genetic syndrome that stays with the affected person through his or her entire life. Without a cure for the deficient neurons, what does the neurobiology of Down syndrome do for anyone?
             Growing up with my Downs brother has not been easy for my parents and me. For many years, my parents wanted to think nothing of what made George different from us. Having lived with George for the past 16 years has secured my thoughts about him as a person and erased the need to highlight the differences each day. However, going through the neurobiology of his syndrome has helped remind me that the differences between George and I are not his fault or anyone else's. The differences are biological, and out of our control. When he cannot tie his shoes or is afraid to walk in the dark, it is comforting to pull myself away and know that this is no ones fault. It is not George's conscious choice to be noncooperative, it the deficient connections between his neurons that disable him from functioning as we do. The science behind this syndrome gives me patience and understanding to continue helping George in every way, to see him achieve what others never thought possible.
             I believe that publicizing the neurobiology behind conditions like DS will only help others to appreciate the differences and take away the blame. Understanding how the deficient neurons prohibit normal processing of inputs and normal control of outputs would help others appreciate the marvel it is that DS people can function as well as they do (some evening completing college and living on their own). Downs people are some of the most pleasant people that I have ever encountered. In my opinion, understanding their condition may help others get past the stereotypes associated with metal retardation and help them appreciate these wonderful people for who they are.

  
                                                                                            Works Cited
(A) Engidawork, Ephrem, and Gert Lubec. "Molecular Changes in Fetal Down Syndrome Brain." Journal of Neurochemistry 84 (2003): 895-904. Wiley Interscience. Web. 28 Apr. 2010. <http://www3.interscience.wiley.com/cgi-bin/fulltext/118870862/PDFSTART>.
(B) "National Down Syndrome Society - Down Syndrome Fact Sheet." National Down Syndrome Society - Welcome to NDSS. 2010. Web. 28 Apr. 2010. <http://www.ndss.org/index.php?option=com_content&view=article&id=54&Itemid=74>.
(C) Patoine, Brenda. "Mental Retardation: Struggle, Stigma, Science - Dana Foundation." Brain and Brain Research Information - Dana Foundation. 1 Apr. 2005. Web. 06 May 2010. <http://www.dana.org/news/cerebrum/detail.aspx?id=808>.
(D) "Research: FAQs." Welcome to Down Syndrome Research and Treatment Foundation. 2010. Web. 28 Apr. 2010. <http://www.dsrtf.org/research-faq.htm>.
(E) Svendsen, C. N., Andrew Chess, and Roger H. Reeves. "Down Syndrome, Microencephaly, Small Brain, Brain Development." History of Down Syndrome and It's Treatment: Don't Be Disheartened, It's Getting Better All the Time. 2010. Web. 06 May 2010. <http://www.cdadc.com/ds/earlydsbrain.htm>.
(F) University of South Florida Health. "Studies Demonstrate Link Among Alzheimer's Disease,
Down Syndrome and Atherosclerosis." ScienceDaily 15 January 2010. 6 May 2010
<http://www.sciencedaily.com_ /releases/2010/01/100115182639.htm>.