User:Lilia Patino

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Lilia Patino (an artistic interpretation)

I work in the Your Lab at XYZ University. I learned about OpenWetWare from professor, and I've joined because required by professor.

Education

  • 2009, BS, Loyola Marymount University

Biology 598

Lithium delays progression of amyotrophic lateral sclerosis [1]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that usually leads to death within three to five years from diagnosis. Studies were done using wildtype and G93A mice treated with lithium and saline. In the study conducted it was found that doses of lithium delay disease progression in humans affected by ALS and increases the lifespan of patients. They found that lithium increases the number of neurons in lamina VII and reduces necrosis in mitochondrial vacuolization.

Figure two [2] shows the neuroprotective effects of lithium on medium size lamina VII neurons. Part a shows the micrographs of the H&E –stained lamina VII neurons which were selected for size specificity. These micrographs show that there is an increase in neuron number when lithium is present in the G93A mice as oppose to saline being present in the G93A mice. In figure b, the graph is used to indicate the number of neurons within a Lamina VII section. It shows that when saline is present, there is a severe loss of neurons in the G93A mice compared to the wild type. On the other hand, the G93A mice treated with lithium showed a higher number of lamina VII medium size neurons when compared both to the saline-treated wild type mice and the lithium-treated wildtype mice. Therefore, the net increase in the number of neurons occurred only when lithium was administered to the G93A mice. Figures 2c – e confirm the results stated above by using immunostaining. Figure 2c is the staining used to visualize neurons specific to the protein Gephyrin. This staining shows that there is a higher density of Lamina VII medium sized neurons only when lithium is present in the G93A mice as oppose to saline being present. Figure 2d is a graph conforming the results in part 2c. It shows that the number of neurons in Gephyrin increased only when lithium was administered to the G93A mice. In Figure 2e immunoblotting was used to detect the presence of the protein Gephyrin and it was found that Gephyrin is expressed more in lithium-treated G93A mice and wildtype than in saline-treated G93A mice and wildtype. The second part of Fig 2e graphically confirms the results from the first part of Fig 2e. This graph demonstrates that there is a higher density of Gephyrin when lithium is administered as oppose to saline.

Figure 3 [3] shows the effects of lithium administration on motor neuron mitochondria. In pictures a-h, arrows are pointing to the mitochondria of motor neurons from the spinal cord. 3a and 3b show motor neurons from the spinal cord of wildtype mice treated with saline and 3c-d show mitochondria from the spinal cord of wildtype mice treated with lithium. Figure 3e and 3g demonstrate mitochondria of G93A mice treated with saline while 3f and 3h show mitochondria of G93A mice treated with lithium. In figure 3g, the arrow heads are pointing to mitochondrial vacuolization, defined as slow necrosis, in which mitochondrial swelling occurs, causing motor neurons to appear to be filled with vacuoles. Fig 3f and 3h show a decrease/absence in vacuolization due to lithium treatment, normalizing the size of mitochondria motor neurons in the spinal cord as shown in figures 3i and 3j. Figure 3i is a graph representation of 3f and 3h showing that the mitochondrial diameter in the cervical spinal cord is smaller in both the wildtype and G93A mice that are treated with lithium compared to the wildtype and G93A mice treated with saline. Figure 3j shows similar results to 3i, only difference is that it is looking at the mitochondria diameter in the lumbar spinal cord. The fact that lithium treated wildtype and G93A mice show a smaller diameter of mitochondria shows that there is less swelling and therefore less vacuoles are present in the mitochondria. As shown in figure 3d, the size of the mitochondria is decreased due to the lithium treatments not only in the G93A mice but also in the wildtype mice. Lithium was also shown to increase the number of normal mitochondria in both the wildtype and G93A mice as seen in 3k and 3l. Figure 3k is a graphical representation of the number of mitochondria in the cervical region of the spinal cord. As shown, both the wildtype and G93A mice that were treated with lithium showed a higher number of mitochondria than the wildtype and G93A mice treated with saline. The number of mitochondria in the lumbar region of the spinal cord also showed an increase in number in both the wildtype and G93A mice treated with lithium while those treated with saline showed a lower number of mitochondria (fig 3l). These results are important and encouraging based on the fact that the loss of mitochondria can be a risk for drugs that act to enhance autophagy, which aids in the destruction of unhealthy neurons.

Figure 4 [4] shows the effects of lithium on autophagy. Degenerating mitochondria was found within authophagic vacuoles and autophagosomes within the motor neurons of the G93A mice. This finding led to the hypothesis that lithium can improve motor neuron survival by activating autophagy. Beclin and LC3 (light chain 3) were used as autophagy markers to detect autophagy vacuoles. As shown in figures 4g and 4h, the number of beclin and LC3 was increased by lithium. Figure 4g shows that there is an increase in the amount of beclin-positive autophagolisosome in the wildtype and G93A mice treated with lithium as oppose to saline. Similarly, figure 4h shows and increase in the amount of LC3-positive autophagolisosome in both the wildtype and G93A mice treated with lithium. By counting the beclin and LC3 markers as well as the vacuoles, lithium was found to increase autophagic vacuole formation.

Publications

  1. Goldbeter A and Koshland DE Jr. An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6840-4. PubMed ID:6947258 | HubMed [Paper1]
  2. JACOB F and MONOD J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961 Jun;3:318-56. PubMed ID:13718526 | HubMed [Paper2]
    leave a comment about a paper here
  3. ISBN:0879697164 [Book1]
All Medline abstracts: PubMed | HubMed

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