The question is based on the paper: 1. 35 Points The following figure is from th

Question

The question is based on the paper: 1. 35 Points The following figure is from the Ahmed paper presented in class. Why was this figure included? (5 points) What question was being asked in Figures B, C, D and E (5 points each Describe the strategy behind making the animal models in Figure 5E-address the question why were these mice used 5 points) and how were they made (5 points)? Be sure to explain each column of data and why the animal model used was effective to address each question. human neurons human neurons 7 150 150 IBO ANDA NMDA mouse neurons PS mouse P5 mouse

Explanation / Answer

This figure was included to decipher the mechanism involved in the inflammation induced sensitization. In this figure specifically role of GRK2 in inflammation induced sensitization is studied.

GRK2 is known to regulate phosphorylation and sensitization of GPCRs.

The GRK2 level is less in newborn mice and newborn are have been observed to be more sensitive.

Thus it was observed that inflammation- decrease GRT2 level in neuron- group I mGluR mediated exitotoxicity is enhanced.

In the figure B, the question which is answered is that when GRT2 is over expressed in human neuron what effect it will.have on activation of NMDA in presence and absence of mGluRs.

Figure C, the question which is answered is the response of GRK2+/- and GRK2+/+ to exitotoxicity.

Figure D, confirmation of the test done in figure C.

As these PRP mouse have less GRT2 quantuty restricted to neurons, and less GRT2 shows higher sensitivity to ibotenate. So these animals were used.

Inflammation sensitizes to exitotoxic neurodegeneration and this involves downregulation of GRT2. And young mice with less GRT2 levels are used.

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