Study of the electroretinogram of the Alzheimer\'s disease model mouse (3xTg-AD)

Author(s)

Gabriela Lourençon Ioshimoto

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Psicologia (IP/SBD)
• Defense date: 2011-03-02

Examining board members

Dora Selma Fix Ventura; Russell David Hamer; André Márcio Vieira Messias

• Advisor: Dora Selma Fix Ventura

Abstract

Objective: To evaluate electrophysiologically the function of the retina of the Alzheimer model mouse (3xTg-AD) comparing it with its control (b6;129-PS1) in a longitudinal study at six ages (2, 4, 6, 8, 10 e 12 months) Methods: Electroretinograms (ERGs) were recorded in 44 anesthetized mice 3xTg-AD and in 23 controls, with a contact lens electrode placed on the cornea, a reference electrode on the head and a ground on the tail. During a 30-40min duration session the mice were exposed to the following stimulation protocol: 1) Scotopic response Dark adaptation followed by flashes at the following intensities: 0,003; 0,03; 0,3; 3 e 30 cd.s/m2; 2) Periodic stimulation (30 cd.s/m2) at the temporal frequencies of 12, 18, e 30 Hz, under background light (30 cd/m2). Results: The ERGs showed two types of scotopic responses, which ocurred in both the control mice (b6;129- PS1) and the Alzheimer´s models (3xTg-AD). 13% of the controls and 72% of the Alzheimer´s models mice presented ERGs with oscillatory potentials (OPs) and b-wave implicit times within the expected range (45,31 ± 6,74 ms), while for the other groups the ERG presented a very delayed b-wave latency (111,73 ± 22,56 ms) and absence of OPs. Given these results, the control and experimental groups were subdivided into: b6;129 with OPs, b6;129 without OPs; 3xTg-AD with OPs e 3xTg-AD without OPs. An additional control group with 9 mice C57/B6 was included. Comparing the five groups, no difference was found in a-wave amplitude and latency. The b-wave amplitude also did not differ among the groups, but the latency of the b-wave for the groups b6;129 without OPs and 3xTg-AD without OPs, was twice as long as in the groups with OPs. The amplitudes of the five OPs, measured individually, did not show differences between controls and 3xTg-AD groups. For the periodic stimulation the amplitude of the first harmonic of the Fourier transform of the groups with OPs showed a clear difference between the control and the 3xTg-AD groups, both for the 12 Hz and for the 18 Hz stimuli. The results of the two control groups (b6;129 and C57/B6) were very close. The groups without OPs had responses always close to 10 V for the three frequencies of stimulation and showed phase delay for the first harmonic, indicating response slowing, compared to the other groups. Conclusions: We found that a sub-group of both triple transgenic (3xTg-AD) and control mice (b6;129) manifest strikingly slow scotopic ERGs that lack OPs. We hypothesize that these response feature may reflect alterations in bipolar, amacrine and ganglion cells. The sub-group of triple transgenic and control mice that exhibited OPs differed in their response to flicker. Alzheimer model had significantly lower flicker-response amplitudes than the controls, suggesting impaired retinal temporal processing. We propose that the flicker results are consistent with alteration in cone bipolar cells in the Alzheimer model mice (AU)

• FAPESP's process: 07/56844-1 - Electroretinography in 3xTg-AD mouse model of Alzheimer's Disease
• Grantee: Gabriela Lourençon Ioshimoto
• Support Opportunities: Scholarships in Brazil - Master