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Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging

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Abstract

Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer’s disease. Vascular contributions to cognitive impairment and dementia (VCID) include impairment of neurovascular coupling responses/functional hyperemia (“neurovascular uncoupling”). Due to the growing interest in understanding and pharmacologically targeting pathophysiological mechanisms of VCID, there is an increasing need for sensitive, easy-to-establish methods to assess neurovascular coupling responses. Laser speckle contrast imaging (LSCI) is a technique that allows rapid and minimally invasive visualization of changes in regional cerebromicrovascular blood perfusion. This type of imaging technique combines high resolution and speed to provide great spatiotemporal accuracy to measure moment-to-moment changes in cerebral blood flow induced by neuronal activation. Here, we provide detailed protocols for the successful measurement in neurovascular coupling responses in anesthetized mice equipped with a thinned-skull cranial window using LSCI. This method can be used to evaluate the effects of anti-aging or anti-AD treatments on cerebromicrovascular health.

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Acknowledgement

This work was supported by grants from the American Heart Association (to ST, MNVA, AC, and ZU), National Center for Complementary and Alternative Medicine (R01-AT006526 to ZU), National Institute on Aging (R01-AG047879 to AC; R01-AG038747), NIA-supported Geroscience Training Program in Oklahoma (T32AG052363), NIA-supported Oklahoma Nathan Shock Center (3P30AG050911-02S1), National Institute of Neurological Disorders and Stroke (NINDS; R01-NS056218 to AC), Oklahoma Shared Clinical and Translational Resources (to AY; NIGMS U54GM104938), Oklahoma Center for the Advancement of Science and Technology (to AC, ZU, and AY), the Reynolds Foundation (to ZU, AC, and AY), and the Presbyterian Health Foundation (to AC, ZU, and AY). We also acknowledge support from the Merit Review Award I01 BX002211-01A2 from the US Department of Veterans Affairs (to VG), William & Ella Owens Medical Research Foundation (VG), San Antonio Nathan Shock Center of Excellence in the Biology of Aging (2 P30 AG013319-21) (VG), and the Robert L. Bailey and daughter Lisa K. Bailey Alzheimer’s Fund in memory of Jo Nell Bailey (VG). This work was also supported by the National Research, Development and Innovation Office of Hungary (Grant No. K111923); the Bolyai János Research Scholarship of the Hungarian Academy of Sciences (No. BO/00327/14/5, to EF); and the EU-funded Hungarian Grant No. EFOP-3.6.1-16-2016-00008.

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Authors and Affiliations

  1. Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma, OK, 73104, USA

    Stefano Tarantini, Gabor A. Fulop, Tamas Kiss, Peter Toth, Anna Csiszar, Zoltan Ungvari & Andriy Yabluchanskiy

  2. Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA

    Stefano Tarantini, Gabor A. Fulop, Tamas Kiss, Peter Toth, Anna Csiszar, Zoltan Ungvari & Andriy Yabluchanskiy

  3. Faculty of Medicine & Faculty of Science and Informatics, Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary

    Tamas Kiss, Eszter Farkas & Dániel Zölei-Szénási

  4. Department of Cellular and Integrative Physiology, Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Veronica Galvan

  5. Department of Neurosurgery, University of Pecs, Pecs, Hungary

    Peter Toth

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  1. Stefano Tarantini
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  2. Gabor A. Fulop
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  3. Tamas Kiss
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  4. Eszter Farkas
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  7. Peter Toth
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  9. Zoltan Ungvari
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  10. Andriy Yabluchanskiy
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Correspondence to Andriy Yabluchanskiy.

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Tarantini, S., Fulop, G.A., Kiss, T. et al. Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging. GeroScience 39, 465–473 (2017). https://doi.org/10.1007/s11357-017-9980-z

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