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Neurovascular coupling preserved in a chronic mouse model of Alzheimers disease: Methodology is critical.

By Paul S. Sharp, Kam Ameen-Ali, Luke Boorman, Sam Harris, Stephen Wharton, Clare Howarth, Peter Redgrave, Jason Berwick

Posted 22 Nov 2018
bioRxiv DOI: 10.1101/474916 (published DOI: 10.1177/0271678X19890830)

Neurovascular coupling is the process by which neural activity causes localised changes in cerebral blood flow. Impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimers disease (AD), and if so, could serve as an early biomarker of cerebral pathology. We have established an anaesthetic regime in which evoked hemodynamic responses are comparable to those in awake mice. This protocol was adapted to allow repeated measurements of neurovascular function over three months in the hAPP-J20 mouse model of AD (J20-AD) and wild-type (WT) controls. Animals were 9-12 months old at the start of the experiment, which is when deficits due to the disease condition would be expected. Mice were chronically prepared with a cranial window through which optical imaging spectroscopy (OIS) was used to generate functional maps of the cerebral blood volume and saturation changes evoked by whisker stimulation and vascular reactivity challenges. Unexpectedly, the hemodynamic responses were largely preserved in the J20-AD group. This result failed to confirm previous investigations using the J20-AD model. However, a final acute electrophysiology and OIS experiment was performed to measure both neural and hemodynamic responses concurrently. In this experiment, previously reported deficits in neurovascular coupling in the J20-AD model were observed. This suggests that J20-AD mice may be more susceptible to the physiologically stressing conditions of an acute experimental procedure compared to WT animals. These results therefore highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.

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