A Preliminary Study Targeting Neuronal Pathways Activated Following Environmental Enrichment by Resting State Functional Magnetic Resonance Imaging

Abstract

We have shown that experience of transgenic mice harboring familial Alzheimer’s disease (FAD)-linked AβPPswe/PS1ΔE9 in an enriched environment enhances hippocampal neurogenesis and synaptic plasticity and attenuates neuropathology. Nevertheless, the neuronal pathways activated following environmental enrichment underlying this effect are unknown. Using resting-state functional magnetic resonance imaging, we present preliminary evidence to show that transgenic mice, which had been housed in an enriched environment, show increased connectivity between CA1 and cortical areas compared to mice from standard housing. This is the first preliminary demonstration of live-activated neuronal pathways following environmental enrichment in FAD mice. Understanding the activated pathways may unravel the molecular mechanism underlying environmental enrichment-enhanced neuroplasticity in FAD.

Large-scale topology and the default mode network in the mouse connectome

“…As hypothesized, structural connectivity can predict functional connectivity in the mouse, a result similar to that observed on a smaller scale in humans and macaques (32-34, 41, 53-55). We note that other studies have looked at rodent functional connectivity data using rs-fcMRI with limited success (16,19,21,22,56,57). Others have used optical intrinsic signal technique (23), which is limited to surface views of the cortex with an inability to probe deep brain structures.…”

“…Advances in rs-fcMRI and its computational evaluation have begun to shed some light on homology between brain networks in primates (14); however, there is a paucity of studies comparing primates with rodents. Despite evidence for intrinsic functional connectivity in rats (15)(16)(17)(18)(19) and to a lesser extent, mice (20)(21)(22)(23)(24), comparing large-scale network organization between mice and primates has proven difficult.…”

Neuroplasticity and MRI: A perfect match

“…Other studies in humans used MRS to deduce metabolic changes resulting from endurance-training in middle-aged subjects (Gonzales, Tarumi et al 2013), fast GABA level alterations were observed in the sensorimotor cortex due to motor-learning preclinical research involving animal models can be translated to the human brain (Nithianantharajah andHannan 2006, Svensson, Lexell et al 2014). A particularly interesting preclinical example can be found in a (preliminary) study by Little et al (2012). Based on rsfMRI measures, they found an increased functional connectivity between CA1 and cortical areas when housing transgenic mice in environmental enriched conditions (Little, Foxely et al 2012).…”

Changes in Structural and Functional Plasticity of the Brain Induced by Environmental Enrichment

“…[61] наблюдали, что у стареющих APP-трансгенных животных, подвергнутых воздействию ОС, отмечались когнитивные улучшения в простран-ственном обучении, но при этом исследователи не реги-стрировали никаких изменений в отложении β-амилоида по сравнению с животными, содержащимися в стандарт-ных условиях. Хотя в данном исследовании использовали небольшое число животных, и улучшение когнитивных функций было умеренным, существуют доказательства того, что увеличение количества упражнений может при-вести к усилению когнитивных функций [62], что находит свое отражение в структурно-функциональных особен-ностях формирования гиппокампально-корковых взаи-модействий [63].…”

“…Морфологические, функциональные и биохимиче-ские параметры, характеризующие действие ОС на ЦНС, многообразны и пока должным образом не систематизи-рованы [20,21,27,63]. Идентификация молекулярных и клеточных эффектов многостимульной среды может не только обеспечить формирование новых представлений о влиянии окружающей среды на патогенез заболеваний головного мозга, но и создать платформу для разработки терапевтических агентов, которые имитируют или усили-вают полезные эффекты среды.…”