An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus

Abstract

With continued debate over the functional significance of adult neurogenesis, identifying an in vivo correlate of neurogenesis has become an important goal. Here we rely on the coupling between neurogenesis and angiogenesis and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis. First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice. Among all hippocampal subregions, exercise was found to have a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis. Moreover, exercise-induced increases in dentate gyrus CBV were found to correlate with postmortem measurements of neurogenesis. Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans. As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function. Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis and that exercise differentially targets the dentate gyrus, a hippocampal subregion important for memory and implicated in cognitive aging.hippocampus ͉ in vivo imaging ͉ cerebral blood volume ͉ angiogenesis T he hippocampal formation, a brain circuit made up of separate but interconnected subregions (1), is vital for memory function (2) and is targeted by the aging process (3). The dentate gyrus is the only hippocampal subregion that supports neurogenesis in the adult brain (4-6). Nevertheless, because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined. With this limitation in mind, we have explored different imaging approaches applicable to rodents and humans that might provide an in vivo correlate of neurogenesis.Although imaging radioligands designed to bind newly dividing cells is an attractive approach, positron emission tomography imaging suffers inherently poor resolution and cannot visualize the dentate gyrus. Additionally, radiolabeling newborn cells introduces potential safety concerns. For these reasons, we have focused on MRI technologies instead. Notably, a coupling has been established between neurogenesis and angiogenesis (7,8). The process of angiogenesis, in turn, gradually gives rise to the formation of new blood vessels, increasing regional microvascular density (9-12). Importantly, vascular density can be measured in vivo with imaging techniques that map regional blood volume. Numerous studies have established a tight relationship between angiogenesis and regional blood volume (13-17), including in the brain where regional angiogenesis is coupled to regional cerebral blood volume (CBV) (18)(19)(20)(21)(22)(23)(24)(25)(26).Because CBV can be measured with MRI, we hypothesized that a regionally selective increase in hippocampal CBV might provide an imaging correlate of neurogenesis. This hypothesis was tested in...

Running enhances spatial pattern separation in mice

“…Research pertaining to the underlying mechanisms has revealed significant central physiological and structural changes resulting from exercise. In particular, in the hippocampus, a brain region important for learning and memory, running increases neurotrophin gene expression (8,9), vascularization (10,11), dendritic spine density (12,13), and synaptic plasticity (6,9). These exercise-induced changes are associated with a robust increase in dentate gyrus neurogenesis in young rodents as well as a reversal of the agingrelated decline in cell genesis (6,7,10,14).…”

Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis

“…Higher physical activity level seems to be able to increase gray and white matter volume in the prefrontal cortex (Colcombe et al, 2006) and is associated with greater sparing of prefrontal and temporal brain regions (Erickson et al, 2010). Moreover, exercise training increases cerebral blood volume (Burdette et al, 2010) and perfusion of the hippocampus (Pereira et al, 2007), one of the most important organ in the control of food intake. If these anatomical changes correspond to better cognitive function is, however, not fully understood.…”

Putative Neuroprotective and Neurotoxic Kynurenine Pathway Metabolites Are Associated with Hippocampal and Amygdalar Volumes in Subjects with Major Depressive Disorder

“…Major depressive disorder (MDD) has been associated with reductions in hippocampal and amygdalar volume that are thought to reflect dendritic atrophy occurring in the context of excitotoxicity, decreased neurogenesis, and impaired neurotrophic function (Koolschijn et al, 2009;Pereira et al, 2007;Petrik et al, 2012;Savitz and Drevets, 2009;Stockmeier et al, 2004). At least a subgroup of individuals with MDD also display putative signs of inflammation such as elevated circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1b (IL-1b) (Dowlati et al, 2010;Howren et al, 2009).…”