Imaging and spectroscopic methods to investigate adult neurogenesis in vivo: New models and new avenues

Abstract

Adult neurogenesis (AN) can be defined as the birth and development of new neurons in adulthood. Until the 1990s, AN was deemed not to happen after birth. Gradually, several groups demonstrated that specific zones of the brain of various species had a neurogenic potential. AN could be the key to treating a large range of neurodegenerative, neuropsychiatric, and metabolic diseases, with a better understanding of the mechanisms allowing for regeneration of new neurons. Despite this promising prospect, the existence of AN has not been validated in vivo in humans and therefore remains controversial. Moreover, the weight of AN-induced plasticity against other mechanisms of brain plasticity is not known, adding to the controversy. In this review, we would like to show that recent technical advances in brain MR imaging methods combined with improved models can resolve the debate.

Keywords: MRI; MRS; adult neurogenesis; animal models; controversy; diffusion; human brain.

Figure 1

Adult neurogenesis in the hypothalamus of sheep. (A) Different stages of adult neurogenesis from neural stem cells (NSCs) to DX-positive mature neurons. (B) Photomicrograph of DCX-positive staining in the arcuate nucleus of the sheep hypothalamus. (C,D) Drawings showing variations in DCX + staining during photoperiod.

Figure 2

Patchwork of different MR techniques used to explore the response of different structural and functional MR parameters to AN in the sheep hypothalamus during photopriodism. (A) Structural MR imaging and sensitivity to AN in the sheep hypothalamus. (B) VBM analysis conducted from the segmentation of MPRAGE images (0.5 × 0.5 × 0.2 mm³). (C) Labeled fiber staining from the Sheep Brain Atlas (Michigan State University) showing the hypothalamus of the sheep with specific nuclei such as the arcuate nucleus. (D) VBM analysis detected significant structural changes occurring during the short days of the year (SP, short period) during AN compared to the long days of the year (LP, long period). (E) Functional MR imaging and sensitivity to AN rCBVmaps. (F) Comparison between LP and SP in the hypothalamus show a significant increase during SP (see Just et al., for methods). (G) Example of vascular occupancy (VASO) map during C02 inhalation. (H) BOLD fMRI upon hypercapnic challenge during SP (Chevillard et al., 2021). (I) ¹H-MRS of the hypothalamus demonstrated activation in hypothalamic areas and corresponded well to changes in glutamate. (J) Example of Myelin water fraction (MWf) and T2 maps. These examples were extracted from data, which are still under analysis but appear to show some consistent response among all the different MR modalities used with structural, functional, and hemodynamic changes occurring during the period of AN.