Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions

Abstract

There is growing evidence that both peripheral and resident immune cells play an important part in regulating adult neural stem cell proliferation and neurogenesis, although the contribution of the various immune cell types is still unclear. Mast cells, a population of immune cells known for their role in the allergic response, have been implicated in the regulation of adult hippocampal neurogenesis. Mast cell-deficient c-kitW-sh/W-sh mice have previously been shown to exhibit significantly decreased adult hippocampal neurogenesis and associated learning and memory deficits. However, given that numerous other cell types also express high levels of c-kit, the utility of these mice as a reliable model of mast cell-specific depletion is questionable. We show here, using a different model of mast cell deficiency (Mcpt5CreR26DTA/DTA), that precursor proliferation and adult neurogenesis are not influenced by mast cells in vivo. Interestingly, when applied at supraphysiological doses, mast cells can activate latent hippocampal precursor cells and increase subventricular zone precursor proliferation in vitro, an effect that can be blocked with specific histamine-receptor antagonists. Thus, we conclude that while both mast cells and their major chemical mediator histamine have the potential to affect neural precursor proliferation and neurogenesis, this is unlikely to occur under physiological conditions.

Mouse models of immune dysfunction: Their neuroanatomical differences reflect their anxiety-behavioural phenotype

“…Our analysis also showed no significantly altered neuroanatomy in the dorsal hippocampus of Rag1 mutants. We found thalamic changes in mast cell-deficient Kit mutants, which is consistent with mast cells migrating along blood vessels of the hippocampus and fimbria during postnatal development and penetrating into the thalamus, where they remain throughout adulthood [50].…”

Histamine modulates hippocampal inflammation and neurogenesis in adult mice

“…Another important process regulated by histamine is adult neurogenesis, which occurs constitutively throughout life, mainly in the subventricular zone (SVZ) and in the hippocampal subgranular zone (SGZ). In vitro studies showed that H1R, H2R and H3R are expressed in neural stem cell (NSC) niches and that histamine induces NSC proliferation and neuronal differentiation through H2R and H1R signaling pathways, respectively 3,11–13 . In fact, histamine activation of H1R results in SVZ NSC differentiation via Mash1, DLX2 and Ngn1 into mature neurons, enabling the integration and differentiation of SVZ progenitors when grafted onto hippocampal slices or in the mouse hippocampus and striatum in vivo 3 .…”

Mouse models of immune dysfunction: their neuroanatomical differences reflect their anxiety-behavioural phenotype

“…For example, we did not find altered morphology of the dorsal hippocampus in Rag1 mutants, which is consistent with histology studies [ 51 ]. We found thalamic changes in mast cell-deficient Kit mutants, consistent with mast cell migration into the thalamus during development [ 52 ]. Phenotypes also showed some degree of lateralisation that has previously been seen in autism models [ 53 , 54 ].…”