Systemic regulation of adult neural stem cells: investigating the role of peripheral signals in adult neurogenesis

Adult neurogenesis, the process by which Neural Stem Cells (NSCs) generate new neurons in the mature brain, is increasingly recognized as a dynamic phenomenon regulated by systemic signals.

Physiological states such as exercise, stress, aging, and metabolic changes modulate adult neurogenesis by altering systemic hormones, immune signals, and growth factors that shape the neurogenic niche. Thus, alterations in physiology are translated into local molecular signals that modulate the microenvironment of NSCs and affect their activation as well as the generation, survival, and integration of newly formed neurons into the pre-existing circuitry.

Furthermore, in many diseases—including depression, neurodegenerative disorders, and chronic inflammation—disruptions in these systemic signals lead to reduced proliferation, impaired maturation, or diminished survival of new hippocampal neurons, linking whole-body physiology to brain plasticity and cognitive function.

Notably, the behaviour of NSCs within the brain’s proliferative niches (mainly the hippocampus and the anterior subventricular zone) is strongly associated with regional identities established during embryonic development. These developmental origins endow NSC populations with different responsiveness to niche-derived cues and distinct capacities for self-renewal or differentiation. As a result, NSCs in different neurogenic areas are differentially regulated by local microenvironmental factors such as extracellular matrix composition, vascular signals, neurotransmitters, and inflammatory mediators. Recent evidence suggests that diverse external stimuli can selectively activate subsets of NSCs, but the precise mechanisms by which these heterogeneous NSCs integrate positional information with external cues are poorly understood.

These findings emphasize that adult neurogenesis is a highly dynamic process that integrates peripheral and systemic cues—linking body physiology to the generation of new neurons and thereby shaping brain plasticity and resilience. Elucidating the bidirectional communication between the periphery and adult NSCs may uncover novel therapeutic strategies for behaviour-related disorders.

This Research Topic aims to dissect how alterations in body physiology affect the behaviour of adult NSCs in the brain, linking whole-body states to brain plasticity and cognitive function. The objective is to unify existing evidence to increase our understanding of the biological significance of adult neurogenesis and its role in linking the immune, hormonal, and metabolic systems to the brain.

To this end, the collection will explore the cellular and molecular pathways through which adult NSCs are affected by neuroimmune interactions, hormones, metabolites, and other components of the neurogenic microenvironment, focusing on factors that are modulated by environmental cues and physiological state alterations such as social and cognitive enrichment, stress, depression, neurodegenerative disorders, and chronic inflammation.

It will also investigate how genetic background and prenatal exposure to specific stimuli interact to shape the biological characteristics of adult NSCs and their ability to sense physiological systemic alterations.
Finally, it will examine how the specific brain location of adult NSCs influences their responsiveness to molecular signals driven by physiological or pathological states.

We particularly welcome articles on the following sub-topics:

1. Cellular and molecular microenvironmental components affecting adult neurogenesis:
• Hormones, neuropeptides, metabolites, other factors
• Role of microglia and astrocytes
• Role of neurons, blood vessels, ependymal cells

2. Genetic and developmental factors:
• Genes that influence adult NSC behaviour
• Gene–environment interactions
• Impact of developmental cues and early-life experiences on adult NSCs

3. Disease and adult neurogenesis:
• Stress, depression
• Chronic inflammation
• Neurodegeneration
• Psychiatric diseases


We acknowledge the initiation and support of this Research Topic by the Mediterranean Neuroscience Society (MNS). We hereby state publicly that the MNS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the MNS.

Keywords: neural stem cells, adult neurogenesis, pathological, behavior disorder, cognition, plasticity, resilience, PNS, inflammation, Society Affiliation RT

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