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Central nervous system damage caused by traumatic injuries, iatrogenicity due to surgical interventions, stroke and neurodegenerative diseases is one of the most prevalent reasons for physical disability worldwide. During development, axons must elongate from the neuronal cell body to contact their precise target cell and establish functional connections. However, the capacity of the adult nervous system to restore its functionality after injury is limited. Given the inefficacy of the nervous system to heal and regenerate after damage, new therapies are under investigation to enhance axonal regeneration. Axon guidance cues and receptors, as well as the molecular machinery activated after nervous system damage, are organized into lipid raft microdomains, a term typically used to describe nanoscale membrane domains enriched in cholesterol and glycosphingolipids that act as signaling platforms for certain transmembrane proteins. Here, we systematically review the most recent findings that link the stability of lipid rafts and their composition with the capacity of axons to regenerate and rebuild functional neural circuits after damage. [ABSTRACT FROM AUTHOR]

Depression is characterized by the disruption of both neural circuitry and neurogenesis. Defects in hippocampal activity and volume, indicative of reduced neurogenesis, are associated with depression-related behaviors in both humans and animals. Neurogenesis in adulthood is considered an activity-dependent process; therefore, hippocampal neurogenesis defects in depression can be a result of defective neural circuitry activity. However, the mechanistic understanding of how defective neural circuitry can induce neurogenesis defects in depression remains unclear. This review highlights the current findings supporting the neural circuitry-regulated neurogenesis, especially focusing on hippocampal neurogenesis regulated by the entorhinal cortex, with regard to memory, pattern separation, and mood. Taken together, these findings may pave the way for future progress in neural circuitry–neurogenesis coupling studies of depression. [ABSTRACT FROM AUTHOR]

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth. [ABSTRACT FROM AUTHOR]