Current understanding and prospects for targeting neurogenesis in the treatment of cognitive impairment

Adult hippocampal neurogenesis is linked to memory formation in the adult brain, with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons. Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases. Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits. This review aims to expand the current understanding and prospects of targeting neurogenesis in the treatment of cognitive impairment. Recent research indicates the presence of abnormalities in AHN in several diseases associated with cognitive impairment, including cerebrovascular diseases, Alzheimer's disease, aging-related conditions, and issues related to anesthesia and surgery. The role of these abnormalities in the cognitive deficits caused by these diseases has been widely recognized, and targeting AHN is considered a promising approach for treating cognitive impairment. However, the underlying mechanisms of this role are not yet fully understood, and the effectiveness of targeting abnormal adult hippocampal neurogenesis for treatment remains limited, with a need for further development of treatment methods and detection techniques. By reviewing recent studies, we classify the potential mechanisms of adult hippocampal neurogenesis abnormalities into four categories: immunity, energy metabolism, aging, and pathological states. In immunity-related mechanisms, abnormalities in meningeal, brain, and peripheral immunity can disrupt normal adult hippocampal neurogenesis. Lipid metabolism and mitochondrial function disorders are significant energy metabolism factors that lead to abnormal adult hippocampal neurogenesis. During aging, the inflammatory state of the neurogenic niche and the expression of aging-related microRNAs contribute to reduced adult hippocampal neurogenesis and cognitive impairment in older adult patients. Pathological states of the body and emotional disorders may also result in abnormal adult hippocampal neurogenesis. Among the current strategies used to enhance this form of neurogenesis, physical therapies such as exercise, transcutaneous electrical nerve stimulation, and enriched environments have proven effective. Dietary interventions, including energy intake restriction and nutrient optimization, have shown efficacy in both basic research and clinical trials. However, drug treatments, such as antidepressants and stem cell therapy, are primarily reported in basic research, with limited clinical application. The relationship between abnormal adult hippocampal neurogenesis and cognitive impairment has garnered widespread attention, and targeting the former may be an important strategy for treating the latter. However, the mechanisms underlying abnormal adult hippocampal neurogenesis remain unclear, and treatments are lacking. This highlights the need for greater focus on translating research findings into clinical practice.