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Updated: May 6, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia-mediated neurogenesis is linked to cognitive deficits in a two-hit model of maternal immune activation and
Qiuying Zhao1, Jiutai Wang1, Yue Han1
1Center of Psychosomatic Medicine, Sichuan Provincial People's Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Abstract:
Maternal immune activation (MIA), combined with exposure to a second environmental stressor, contributes to neurodevelopmental disorders in offspring. Immune-challenged microglial cells play a crucial role in the pathogenesis of these disorders. However, the mechanisms through which microglia mediate cognitive impairments in individuals exposed to dual stresses remain poorly understood. In this research, pregnant rat dams were subjected to viral mimetic, poly(I:C), and their young male offspring were either exposed to a second stressor or not during juvenile age. The results showed that a pathological microglial phenotype was accompanied by impairments in hippocampal neurogenesis and deficits in hippocampus-dependent spatial learning and memory in the MIA offspring exposed to the second stressor during juvenile age. Minocycline shifts pathological microglial cells to a neuroprotective state, alleviating neurogenesis impairments and spatial learning and memory deficits in these "two-hit" animals. However, the cognitive improvements induced by minocycline were blocked by temozolomide treatment, as evidenced by the inhibition of neurogenesis. Our findings highlight the important role of hippocampal neurogenesis in inflammatory-mediated cognitive abnormalities and provide insights into the roles of microglia underlying neurodevelopmental disorders.
Insights
Maternal immune activation combined with a second stressor impairs offspring cognition by affecting brain cells called microglia. Treating these animals with minocycline improved memory, but this effect was blocked by temozolomide.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Maternal immune activation (MIA) and subsequent environmental stressors contribute to neurodevelopmental disorders.
- Microglia, the brain's immune cells, are implicated in the cognitive deficits seen in offspring exposed to dual stressors.
- The precise mechanisms by which microglia mediate cognitive impairments under these conditions are not fully understood.
Purpose of the Study:
- To investigate the role of microglia and hippocampal neurogenesis in cognitive impairments resulting from MIA and a second stressor.
- To evaluate the therapeutic potential of minocycline in mitigating these deficits.
- To explore the interplay between neurogenesis and microglial modulation in a "two-hit" model of neurodevelopmental disorders.
Main Methods:
- Pregnant rats were exposed to poly(I:C) (a viral mimetic) to induce MIA.
- Offspring were subjected to a second stressor during juvenile age.
- Hippocampal neurogenesis, spatial learning, and memory were assessed.
- The effects of minocycline and temozolomide on these parameters were evaluated.
Main Results:
- Dual-stress exposure led to pathological microglial activation, impaired hippocampal neurogenesis, and deficits in spatial learning and memory.
- Minocycline treatment shifted microglia to a neuroprotective state, improving neurogenesis and cognitive function.
- Temozolomide blocked minocycline's cognitive benefits by inhibiting neurogenesis.
Conclusions:
- Hippocampal neurogenesis is crucial for overcoming inflammatory-mediated cognitive abnormalities in offspring exposed to dual stressors.
- Microglial modulation offers a potential therapeutic strategy for neurodevelopmental disorders stemming from MIA and environmental insults.
- This study provides insights into the mechanisms underlying neurodevelopmental disorders and highlights the importance of neurogenesis in cognitive recovery.
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