Neurogenic-dependent changes in hippocampal circuitry underlie the procognitive effect of exercise in aging mice

Zhou, Xiaoqing; Blackmore, Daniel G.; Zhuo, Junjie; Nasrallah, Fatima A.; To, Xuan Vinh; Kurniawan, Nyoman D.; Carlisle, Alison; Vien, King-Year; Chuang, Kai‐Hsiang; Jiang, Tianzi; Bartlett, Perry F.

doi:10.1016/j.isci.2021.103450

Cited by 10 publications

(8 citation statements)

References 75 publications

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“…Given previous findings relating neuron density, MD, and ISOVF to cognitive abilities, one may expect B6 mice in our cohort to have poor memory performance. In mice, higher neuron density in the BLA is associated with improved CFM performance ( Yang et al, 2008 ), and neurogenesis-driven decreases in MD track spatial learning improvements during a related active place avoidance paradigm ( Zhou et al, 2021 ). Additionally, higher cortical neuron counts in mice have been associated with better perceptual discrimination ( Fang and Yuste, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

Murdy

Dunn

Singh

et al. 2023

Front. Behav. Neurosci.

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In human Alzheimer’s disease (AD) patients and AD mouse models, both differential pre-disease brain features and differential disease-associated memory decline are observed, suggesting that certain neurological features may protect against AD-related cognitive decline. The combination of these features is known as brain reserve, and understanding the genetic underpinnings of brain reserve may advance AD treatment in genetically diverse human populations. One potential source of brain reserve is brain microstructure, which is genetically influenced and can be measured with diffusion MRI (dMRI). To investigate variation of dMRI metrics in pre-disease-onset, genetically diverse AD mouse models, we utilized a population of genetically distinct AD mice produced by crossing the 5XFAD transgenic mouse model of AD to 3 inbred strains (C57BL/6J, DBA/2J, FVB/NJ) and two wild-derived strains (CAST/EiJ, WSB/EiJ). At 3 months of age, these mice underwent diffusion magnetic resonance imaging (dMRI) to probe neural microanatomy in 83 regions of interest (ROIs). At 5 months of age, these mice underwent contextual fear conditioning (CFC). Strain had a significant effect on dMRI measures in most ROIs tested, while far fewer effects of sex, sex*strain interactions, or strain*sex*5XFAD genotype interactions were observed. A main effect of 5XFAD genotype was observed in only 1 ROI, suggesting that the 5XFAD transgene does not strongly disrupt neural development or microstructure of mice in early adulthood. Strain also explained the most variance in mouse baseline motor activity and long-term fear memory. Additionally, significant effects of sex and strain*sex interaction were observed on baseline motor activity, and significant strain*sex and sex*5XFAD genotype interactions were observed on long-term memory. We are the first to study the genetic influences of brain microanatomy in genetically diverse AD mice. Thus, we demonstrated that strain is the primary factor influencing brain microstructure in young adult AD mice and that neural development and early adult microstructure are not strongly altered by the 5XFAD transgene. We also demonstrated that strain, sex, and 5XFAD genotype interact to influence memory in genetically diverse adult mice. Our results support the usefulness of the 5XFAD mouse model and convey strong relationships between natural genetic variation, brain microstructure, and memory.

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Section: Discussionmentioning

confidence: 99%

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

Murdy

Dunn

Singh

et al. 2023

Front. Behav. Neurosci.

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“…As yet, no study probed the effects of exogenous EST on rsFC in men. There is some evidence that changes in rsFC of the hippocampus depend on hippocampal neurogenesis in female mice 76 . However, previous studies 77 , 78 on hippocampal neurogenesis did not detect significant EST effects in male rats, either, and suggest an androgen-dependent mechanism, but it is unclear whether and how altered neurogenesis translates to altered rsFC in humans.…”

Section: Discussionmentioning

confidence: 99%

Effects of exogenous oxytocin and estradiol on resting-state functional connectivity in women and men

Coenjaerts

Adrovic

Trimborn

et al. 2023

Sci Rep

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Possible interactions of the neuropeptide oxytocin and the sex hormone estradiol may contribute to previously observed sex-specific effects of oxytocin on resting-state functional connectivity (rsFC) of the amygdala and hippocampus. Therefore, we used a placebo-controlled, randomized, parallel-group functional magnetic resonance imaging study design and measured amygdala and hippocampus rsFC in healthy men (n = 116) and free-cycling women (n = 111), who received estradiol gel (2 mg) or placebo before the intranasal administration of oxytocin (24 IU) or placebo. Our results reveal significant interaction effects of sex and treatments on rsFC of the amygdala and hippocampus in a seed-to-voxel analysis. In men, both oxytocin and estradiol significantly decreased rsFC between the left amygdala and the right and left lingual gyrus, the right calcarine fissure, and the right superior parietal gyrus compared to placebo, while the combined treatment produced a significant increase in rsFC. In women, the single treatments significantly increased the rsFC between the right hippocampus and the left anterior cingulate gyrus, whereas the combined treatment had the opposite effect. Collectively, our study indicates that exogenous oxytocin and estradiol have different region-specific effects on rsFC in women and men and that the combined treatment may produce antagonistic effects.

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“…Moreover, the improvement in hippocampal-based learning in aged mice after physical exercise is dependent on neurogenesis in the dentate gyrus and is regulated by growth hormone level changes. Specific changes in hippocampal circuitry underlying the cognitive improvements resulting from physical activity were also identified, suggesting dependency on neurogenesis activation in aged animals (Blackmore et al, 2021;Zhou et al, 2021). Cheng et al (2020) observed that treadmill exercise promotes neurogenesis and myelin repair by upregulating the Wnt/β-catenin signaling pathway and improves the neurological deficit caused by focal cerebral ischemia/ reperfusion.…”

Section: Promotion Of Neurogenesismentioning

confidence: 97%

Insight Into the Mechanism of Exercise Preconditioning in Ischemic Stroke

Zhu¹,

Sun²,

Hu³

et al. 2022

Front. Pharmacol.

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Exercise preconditioning has attracted extensive attention to induce endogenous neuroprotection and has become the hotspot in neurotherapy. The training exercise is given multiple times before cerebral ischemia, effectively inducing ischemic tolerance and alleviating secondary brain damage post-stroke. Compared with other preconditioning methods, the main advantages of exercise include easy clinical operation and being readily accepted by patients. However, the specific mechanism behind exercise preconditioning to ameliorate brain injury is complex. It involves multi-pathway and multi-target regulation, including regulation of inflammatory response, oxidative stress, apoptosis inhibition, and neurogenesis promotion. The current review summarizes the recent studies on the mechanism of neuroprotection induced by exercise, providing the theoretical basis of applying exercise therapy to prevent and treat ischemic stroke. In addition, we highlight the various limitations and future challenges of translational medicine from fundamental study to clinical application.

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Neurogenic-dependent changes in hippocampal circuitry underlie the procognitive effect of exercise in aging mice

Cited by 10 publications

References 75 publications

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

Effects of exogenous oxytocin and estradiol on resting-state functional connectivity in women and men

Insight Into the Mechanism of Exercise Preconditioning in Ischemic Stroke

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