Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induce...Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective.We conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for intervention.Then,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was investigated.In addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational potential.The results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all P<0.001).In contrast,the volume of the hippocampus did not show significant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both P<0.001).Subsequently,rTMS was applied to the occipital cortex,which is anatomically connected to the hippocampus,in the MAM models during adolescence.The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(P<0.01),while the volume of the striatum remained unchanged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(P<0.01),and these volumetric changes were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for earlyonset mental disorders with neuro展开更多
Precise and reliable presentation of odorants to animals is crucial for olfactory studies.Although odor stimulation systems in anesthetized or awake,head-fixed animals are well established,temporally precise odor prese...Precise and reliable presentation of odorants to animals is crucial for olfactory studies.Although odor stimulation systems in anesthetized or awake,head-fixed animals are well established,temporally precise odor presentation in awake,freely moving animals remains a challenge.Here,we describe a new odor stimulation system which presents odors directly to the nostrils of freely moving mice.The system comprises 3 modules:an odor-delivery module,an odor-generation module,and a control module.The new system is precise and temporally reliable,and odor stimulation can be triggered by specific sniffing phases or other events.Moreover,the system can be combined with neural recordings,such as electrophysiology,and olfactory behavioral tests to investigate how neurons in the brain represent odor information during individual olfactory behaviors.This innovative odor stimulation system may replace traditional stimulation systems:It will enable precise odor presentation in a wide range of olfactory studies in freely moving animals.展开更多
基金supported by the National Science Fund for Distinguished Young Scholars(81725005)the National Natural Science Foundation Regional Innovation and Development Joint Fund(U20A6005)+5 种基金the National Natural Science Foundation of China(82151315 and 62176129)the National Key Research and Development Program(2022YFC2405605)the Jiangsu Provincial Key Research and Development Program(BE2021617 and BE2022160)the Key Project supported by Medical Science and Technology Development Foundation,Jiangsu Commission of Health(ZD2021026)the Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB818)the Postdoctoral Research Project of Changzhou Medical Center,Nanjing Medical University(CMCP202305).
文摘Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective.We conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for intervention.Then,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was investigated.In addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational potential.The results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all P<0.001).In contrast,the volume of the hippocampus did not show significant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both P<0.001).Subsequently,rTMS was applied to the occipital cortex,which is anatomically connected to the hippocampus,in the MAM models during adolescence.The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(P<0.01),while the volume of the striatum remained unchanged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(P<0.01),and these volumetric changes were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for earlyonset mental disorders with neuro
基金supported by the National Natural Science Foundation of China(NSFC,31872771 and 32070995 to Anan Li,31872770 to Yufeng Shao)the Jiangsu Province Innovative and Entrepreneurial Team Program.
文摘Precise and reliable presentation of odorants to animals is crucial for olfactory studies.Although odor stimulation systems in anesthetized or awake,head-fixed animals are well established,temporally precise odor presentation in awake,freely moving animals remains a challenge.Here,we describe a new odor stimulation system which presents odors directly to the nostrils of freely moving mice.The system comprises 3 modules:an odor-delivery module,an odor-generation module,and a control module.The new system is precise and temporally reliable,and odor stimulation can be triggered by specific sniffing phases or other events.Moreover,the system can be combined with neural recordings,such as electrophysiology,and olfactory behavioral tests to investigate how neurons in the brain represent odor information during individual olfactory behaviors.This innovative odor stimulation system may replace traditional stimulation systems:It will enable precise odor presentation in a wide range of olfactory studies in freely moving animals.
