The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial ...The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial malfunctions in Alzheimer’s disease(AD).However,the underlying mechanisms remain to be elucidated.In this study,we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice,and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging(MRI)in patients on the AD spectrum.We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice.Moreover,MRI measurements of the PHG-OFC circuit had an accuracy of 77.33%for the classification of amnestic mild cognitive impairment converters versus non-converters.Thus,the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD,thereby providing a potential predictor for AD progression and a promising interventional approach for AD.展开更多
Our previous investigation suggested that faster seventh cervical nerve(C7)regeneration occurs in patients with cerebral injury undergoing contralateral C7 transfer.This finding needed further verification,and the mec...Our previous investigation suggested that faster seventh cervical nerve(C7)regeneration occurs in patients with cerebral injury undergoing contralateral C7 transfer.This finding needed further verification,and the mechanism remained largely unknown.Here,Tinel’s test revealed faster C7 regeneration in patients with cerebral injury,which was further confirmed in mice by electrophysiological recordings and histological analysis.Furthermore,we identified an altered systemic inflammatory response that led to the transformation of macrophage polarization as a mechanism underlying the increased nerve regeneration in patients with cerebral injury.In mice,we showed that,as a contributing factor,serum amyloid protein A1(SAA1)promoted C7 regeneration and interfered with macrophage polarization in vivo.Our results indicate that altered inflammation promotes the regenerative capacity of the C7 nerve by altering macrophage behavior.SAA1 may be a therapeutic target to improve the recovery of injured peripheral nerves.展开更多
基金Supported by the National Natural Science Foundation of China (81420108012,81671046,91832000,and 31700936)the Program of Excellent Talents in Medical Science of Jiangsu Province,China (JCRCA2016006)+4 种基金a Special Project of Clinical Medicine Science and Technology in Jiangsu Province,China (BL2014077)a Guangdong Province Grant (2017A030310496)Key-Area Research and Development Program of Guangdong Province,China (2018B030331001)a National Special Support Grant (W02020453)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017)。
文摘The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial malfunctions in Alzheimer’s disease(AD).However,the underlying mechanisms remain to be elucidated.In this study,we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice,and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging(MRI)in patients on the AD spectrum.We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice.Moreover,MRI measurements of the PHG-OFC circuit had an accuracy of 77.33%for the classification of amnestic mild cognitive impairment converters versus non-converters.Thus,the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD,thereby providing a potential predictor for AD progression and a promising interventional approach for AD.
基金This work was supported by the National Funds for Distinguished Young Scientists(81525009)the National Natural Science Foundation of China(81830063,81801363,and 81901419)+4 种基金the Priority Among Priorities of Shanghai Municipal Clinical Medicine Center(2017ZZ01006)the National Key R&D Program of China(2017YFC0840100 and 2017YFC0840106)the Technology Innovation Program of Shanghai Science and Technology Committee,China(18411950100)China Postdoctoral Science Foundation(2019M661369 and 2020T130110)a Research Project Funded by Shanghai Health and Family Planning Commission,China(20184Y0111 and 201640176).
文摘Our previous investigation suggested that faster seventh cervical nerve(C7)regeneration occurs in patients with cerebral injury undergoing contralateral C7 transfer.This finding needed further verification,and the mechanism remained largely unknown.Here,Tinel’s test revealed faster C7 regeneration in patients with cerebral injury,which was further confirmed in mice by electrophysiological recordings and histological analysis.Furthermore,we identified an altered systemic inflammatory response that led to the transformation of macrophage polarization as a mechanism underlying the increased nerve regeneration in patients with cerebral injury.In mice,we showed that,as a contributing factor,serum amyloid protein A1(SAA1)promoted C7 regeneration and interfered with macrophage polarization in vivo.Our results indicate that altered inflammation promotes the regenerative capacity of the C7 nerve by altering macrophage behavior.SAA1 may be a therapeutic target to improve the recovery of injured peripheral nerves.
