Unfortunately,ag ing is not a reversible phenomenon and the processes of senescence are unavoidable.However,the biological effects of aging may be turned back,and with those,it can be reduced risk of all age-related i...Unfortunately,ag ing is not a reversible phenomenon and the processes of senescence are unavoidable.However,the biological effects of aging may be turned back,and with those,it can be reduced risk of all age-related illnesses,such as cardiovascular diseases,cancer,diabetes,and neurodegenerative diseases,including Alzheimer’s disease(AD),and Parkinson’s diseases(PD).In the latest decades,scientists worldwide therefore have developed several strategies,either natural or pharmacological,to counteract aging phenomena,with the final goal to improve human life expectancy.The main scientific rationale beyond these strategies focuses on the opportunity to reduce chronic low-grade inflammation(inflammaging),the increase in oxidative stress damage,and the impairment in the immune system,all typical mechanisms of senescence(Verdaguer et al.,2012).展开更多
Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision,cognition), it is important to examine the individual contributions of these factors with ARVL. While therelationship...Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision,cognition), it is important to examine the individual contributions of these factors with ARVL. While therelationship between the vestibular and visual systems has been well studied (Bronstein et al., 2015),little is known about the association of the peripheral vestibular system with neurodegenerative disorders (Cronin et al., 2017). Further, emerging research developments implicate the vestibular system asan opportunity for examining brain function beyond balance, and into other areas, such as cognition andpsychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide thedevelopment of integrated interventions for patients who remain at risk for decline. In this review, wewill discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relatesto neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, withan emphasis on improving care for patients with ARVL.展开更多
Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ exc...Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ excitability＂ of glia. In mammalian glial cells the major source of Ca^2＋ for this excitability is the lumen of the endoplasmic reticulum （ER）, which is ultimately （re）filled from the extracellular space. This occurs via store-operated Ca^2＋ entry （SOCE） which is supported by a specific signaling system connecting the ER with plasmalemmal Ca^2＋ entry. Here, emptying of the ER Ca^2＋ store is necessary and sufficient for the activation of SOCE, and without Ca^2＋ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca^2＋ sensors, such as stromal interaction molecule, and possibly ER Ca^2＋ pumps （of the SERCA type）. There are at least two sets of plasmalemmal channels mediating SOCE, the Ca2＊-release activated channels, Orai, and transient receptor potential （TRP） channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SOCE. In physiological conditions the SOCE pathway is instrumental for the sustained phase of the Ca^2＋ signal observed following stimulation of metabotropic receptors on glial cells.展开更多
Background:It remains unknow whether retinal tissue perfusion occurs in patients with Alzheimer’s disease.The goal was to determine retinal tissue perfusion in patients with clinical Alzheimer’s disease(CAD).Methods...Background:It remains unknow whether retinal tissue perfusion occurs in patients with Alzheimer’s disease.The goal was to determine retinal tissue perfusion in patients with clinical Alzheimer’s disease(CAD).Methods:Twenty-four CAD patients and 19 cognitively normal(CN)age-matched controls were recruited.A retinal function imager(RFI,Optical Imaging Ltd.,Rehovot,Israel)was used to measure the retinal blood flow supplying the macular area of a diameter of 2.5 mm centered on the fovea.Blood flow volumes of arterioles(entering the macular region)and venules(exiting the macular region)of the supplied area were calculated.Macular blood flow was calculated as the average of arteriolar and venular flow volumes.Custom ultra-high-resolution optical coherence tomography(UHR–OCT)was used to calculate macular tissue volume.Automated segmentation software(Orion,Voxeleron LLC,Pleasanton,CA)was used to segment six intra-retinal layers in the 2.5 mm(diameter)area centered on the fovea.The inner retina(containing vessel network),including retinal nerve fiber layer(RNFL),ganglion cell-inner plexiform layer(GCIPL),inner nuclear layer(INL)and outer plexiform layer(OPL),was segmented and tissue volume was calculated.Perfusion was calculated as the flow divided by the tissue volume.Results:The tissue perfusion in CAD patients was 2.58±0.79 nl/s/mm^(3)(mean±standard deviation)and was significantly lower than in CN subjects(3.62±0.44 nl/s/mm^(3),P<0.01),reflecting a decrease of 29%.The flow volume was 2.82±0.92 nl/s in CAD patients,which was 31%lower than in CN subjects(4.09±0.46 nl/s,P<0.01).GCIPL tissue volume was 0.47±0.04 mm^(3) in CAD patients and 6%lower than CN subjects(0.50±0.05 mm^(3),P<0.05).No other significant alterations were found in the intra-retinal layers between CAD and CN participants.Conclusions:This study is the first to show decreased retinal tissue perfusion that may be indicative of diminished tissue metabolic activity in patients with clinical Alzheimer’s disease.展开更多
基金supported in part by The Evelyn F.McKnight Brain Institute.
文摘Unfortunately,ag ing is not a reversible phenomenon and the processes of senescence are unavoidable.However,the biological effects of aging may be turned back,and with those,it can be reduced risk of all age-related illnesses,such as cardiovascular diseases,cancer,diabetes,and neurodegenerative diseases,including Alzheimer’s disease(AD),and Parkinson’s diseases(PD).In the latest decades,scientists worldwide therefore have developed several strategies,either natural or pharmacological,to counteract aging phenomena,with the final goal to improve human life expectancy.The main scientific rationale beyond these strategies focuses on the opportunity to reduce chronic low-grade inflammation(inflammaging),the increase in oxidative stress damage,and the impairment in the immune system,all typical mechanisms of senescence(Verdaguer et al.,2012).
文摘Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision,cognition), it is important to examine the individual contributions of these factors with ARVL. While therelationship between the vestibular and visual systems has been well studied (Bronstein et al., 2015),little is known about the association of the peripheral vestibular system with neurodegenerative disorders (Cronin et al., 2017). Further, emerging research developments implicate the vestibular system asan opportunity for examining brain function beyond balance, and into other areas, such as cognition andpsychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide thedevelopment of integrated interventions for patients who remain at risk for decline. In this review, wewill discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relatesto neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, withan emphasis on improving care for patients with ARVL.
基金supported by an Alzheimer’s Research Trust(UK)Programme Grant(ART/PG2004A/1)to A.V.by a National Science Foundation grant(CBET 0943343)to V.P
文摘Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ excitability＂ of glia. In mammalian glial cells the major source of Ca^2＋ for this excitability is the lumen of the endoplasmic reticulum （ER）, which is ultimately （re）filled from the extracellular space. This occurs via store-operated Ca^2＋ entry （SOCE） which is supported by a specific signaling system connecting the ER with plasmalemmal Ca^2＋ entry. Here, emptying of the ER Ca^2＋ store is necessary and sufficient for the activation of SOCE, and without Ca^2＋ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca^2＋ sensors, such as stromal interaction molecule, and possibly ER Ca^2＋ pumps （of the SERCA type）. There are at least two sets of plasmalemmal channels mediating SOCE, the Ca2＊-release activated channels, Orai, and transient receptor potential （TRP） channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SOCE. In physiological conditions the SOCE pathway is instrumental for the sustained phase of the Ca^2＋ signal observed following stimulation of metabotropic receptors on glial cells.
基金supported by the McKnight Brain Institute,NIH Center Grant P30 EY014801,UM Dean's NIH Bridge Award(UM DBA 2019-3)a grant from Research to Prevent Blindness(RPB)and the North American Neuroophthalmology Society.
文摘Background:It remains unknow whether retinal tissue perfusion occurs in patients with Alzheimer’s disease.The goal was to determine retinal tissue perfusion in patients with clinical Alzheimer’s disease(CAD).Methods:Twenty-four CAD patients and 19 cognitively normal(CN)age-matched controls were recruited.A retinal function imager(RFI,Optical Imaging Ltd.,Rehovot,Israel)was used to measure the retinal blood flow supplying the macular area of a diameter of 2.5 mm centered on the fovea.Blood flow volumes of arterioles(entering the macular region)and venules(exiting the macular region)of the supplied area were calculated.Macular blood flow was calculated as the average of arteriolar and venular flow volumes.Custom ultra-high-resolution optical coherence tomography(UHR–OCT)was used to calculate macular tissue volume.Automated segmentation software(Orion,Voxeleron LLC,Pleasanton,CA)was used to segment six intra-retinal layers in the 2.5 mm(diameter)area centered on the fovea.The inner retina(containing vessel network),including retinal nerve fiber layer(RNFL),ganglion cell-inner plexiform layer(GCIPL),inner nuclear layer(INL)and outer plexiform layer(OPL),was segmented and tissue volume was calculated.Perfusion was calculated as the flow divided by the tissue volume.Results:The tissue perfusion in CAD patients was 2.58±0.79 nl/s/mm^(3)(mean±standard deviation)and was significantly lower than in CN subjects(3.62±0.44 nl/s/mm^(3),P<0.01),reflecting a decrease of 29%.The flow volume was 2.82±0.92 nl/s in CAD patients,which was 31%lower than in CN subjects(4.09±0.46 nl/s,P<0.01).GCIPL tissue volume was 0.47±0.04 mm^(3) in CAD patients and 6%lower than CN subjects(0.50±0.05 mm^(3),P<0.05).No other significant alterations were found in the intra-retinal layers between CAD and CN participants.Conclusions:This study is the first to show decreased retinal tissue perfusion that may be indicative of diminished tissue metabolic activity in patients with clinical Alzheimer’s disease.
