Neurobiology of Disease最新文献

{"title":"PTEN deletion in the adult dentate gyrus induces epilepsy","authors":"Jennifer M. Yonan ,&nbsp;Kevin D. Chen ,&nbsp;Tallie Z. Baram ,&nbsp;Oswald Steward","doi":"10.1016/j.nbd.2024.106736","DOIUrl":"10.1016/j.nbd.2024.106736","url":null,"abstract":"<div><div>Embryonic and early postnatal promotor-driven deletion of the phosphatase and tensin homolog (PTEN) gene results in neuronal hypertrophy, hyperexcitable circuitry and development of spontaneous seizures in adulthood. We previously documented that focal, vector-mediated PTEN deletion in mature granule cells of the adult dentate gyrus triggers dramatic growth of cell bodies, dendrites, and axons, similar to that seen with early postnatal PTEN deletion. Here, we assess the functional consequences of focal, adult PTEN deletion, focusing on its pro-epileptogenic potential. PTEN deletion was accomplished by injecting AAV-Cre either bilaterally or unilaterally into the dentate gyrus of double transgenic PTEN-floxed, ROSA-reporter mice. Hippocampal recording electrodes were implanted for continuous digital EEG with concurrent video recordings in the home cage. Electrographic seizures and epileptiform spikes were assessed manually by two investigators, and correlated with concurrent videos. Spontaneous electrographic and behavioral seizures appeared after focal PTEN deletion in adult dentate granule cells, commencing around 2 months post-AAV-Cre injection. Seizures occurred in the majority of mice with unilateral or bilateral PTEN deletion and led to death in several cases. PTEN-deletion provoked epilepsy was not associated with apparent hippocampal neuron death; supra-granular mossy fiber sprouting was observed in a few mice. In summary, focal, unilateral deletion of PTEN in the adult dentate gyrus suffices to provoke time-dependent emergence of a hyperexcitable circuit generating hippocampus-origin, generalizing spontaneous seizures, providing a novel model for studies of adult-onset epileptogenesis.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106736"},"PeriodicalIF":5.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of hypoactive parvalbumin-positive fast-spiking interneurons restores dentate inhibition to reduce electrographic seizures in the mouse intrahippocampal kainate model of temporal lobe epilepsy","authors":"Sang-Hun Lee ,&nbsp;Young-Jin Kang ,&nbsp;Bret N. Smith","doi":"10.1016/j.nbd.2024.106737","DOIUrl":"10.1016/j.nbd.2024.106737","url":null,"abstract":"<div><div>Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus. The development of compensatory modifications related to PV+ interneuron circuits in the months following status epilepticus is unknown, although reduced dentate GABAergic inhibition persists long after status epilepticus. We employed whole-cell patch-clamp recordings from dentate PV+ interneurons and DGCs in slices from male and female sham controls and intrahippocampal kainate (IHK) treated mice that developed spontaneous seizures months after status epilepticus to study epilepsy-associated changes in dentate PV+ interneuron circuits. Electrical recordings showed that: 1) Action potential firing rates of dentate PV+ interneurons were reduced in IHK treated mice up to four months after status epilepticus; 2) spontaneous inhibitory postsynaptic currents (sIPSCs) in DGCs exhibited reduced frequency but increased amplitude in IHK treated mice; and 3) the amplitude of IPSCs in DGCs evoked by optogenetic activation of dentate PV+ cells was upregulated without changes in short-term plasticity. Video-EEG recordings revealed that IHK treated mice showed spontaneous electrographic seizures in the dentate gyrus and that chemogenetic activation of PV+ interneurons abolished electrographic seizures. Our results suggest not only that the compensatory changes in PV+ interneuron circuits develop after IHK treatment, but also that increased PV+ interneuron mediated inhibition in the dentate gyrus may compensate for cell loss and reduced intrinsic excitability of dentate PV+ interneurons to stop seizures in temporal lobe epilepsy.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106737"},"PeriodicalIF":5.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wireless optogenetic stimulation on the prelimbic to the nucleus accumbens core circuit attenuates cocaine-induced behavioral sensitization","authors":"Min Jeong Ku ,&nbsp;Choong Yeon Kim ,&nbsp;Jong Woo Park ,&nbsp;Seohyeon Lee ,&nbsp;Eun Young Jeong ,&nbsp;Jae-Woong Jeong ,&nbsp;Wha Young Kim ,&nbsp;Jeong-Hoon Kim","doi":"10.1016/j.nbd.2024.106733","DOIUrl":"10.1016/j.nbd.2024.106733","url":null,"abstract":"<div><div>Behavioral sensitization is defined as the heightened and persistent behavioral response to repeated drug exposure as a manifestation of drug craving. Psychomotor stimulants such as cocaine can induce strong behavioral sensitization. In this study, we explored the effects of optogenetic stimulation of the prelimbic (PL) to the nucleus accumbnes (NAc) core on the expression of cocaine-induced behavioral sensitization. Using wireless optogenetics, we selectively stimulated the PL-NAc core circuit, and assessed the effects of this treatment on cocaine-induced locomotor activity and accompanying changes in neuronal activation and dendritic spine density. Our findings revealed that optogenetic stimulation of the PL-NAc core circuit effectively suppressed the cocaine-induced locomotor sensitization, accompanied by a reduction in c-Fos expression within the NAc core. Moreover, optogenetic stimulation led to reduction in dendritic spine density, particularly thin and mushroom spine densities, in the NAc core. This study demonstrates that cocaine-induced locomotor sensitization can be regulated by optogenetic stimulation of the PL-NAc core circuit, providing insights into the crucial role of this circuit in psychomotor stimulant addiction.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106733"},"PeriodicalIF":5.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The broad spectrum of malignant syndromes","authors":"Martina Cuccarelli ,&nbsp;Alessandro Zampogna ,&nbsp;Antonio Suppa","doi":"10.1016/j.nbd.2024.106734","DOIUrl":"10.1016/j.nbd.2024.106734","url":null,"abstract":"<div><div>Malignant syndromes represent a group of medical conditions characterized by a rapid evolution of clinical manifestations, potentially leading to life-threatening complications if left untreated. These syndromes pose significant challenges for diagnosis and management, as they can lead to multisystem organ failure and death. Despite distinct features and origins, these syndromes share similar clinical presentation, pathophysiology, and the imperative for urgent medical intervention. While distinct mechanisms may initially trigger the different malignant syndromes, a final common pathway leading to similar signs and symptoms involves various neurotransmitter systems, including dopaminergic, serotonergic, GABAergic, glycinergic, and glutamatergic pathways. This narrative review examines the clinical presentations and potential causes of malignant syndromes, both highlighting shared pathophysiological mechanisms and emphasizing the critical importance of early recognition and intervention to mitigate potentially fatal outcomes. Although clinically heterogeneous, with variable motor and non-motor manifestations, most malignant syndromes share acute and rapid disruptions in physiological functions, including body temperature regulation, metabolism, control of the autonomic system and maintenance of consciousness. The potential for severe morbidity and mortality associated with these syndromes emphasizes the critical need for understanding their clinical characteristics, underlying mechanisms, and appropriate management strategies.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106734"},"PeriodicalIF":5.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system","authors":"Tadros A. Hana ,&nbsp;Veronika G. Mousa ,&nbsp;Alice Lin ,&nbsp;Rawan N. Haj-Hussein ,&nbsp;Andrew H. Michael ,&nbsp;Madona N. Aziz ,&nbsp;Sevinch U. Kamaridinova ,&nbsp;Sabita Basnet ,&nbsp;Kiel G. Ormerod","doi":"10.1016/j.nbd.2024.106732","DOIUrl":"10.1016/j.nbd.2024.106732","url":null,"abstract":"<div><div>Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed in the <em>Drosophila melanogaster</em> nervous system with varying polyQ lengths, non-pathogenic-htt (NP-htt) and pathogenic-htt (P-htt), with an N-terminal RFP tag for <em>in vivo</em> visualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 h post hatching and significant aggregates form in the segmental nerve branches at 48 h post hatching. Organelle trafficking up- and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106732"},"PeriodicalIF":5.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of Wharton's jelly-derived mesenchymal stem cells and insulin on Schwann cell proliferation in Charcot-Marie-Tooth disease type 1A treatment","authors":"Shin Ji Oh ,&nbsp;Hyeongseop Kim ,&nbsp;Sang Eon Park ,&nbsp;Jeong Hee Kim ,&nbsp;Yong Jun Kim ,&nbsp;Suk-joo Choi ,&nbsp;Soo-young Oh ,&nbsp;Hong Bae Jeon ,&nbsp;Jong Wook Chang","doi":"10.1016/j.nbd.2024.106725","DOIUrl":"10.1016/j.nbd.2024.106725","url":null,"abstract":"<div><div>Charcot-Marie-Tooth disease type 1A (CMT1A) is a demyelinating disease caused by <em>PMP22</em> duplication and an exceedingly rare hereditary peripheral neuropathy, with an incidence of 1 in 2500. Currently, no cure exists for CMT1A; however, various therapeutic approaches are under development. Considering the known therapeutic effects of mesenchymal stem cells (MSCs) and the relation of blood sugar levels with nerve damage in CMT, this study aimed to confirm the therapeutic effects of MSCs and insulin on CMT, using both <em>in-vitro</em> and <em>in-vivo</em> models. CMT1A <em>in-vitro</em> models were exposed to Wharton's jelly-derived MSCs (WJ-MSCs) or insulin, and the resulting proliferation changes were measured. CMT1A mice were treated with WJ-MSCs or insulin, and their phenotypic changes were observed. We observed improvements in myelination of Schwann cells <em>in vitro</em> and motor function <em>in vivo</em>. Insulin also showed therapeutic efficacy by promoting Schwann cell proliferation. Furthermore, combination therapy using insulin and WJ-MSCs was more effective than WJ-MSCs or insulin alone. Insulin promoted the proliferation of Schwann cells and WJ-MSCs through activation of the ATK and PI3K-MAPK signaling pathways. Overall, this study is the first to confirm the therapeutic efficacy of WJ-MSCs and insulin in CMT1A, and their synergistic effect without causing insulin resistance.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106725"},"PeriodicalIF":5.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the alteration of MAP2 interactome caused by a schizophrenia-associated phosphorylation","authors":"J. Lyu ,&nbsp;M.L. MacDonald ,&nbsp;S. Ruiz ,&nbsp;S. Chou ,&nbsp;J. Gilardi ,&nbsp;S.C. Buchwald ,&nbsp;M.J. Grubisha ,&nbsp;R.A. Sweet","doi":"10.1016/j.nbd.2024.106731","DOIUrl":"10.1016/j.nbd.2024.106731","url":null,"abstract":"<div><div>Microtubule-associated protein 2 (MAP2) is a crucial regulator of dendritic structure and neuronal function, orchestrating diverse protein interactions within the microtubule network. We have shown MAP2 is hyperphosphorylated at serine 1782 (S1782) in schizophrenia and phosphomimetic mutation of S1782 in mice (MAP2^S1782E) is sufficient to impair dendritic architecture. We sought to determine how this hyperphosphorylation affects the MAP2 interactome to provide insights into the disorder's mechanisms. We investigated the MAP2 interactome using co-immunoprecipitation and mass spectrometry in MAP2^S1782E and MAP2^WT mice. We found that S1782E MAP2 led to a substantial disruption of protein-protein interactions relative to WT MAP2. Reduced interactions with PDZ domain-containing proteins, calmodulin-binding proteins, ribosome proteins, and kinesin proteins may all contribute to dendritic impairments induced by S1782E, and may be linked to schizophrenia pathogenesis. Interestingly, novel gain-of-function interactions with PPM1L and KLHL8 nominated these as regulators of phosphoS1782 MAP2 abundance and potential therapeutic targets in schizophrenia.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106731"},"PeriodicalIF":5.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking human cerebral and ocular waste clearance: Insights from tear fluid and ultra-high field MRI","authors":"Merel M. van der Thiel ,&nbsp;Nienke van de Sande ,&nbsp;Anouk Meeusen ,&nbsp;Gerhard S. Drenthen ,&nbsp;Alida A. Postma ,&nbsp;Rudy M.M.A. Nuijts ,&nbsp;Noa van der Knaap ,&nbsp;Inez H.G.B. Ramakers ,&nbsp;Carroll A.B. Webers ,&nbsp;Walter H. Backes ,&nbsp;Marlies Gijs ,&nbsp;Jacobus F.A. Jansen","doi":"10.1016/j.nbd.2024.106730","DOIUrl":"10.1016/j.nbd.2024.106730","url":null,"abstract":"<div><div>Impaired cerebral waste clearance (i.e., glymphatics) is evident in aging and neurodegenerative disorders, such as Alzheimer's disease, where an impaired waste clearance system could be related to the accumulation of pathological proteins (e.g., tau). One marker of impaired cerebral clearance is the abundance of enlarged perivascular spaces (PVS). Preclinical studies propose a similar clearance system in the eye, driven by intraocular pressure (IOP). This cross-sectional pilot study explores the link between ocular and cerebral waste clearance by examining the association between MRI-visible PVS, tear fluid total-tau, and IOP.</div><div>Thirty cognitively healthy participants, all aged over 55 years, underwent 7 Tesla MRI, with PVS visually rated in the centrum semiovale (CSO) and basal ganglia. Tear fluid was collected using paper Schirmer's strips and analyzed for total-tau using enzyme-linked immunosorbent assay. IOP was measured using non-contact tonometry. Partial Spearman's correlation coefficients of eye and brain markers were calculated, adjusted for age, sex, tear fluid-wetting length, and hemispheric region of interest volume.</div><div>Higher CSO PVS scores in the left and right hemisphere were associated with higher levels of tear fluid total-tau. Higher CSO PVS scores in both hemispheres were related to lower ipsilateral IOP. The exploratory results suggest that higher tear fluid total-tau and a reduced driving force of ocular waste clearance are connected to impaired cerebral waste clearance in cognitive healthy individuals. This study connects the potential ocular glymphatic system to the cerebral waste clearance system. Clarifying waste clearance biology and validating eye biomarkers for cerebral waste clearance could provide treatment targets and diagnostic opportunities for neurological diseases.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"203 ","pages":"Article 106730"},"PeriodicalIF":5.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRRK2 and RAB8A regulate cell death after lysosomal damage in macrophages through cholesterol-related pathways","authors":"Josefine Fussing Tengberg ,&nbsp;Francesco Russo ,&nbsp;Tau Benned-Jensen ,&nbsp;Jacob Nielsen","doi":"10.1016/j.nbd.2024.106728","DOIUrl":"10.1016/j.nbd.2024.106728","url":null,"abstract":"<div><div>Abstract</div><div>Activating mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are among the most common genetic causes of Parkinson's disease (PD). The mechanistic path from LRRK2 mutations to PD is not established, but several lines of data suggest that LRRK2 modulation of lysosomal function is involved. It has previously been shown that LRRK2 is recruited to lysosomes upon lysosomal damage leading to increased phosphorylation of its RAB GTPase substrates in macrophage-derived RAW 264.7 cells. Here, we find that LRRK2 kinase inhibition reduces cell death induced by the lysosomotropic compound LLOMe in RAW 264.7 cells showing that lysosomal damage and LRRK2 functionally interacts in both directions: lysosomal damage can lead to activation of LRRK2 signaling and LRRK2 inhibition can attenuate LLOMe-induced cell death. The effect is lysosome specific, as only lysosomal stressors and not a variety of other cell death inducers could be modulated by LRRK2 kinase inhibition. We show with timing and Lysotracker experiments that LRRK2 inhibition does not affect the immediate lysosomal permeabilization induced by LLOMe, but rather modulates the subsequent cellular response to lysosomal damage. siRNA-mediated knockdown of LRRK2 and its main substrates, the RAB GTPases, showed that LRRK2 and RAB8A knockdown could attenuate LLOMe-induced cell death, but not other RAB GTPases tested. An RNA sequencing study was done to identify downstream pathways modulated by LLOMe and LRRK2 inhibition. The most striking finding was that almost all cholesterol biosynthesis genes were strongly downregulated by LLOMe and upregulated with LRRK2 inhibition in combination with LLOMe treatment. To explore the functional relevance of the transcriptional changes, we pretreated cells with the NPC1 inhibitor U18666A that can lead to accumulation of lysosomal cholesterol. U18666A-treated cells were less sensitive to LLOMe-induced cell death, but the attenuation of cell death by LRRK2 inhibition was strongly reduced suggesting that LRRK2 inhibition and lysosomal cholesterol reduces cell death by overlapping mechanisms. Thus, our data demonstrates a LRRK2- and RAB8A-mediated attenuation of RAW 264.7 cell death induced by lysosomal damage that is modulated by lysosomal cholesterol.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"202 ","pages":"Article 106728"},"PeriodicalIF":5.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive impairment and amygdala subregion volumes in elderly with cerebral small vessel disease: A large prospective cohort study","authors":"Zhenyu Cheng ,&nbsp;Linfeng Yang ,&nbsp;Jing Li ,&nbsp;Yiwen Chen ,&nbsp;Pengcheng Liang ,&nbsp;Yuanyuan Wang ,&nbsp;Na Wang ,&nbsp;Xinyue Zhang ,&nbsp;Yian Gao ,&nbsp;Chaofan Sui ,&nbsp;Meng Li ,&nbsp;Changhu Liang ,&nbsp;Lingfei Guo","doi":"10.1016/j.nbd.2024.106716","DOIUrl":"10.1016/j.nbd.2024.106716","url":null,"abstract":"<div><div>Although the amygdala is associated with cognitive impairment resulting from cerebral small vessel disease, the relationship between alterations in amygdala structure and cerebral small vessel disease (CSVD) remains controversial. Given that the amygdala comprises several subregions, detecting subtle regional changes through total amygdala volume measurement is challenging. This study aimed to identify the patterns of amygdala subregion atrophy in cerebral small vessel disease patients and their relationship with cognitive impairment. A total of 114 participants diagnosed with cerebral small vessel disease and 129 healthy participants, aged 40 to 70, underwent 3 T magnetic resonance imaging scans. The amygdala subregions were automatically segmented using FreeSurfer. In the Propensity Score Matching (PSM)-matched cohort, Lasso regression was employed to identify subregions associated with cerebral small vessel disease, and restricted cubic splines (RCS) were used to explore their nonlinear relationship with cognitive abilities. Subsequently, multivariate linear regression models were used to investigate the impact of amygdala subregion volumes on various cognitive abilities. Compared to healthy controls (HC), the volume of the left cortical nucleus was significantly reduced in cerebral small vessel disease patients. The volume of the left cortical nucleus was significantly negatively correlated with cerebral small vessel disease progression, and atrophy in this region was also identified as an independent risk factor for decreased cognitive control and processing ability. Our findings suggest that patients with cerebral small vessel disease exhibit atrophy in specific amygdala subregions compared to healthy controls, which correlates with poorer cognitive control and processing abilities. These insights may advance our understanding of the pathogenesis of cerebral small vessel disease.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"202 ","pages":"Article 106716"},"PeriodicalIF":5.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}