Gene knockout of RNA binding motif 5 in the brain alters RIMS2 protein homeostasis in the cerebellum and Hippocampus and exacerbates behavioral deficits after a TBI in mice
Exp Neurol. 2024 Jan 12;374:114690. doi: 10.1016/j.expneurol.2024.114690. Online ahead of print.ABSTRACTRNA binding motif 5 (RBM5) is a tumor suppressor in cancer but its role in the brain is unclear. We used conditional gene knockout (KO) mice to test if RBM5 inhibition in the brain affects chronic cortical brain tissue survival or function after a controlled cortical impact (CCI) traumatic brain injury (TBI). RBM5 KO decreased baseline contralateral hemispheric volume (p < 0.0001) and exacerbated ipsilateral tissue loss at 21 d after CCI in male mice vs. wild type (WT) (p = 0.0019). CCI injury, but not RBM5 KO, impair...
Source: Experimental Neurology - January 13, 2024 Category: Neurology Authors: Kara Snyder C Edward Dixon Jeremy Henchir Kiersten Gorse Vincent A Vagni Keri Janesko-Feldman Patrick M Kochanek Travis C Jackson Source Type: research
Glucocorticoid receptor antagonist CORT113176 attenuates motor and neuropathological symptoms of Huntington's disease in R6/2 mice
In this study, we evaluated the efficacy of the selective GR antagonist CORT113176 in the commonly used R6/2 mouse model. In male mice, CORT113176 treatment significantly delayed the loss of grip strength, the development of hindlimb clasping, gait abnormalities, and the occurrence of epileptic seizures. CORT113176 treatment delayed loss of DARPP-32 immunoreactivity in the dorsolateral striatum. It also restored HD-related parameters including astrocyte markers in both the dorsolateral striatum and the hippocampus, and microglia markers in the hippocampus. This suggests that CORT113176 has both cell-type and brain region-s...
Source: Experimental Neurology - January 12, 2024 Category: Neurology Authors: Max Gentenaar Fleur L Meulmeester Ximaine R van der Burg Anna T Hoekstra Hazel Hunt Jan Kroon Willeke M C van Roon-Mom Onno C Meijer Source Type: research
PCSK6 exacerbates Alzheimer's disease pathogenesis by promoting MT5-MMP maturation
In this study, we reported that the expression of PCSK6 was significantly increased in the brain tissues of postmortem AD patients and APP23/PS45 transgenic AD model mice, as well as N2AAPP cells. Genetic knockdown of PCSK6 reduced amyloidogenic processing of APP in N2AAPP cells by suppressing the activation of membrane-type 5-matrix metalloproteinase (MT5-MMP), referred to as η-secretase. We further found that PCSK6 cleaved and activated MT5-MMP by recognizing the RRRNKR sequence in its N-terminal propeptide domain in N2A cells. The mutation or knockout of this cleavage motif prevented PCSK6 from interacting with MT5-MMP...
Source: Experimental Neurology - January 12, 2024 Category: Neurology Authors: Mingliang Xu Junjie Li Lei Xia Yehong Du Bin Wu Xiuyu Shi Na Tian Yayan Pang Lilin Yi Mulan Chen Weihong Song Zhifang Dong Source Type: research
Potential links between platelets and amyloid- β in the pathogenesis of Alzheimer's disease: Evidence from in vitro, in vivo, and clinical studies
Exp Neurol. 2024 Jan 9;374:114683. doi: 10.1016/j.expneurol.2024.114683. Online ahead of print.ABSTRACTCerebral amyloid angiopathy (CAA) is a prevalent comorbidity among patients with Alzheimer's disease (AD), present in up to 80% of cases with varying levels of severity. There is evidence to suggest that CAA might intensify cognitive deterioration in AD patients, thereby accelerating the development of AD pathology. As a source of amyloids, it has been postulated that platelets play a significant role in the pathogenesis of both AD and CAA. Although several studies have demonstrated that platelet activation plays an impor...
Source: Experimental Neurology - January 11, 2024 Category: Neurology Authors: Ruedeemars Yubolphan Wasana Pratchayasakul Nut Koonrungsesomboon Nipon Chattipakorn Siriporn C Chattipakorn Source Type: research
Chronic chemogenetic inhibition of TRPV1 bladder afferent promotes micturition recovery post SCI
Exp Neurol. 2024 Jan 8;374:114686. doi: 10.1016/j.expneurol.2024.114686. Online ahead of print.ABSTRACTSpinal cord injury often results in chronic loss of micturition control, which is featured by bladder hyperreflexia and detrusor sphincter dyssynergia. Previous studies showed that treatment of capsaicin reduces non-voiding bladder contractions in multiple animal injury models and human patients. However, its underlying neural mechanisms remain largely unknown. Here, by injecting a RetroAAV into the bladder wall, we specifically targeted TRPV1+, a capsaicin receptor, bladder afferent neurons. Morphometric analysis reveale...
Source: Experimental Neurology - January 10, 2024 Category: Neurology Authors: Long Ma Chen Zhu Yun-Fei Wei Jin-Yong Zhou Min Chen Xin Zhang Ping Zhou Yan Wang Jian Wang Can Chu Jing-Yuan Tang Yan Xu Source Type: research
Insights into neuroinflammatory mechanisms of deep brain stimulation in Parkinson's disease
Exp Neurol. 2024 Jan 8;374:114684. doi: 10.1016/j.expneurol.2024.114684. Online ahead of print.ABSTRACTParkinson's disease, a progressive neurodegenerative disorder, involves gradual degeneration of the nigrostriatal dopaminergic pathway, leading to neuronal loss within the substantia nigra pars compacta and dopamine depletion. Molecular factors, including neuroinflammation, impaired protein homeostasis, and mitochondrial dysfunction, contribute to the neuronal loss. Deep brain stimulation, a form of neuromodulation, applies electric current through stereotactically implanted electrodes, effectively managing motor symptoms...
Source: Experimental Neurology - January 10, 2024 Category: Neurology Authors: Pinar Eser Ersoy Kocabicak Ahmet Bekar Yasin Temel Source Type: research
The acute spinal cord injury microenvironment and its impact on the homing of mesenchymal stem cells
Exp Neurol. 2024 Mar;373:114682. doi: 10.1016/j.expneurol.2024.114682. Epub 2024 Jan 9.ABSTRACTSpinal cord injury (SCI) is a highly debilitating condition that inflicts devastating harm on the lives of affected individuals, underscoring the urgent need for effective treatments. By activating inflammatory cells and releasing inflammatory factors, the secondary injury response creates an inflammatory microenvironment that ultimately determines whether neurons will undergo necrosis or regeneration. In recent years, mesenchymal stem cells (MSCs) have garnered increasing attention for their therapeutic potential in SCI. MSCs no...
Source: Experimental Neurology - January 10, 2024 Category: Neurology Authors: Jinyi Liu Longju Qi Shengzhe Bao Fangsu Yan Jiaxi Chen Shumin Yu Chuanming Dong Source Type: research
DPP-4 inhibition by linagliptin ameliorates age-related mild cognitive impairment by regulating microglia polarization in mice
Exp Neurol. 2024 Mar;373:114689. doi: 10.1016/j.expneurol.2024.114689. Epub 2024 Jan 8.ABSTRACTExtensive preclinical evidence demonstrates a causative link between insulin signaling dysfunction and the pathogenesis of Alzheimer's disease (AD), and diabetic drugs may represent a promising approach to fighting AD. However, it remains to be determined which antidiabetic drugs are more effective in preventing cognitive impairment. Thus, the present study investigated the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on cognitive impairment in middle-aged mice by comparing it with the effect of metformin. We fo...
Source: Experimental Neurology - January 10, 2024 Category: Neurology Authors: Fen Zhuge Liujie Zheng Yuxiang Pan Liyang Ni Zhengwei Fu Junping Shi Yinhua Ni Source Type: research
Quantifying injury expansion in the cervical spinal cord with intravital ultrafast contrast-enhanced ultrasound imaging
This study demonstrates the utility of longitudinal ultrasound imaging as a quantitative tool for tracking injury progression in vivo.PMID:38199511 | DOI:10.1016/j.expneurol.2024.114681 (Source: Experimental Neurology)
Source: Experimental Neurology - January 10, 2024 Category: Neurology Authors: Jennifer N Harmon Jeffrey E Hyde Dylan E Jensen Emma C D'cessare Anton A Odarenko Matthew F Bruce Zin Z Khaing Source Type: research
GPNMB promotes peripheral nerve regeneration by activating the Erk1/2 and Akt pathways via binding Na < sup > + < /sup > /K < sup > + < /sup > -ATPase α1 in Schwann cells
In this study, recombinant human GPNMB (rhGPNMB) was injected into a sciatic nerve injury model. It was found that rhGPNMB facilitated the regeneration and functional recovery of the injured sciatic nerve in vivo. Moreover, it was also confirmed that GPNMB activated the Erk1/2 and Akt pathways via binding with Na+/K + -ATPase α1 (NKA α1) and promoted the proliferation and migration of Schwann cells (SCs) and their expression and secretion of neurotrophic factors and neural adhesion molecules in vitro. Our findings demonstrate that GPNMB facilitates PNR through activation of the Erk1/2 and Akt pathways in SCs by binding w...
Source: Experimental Neurology - January 10, 2024 Category: Neurology Authors: Chao Huang Yani Zheng Ruijuan Ji Liang Qiao Xi Zhang Haiyan Lin Fang Liu Jiajun Xu Yuquan Li Zhiying Zhang Xiangqun Yang Source Type: research
TIE2 expression in hypertensive ICH and its therapeutic modulation with AKB-9778: Implications for brain vascular health
Exp Neurol. 2024 Jan 7;374:114685. doi: 10.1016/j.expneurol.2024.114685. Online ahead of print.ABSTRACTHypertensive intracerebral hemorrhage (ICH) is a devastating condition, the molecular underpinnings of which remain not fully understood. By leveraging high-throughput transcriptome sequencing and network pharmacology analysis, this study unveils the significant role of the tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) in ICH pathogenesis. Compared to controls, a conspicuous downregulation of TIE2 was observed in the cerebral blood vessels of hypertensive ICH mice. In vitro assays with human brain...
Source: Experimental Neurology - January 9, 2024 Category: Neurology Authors: Jingkun Wu Hongbin Wang Naizhu Wang Zai Wang Qinghua Zhu Source Type: research
Distant neuroinflammation acutely induced by focal brain injury and its control by endocannabinoid system
CONCLUSION: The findings show that focal brain injury rapidly triggers widespread parenchymal and extraparenchymal neuroinflammation. The early injury-induced response is likely to represent neurogenic neuroinflammation produced by network hyperexcitability (acute symptomatic seizures). Activation of eCB signaling during acute phase of the brain injury is important for initiation of adaptive anti-inflammatory processes and prevention of chronic pathologic neuroinflammation in distant uninjured structures. However, the beneficial role of injury-induced eCB activity appears to depend on many factors including time, brain reg...
Source: Experimental Neurology - January 8, 2024 Category: Neurology Authors: Anna A Karan Yulia S Spivak Elena M Suleymanova Konstantin A Gerasimov Alex P Bolshakov Lyudmila V Vinogradova Source Type: research
miR-96-5p alleviates cerebral ischemia-reperfusion injury in mice by inhibiting pyroptosis via downregulating caspase 1
In this study, we investigated the efficacy and the mechanism of miR-96-5p in protecting acute ischemic brain injury in adult mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice. MiR-96-5p or the negative control was administered via intracerebroventricular injection. The expression of pyroptosis-related genes and activation of various resident cells in the brain was assessed by RT-qPCR, western blot, immunohistochemistry, and immunofluorescence. Modified neurological severity score, rotarod test, cylinder test, brain water content, and cerebral infarction volume ...
Source: Experimental Neurology - January 8, 2024 Category: Neurology Authors: Fa Jin Lei Jin Boyang Wei Xifeng Li Ran Li Wenchao Liu Shenquan Guo Haiyan Fan Chuanzhi Duan Source Type: research
Distant neuroinflammation acutely induced by focal brain injury and its control by endocannabinoid system
CONCLUSION: The findings show that focal brain injury rapidly triggers widespread parenchymal and extraparenchymal neuroinflammation. The early injury-induced response is likely to represent neurogenic neuroinflammation produced by network hyperexcitability (acute symptomatic seizures). Activation of eCB signaling during acute phase of the brain injury is important for initiation of adaptive anti-inflammatory processes and prevention of chronic pathologic neuroinflammation in distant uninjured structures. However, the beneficial role of injury-induced eCB activity appears to depend on many factors including time, brain reg...
Source: Experimental Neurology - January 8, 2024 Category: Neurology Authors: Anna A Karan Yulia S Spivak Elena M Suleymanova Konstantin A Gerasimov Alex P Bolshakov Lyudmila V Vinogradova Source Type: research
miR-96-5p alleviates cerebral ischemia-reperfusion injury in mice by inhibiting pyroptosis via downregulating caspase 1
In this study, we investigated the efficacy and the mechanism of miR-96-5p in protecting acute ischemic brain injury in adult mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice. MiR-96-5p or the negative control was administered via intracerebroventricular injection. The expression of pyroptosis-related genes and activation of various resident cells in the brain was assessed by RT-qPCR, western blot, immunohistochemistry, and immunofluorescence. Modified neurological severity score, rotarod test, cylinder test, brain water content, and cerebral infarction volume ...
Source: Experimental Neurology - January 8, 2024 Category: Neurology Authors: Fa Jin Lei Jin Boyang Wei Xifeng Li Ran Li Wenchao Liu Shenquan Guo Haiyan Fan Chuanzhi Duan Source Type: research
