scholarly journals Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid β1–42 rat model

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mara A. Guzmán-Ruiz ◽  
Amor Herrera-González ◽  
Adriana Jiménez ◽  
Alan Candelas-Juárez ◽  
Crystal Quiroga-Lozano ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Beta ◽  
Rat Model ◽  
Calcium Binding ◽  
Olfactory Dysfunction ◽  
Olfactory Function ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Arginase 1 ◽  
Olfactory Impairment

Abstract Background Alzheimer’s disease (AD) is characterized by cognitive impairment that eventually develops into dementia. Amyloid-beta (Aβ) accumulation is a widely described hallmark in AD, and has been reported to cause olfactory dysfunction, a condition considered an early marker of the disease associated with injuries in the olfactory bulb (OB), the hippocampus (HIPP) and other odor-related cortexes. Adiponectin (APN) is an adipokine with neuroprotective effects. Studies have demonstrated that APN administration decreases Aβ neurotoxicity and Tau hyperphosphorylation in the HIPP, reducing cognitive impairment. However, there are no studies regarding the neuroprotective effects of APN in the olfactory dysfunction observed in the Aβ rat model. The aim of the present study is to determine whether the intracerebroventricular (i.c.v) administration of APN prevents the early olfactory dysfunction in an i.c.v Amyloid-beta1–42 (Aβ1–42) rat model. Hence, we evaluated olfactory function by using a battery of olfactory tests aimed to assess olfactory memory, discrimination and detection in the Aβ rat model treated with APN. In addition, we determined the number of cells expressing the neuronal nuclei (NeuN), as well as the number of microglial cells by using the ionized calcium-binding adapter molecule 1 (Iba-1) marker in the OB and, CA1, CA3, hilus and dentate gyrus (DG) in the HIPP. Finally, we determined Arginase-1 expression in both nuclei through Western blot. Results We observed that the i.c.v injection of Aβ decreased olfactory function, which was prevented by the i.c.v administration of APN. In accordance with the olfactory impairment observed in i.c.v Aβ-treated rats, we observed a decrease in NeuN expressing cells in the glomerular layer of the OB, which was also prevented with the i.c.v APN. Furthermore, we observed an increase of Iba-1 cells in CA1, and DG in the HIPP of the Aβ rats, which was prevented by the APN treatment. Conclusion The present study describes the olfactory impairment of Aβ treated rats and evidences the protective role that APN plays in the brain, by preventing the olfactory impairment induced by Aβ1–42. These results may lead to APN-based pharmacological therapies aimed to ameliorate AD neurotoxic effects.

scholarly journals Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Dongdong Zhang ◽  
Zhe Wang ◽  
Chenxia Sheng ◽  
Weijun Peng ◽  
Shan Hui ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Amyloid Beta ◽  
Chinese Herb ◽  
Protective Effects ◽  
Amyloid Beta Protein ◽  
Neuroprotective Effects ◽  
Pi3k Inhibitor Ly294002 ◽  
Induced Apoptosis

Icariin is a prenylated flavonol glycoside derived from the Chinese herbEpimedium sagittatumthat exerts a variety of pharmacological activities and shows promise in the treatment and prevention of Alzheimer’s disease. In this study, we investigated the neuroprotective effects of icariin against amyloid beta protein fragment 25–35 (Aβ25–35) induced neurotoxicity in cultured rat pheochromocytoma PC12 cells and explored potential underlying mechanisms. Our results showed that icariin dose-dependently increased cell viability and decreasedAβ25–35-induced apoptosis, as assessed by MTT assay and Annexin V/propidium iodide staining, respectively. Results of western blot analysis revealed that the selective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 suppressed icariin-induced Akt phosphorylation, suggesting that the protective effects of icariin are associated with activation of the PI3K/Akt signaling pathway. LY294002 also blocked the icariin-induced downregulation of proapoptotic factors Bax and caspase-3 and upregulation of antiapoptotic factor Bcl-2 inAβ25–35-treated PC12 cells. These findings provide further evidence for the clinical efficacy of icariin in the treatment of Alzheimer’s disease.

Abstract 173: The Neuroprotective Effect Of JZL184 is Comparable With Therapeutic Hypothermia in a Rat Model of Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
Jennifer Bradley ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Rat Model ◽  
Neuroprotective Effect ◽  
Experimental Studies ◽  
Flow Index ◽  
Protective Effects ◽  
Cerebral Microcirculation ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Introduction: JZL184 is a synthetic monoacylglycerol lipase inhibitor that reduces brain edema, infarct size and alleviates inflammation following cerebral ischemia in experimental studies. In this study, we compared its cerebral protective effects with therapeutic hypothermia following cardiopulmonary resuscitation (CPR) in a rat model. Hypothesis: JZL184 will have similar neuroprotective effects to therapeutic hypothermia after cardiac arrest (CA) by reducing brain and blood brain barrier (BBB) injury and preserving cerebral microcirculation following CPR. Methods: Thirty six male Sprague-Dawley rats weighing between 450-550 g were randomized: 1) control 2) hypothermia 3) JZL184. Ventricular fibrillation was induced and untreated for 6 min for all rats. Resuscitation was attempted with a 4 Joule defibrillation after 8 min of CPR. Immediately following resuscitation, either hypothermia (33+0.5 o C) or JZL184 (16 mg/k, IP) was administered. Cerebral microcirculation, S-100β, NSE and Evan’s Blue (EB) concentrations were analyzed at 6hrs after resuscitation. Results: NSE and S-100β levels were higher in control compared to hypothermia and JZL18 at 6hr post ROSC (p < 0.001) (Fig. 1). Compared with control, there was a significant decrease in brain permeability to EB in Hypothermia and JZL184 after 6hr post ROSC (p<0.001) (Fig. 2). Microvascular flow index (MFI) was reduced in control compared with hypothermia and JZL184 6hr post ROSC (p <0.01). Conclusions: JZL184 administered following resuscitation reduced brain and BBB injury and preserved cerebral microcirculation at 6 hr post arrest to the same extent as hypothermia in a rat model of cardiac arrest.

Relationship between cognitive impairment and olfactory function among older adults with olfactory impairment

2020 ◽  
Author(s):  
Hirokazu Suzuki ◽  
Masaaki Teranishi ◽  
Naomi Katayama ◽  
Tsutomu Nakashima ◽  
Saiko Sugiura ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Olfactory Function ◽  
Olfactory Impairment

scholarly journals ACE2/ANG-(1-7)/Mas Receptor Axis Activation Prevents Inflammation, Glial Activation And Cognitive Decline In a Rat Model of STZ Induced Impairment of Learning and Memory

2021 ◽  
Author(s):  
Virendra Tiwari ◽  
Jitendra Singh ◽  
Priya Tiwari ◽  
Swati Chaturvedi ◽  
Shivangi Gupta ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Rat Model ◽  
Protective Effects ◽  
Ang Ii ◽  
Diminazene Aceturate ◽  
Experimental Conditions ◽  
Mas Receptor ◽  
Amyloid Pathology

Abstract Activation of the renin-angiotensin system (RAS), mediated by Angiotensin converting enzyme/Angiotensin II/Angiotensin receptor-1 (ACE/Ang II/AT1 R) axis elicits amyloid pathology, induces neurodegeneration and cognitive impairment leading to Alzheimer's disease (AD). On the contrary, Angiotensin converting enzyme2 (ACE2) produces Ang -(1-7) which binds with the Mas receptor and counters ACE/Ang II/AT1 axis. To date, the involvement of ACE2/Ang-(1–7)/MasR axis in etiology and progression of AD largely remains to be elucidated. Hence, the present study is aimed to determine the role of ACE2/Ang-(1–7)/MasR axis in STZ induced model of neurodegeneration using Diminazene aceturate (DIZE), an ACE2 activator in both in vitro/in vivo experimental conditions. Interestingly, ROS content and oxidative stress burden in N2A cells were found to be attenuated along with a decrease in enzymatic activity of AChE following DIZE treatment. In contrast, activation of this axis led to altered mitochondrial membrane potential (MMP) in addition to ablated intracellular Ca2+ influx. ACE2/Ang-(1–7)/MasR axis activation further resulted in reduction of astrogliosis as indicated by decreased intensity of NFκB and dwindled expression of its downstream NLRP3 cascade signaling molecules. These results were confirmed by using a selective inhibitor of ACE-2, MLN-4760, which reversed the protective effects of ACE2 activation by DIZE. Subsequently, treatment with DIZE in STZ induced rat model of AD prevented cognitive impairment and progression of amyloid pathology. Therefore, the involvement of ACE2/Ang-(1–7)/Mas axis suggests that it could be further explored as a potential pathway in AD, owing to its inhibitory effect on inflammation/astrogliosis and restoring cognitive functions.

scholarly journals Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Min Xie ◽  
Meijian Wang ◽  
Wei Liu ◽  
Min Xu ◽  
Pan Shang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Type I Diabetes ◽  
Type I ◽  
Protective Effects ◽  
Diabetic Encephalopathy ◽  
Neuroprotective Effects ◽  
Lim Kinase ◽  
Ca1 Region

Diabetic encephalopathy is a type of central diabetic neuropathy resulting from diabetes mainly manifested as cognitive impairments. However, its underlying pathogenesis and effective treatment strategies remain unclear. In the present study, we investigated the effect of Lipin1, a phosphatidic acid phosphatase enzyme, on the pathogenesis of diabetic encephalopathy. We found that in vitro, Lipin1 exerts protective effects on high glucose-induced reductions of PC12 cell viability, while in vivo, Lipin1 is downregulated within the CA1 hippocampal region in a type I diabetes rat model. Increased levels of Lipin1 within the CA1 region are accompanied with protective effects including amelioration of dendritic spine and synaptic deficiencies, phosphorylation of the synaptic plasticity-related proteins, LIM kinase 1 (p-limk1) and cofilin, as well as increases in the synthesis of diacylglycerol (DAG), and the expression of phosphorylated protein kinase D (p-PKD). These effects are associated with the rescue of cognitive disorders as shown in this rat model of diabetes. In contrast, knockdown of Lipin1 within the CA1 region enhanced neuronal abnormalities and the genesis of cognitive impairment in rats. These results suggest that Lipin1 may exert neuroprotective effects involving the PKD/Limk/Cofilin signaling pathway and may serve as a potential therapeutic target for diabetic encephalopathy.

Olfactory dysfunction in familial parkinsonism

Neurology ◽  
1997 ◽  
Vol 49 (5) ◽  
pp. 1262-1267 ◽  
Author(s):  
K. Markopoulou ◽  
K. W. Larsen ◽  
E. K. Wszolek ◽  
M. A. Denson ◽  
A. E. Lang ◽  
...  
Keyword(s):  
At Risk ◽  
Neurodegenerative Disease ◽  
Disease Onset ◽  
Disease Process ◽  
Olfactory Dysfunction ◽  
Olfactory Function ◽  
Phenotypic Characteristic ◽  
Smell Test ◽  
Olfactory Impairment ◽  
The Difference

Impaired olfactory function is commonly observed in idiopathic Parkinson's disease (IPD). However, it is unknown whether it is also found in familial parkinsonism. To address this issue we administered a smell test to 12 affected, three monosymptomatic, and 12 at-risk individuals from six large parkinsonian kindreds. Three kindreds exhibited an IPD phenotype and three exhibited a parkinsonism-plus syndrome (PPS) phenotype. All but one of the affected individuals had impaired olfactory function. In contrast, only five of the 12 at-risk individuals had impaired olfactory function. The degree of olfactory impairment in the at-risk individuals was less severe than in the affected individuals. The difference in the degree of olfactory impairment in individuals exhibiting the IPD and the PPS phenotypes was not statistically significant. These findings suggest that olfactory dysfunction is a phenotypic characteristic of familial parkinsonism and that it is independent of the kindred phenotype. The appearance of olfactory dysfunction soon after disease onset raises the possibility that it is part of the neurodegenerative disease process.

scholarly journals Neuroprotective Effects and Mechanism of β-Asarone against Aβ1–42-Induced Injury in Astrocytes

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Yuanxiao Yang ◽  
Ling Xuan ◽  
Hongshu Chen ◽  
Shijie Dai ◽  
Liting Ji ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Rat Model ◽  
Hippocampal Damage ◽  
Cellular Model ◽  
Neuroprotective Effects ◽  
Aqp4 Expression ◽  
Acorus Tatarinowii

Emerging evidence suggests that activated astrocytes play important roles in AD, and β-asarone, a major component of Acorus tatarinowii Schott, was shown to be a potential therapeutic candidate for AD. While our previous study found that β-asarone could improve the cognitive function of rats hippocampally injected with Aβ, the effects of β-asarone on astrocytes remain unclear, and this study aimed to investigate these effects. A rat model of Aβ1–42 (10 μg) was established, and the rats were intragastrically treated with β-asarone at doses of 10, 20, and 30 mg/kg or donepezil at a dose of 0.75 mg/kg. The sham and model groups were intragastrically injected with an equal volume of saline. Animals were sacrificed on the 28th day after administration of the drugs. In addition, a cellular model of Aβ1–42 (1.1 μM, 6 h) was established, and cells were treated with β-asarone at doses of 0, 2.06, 6.17, 18.5, 55.6, and 166.7 μg/mL. β-Asarone improved cognitive impairment, alleviated Aβ deposition and hippocampal damage, and inhibited GFAP, AQP4, IL-1β, and TNF-α expression. These results suggested that β-asarone could alleviate the symptoms of AD by protecting astrocytes, possibly by inhibiting TNF-α and IL-1β secretion and then downregulating AQP4 expression.

scholarly journals Even cognitively well-functioning adults are unaware of their olfactory dysfunction: Implications for ENT clinicians and researchers

2015 ◽  
Vol 53 (1) ◽  
pp. 89-94
Author(s):  
Eike Wehling ◽  
Astri J. Lundervold ◽  
Thomas Espeset ◽  
Ivar Reinvang ◽  
Annika Bramerson ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Objective Assessment ◽  
Subjective Assessment ◽  
Normal Function ◽  
Olfactory Dysfunction ◽  
Olfactory Function ◽  
Elderly Adults ◽  
Middle Aged ◽  
Sense Of Smell ◽  
Healthy Sample

Background: Past findings of an impact of cognitive impairment on awareness of olfactory dysfunction, and high prevalence of age-associated cognitive impairment motivated the present study of whether middle-aged and elderly adults are unaware of an olfactory dysfunction despite being carefully screened for cognitive impairment. Methodology: The sample included 203 Norwegian participants, aged 46-79 years, 134 women and 69 men, who underwent comprehensive neuropsychological assessment for screening of cognitive impairment. Subjective assessment of olfactory function ("How would you estimate your sense of smell?") was compared with outcome on objective assessment of olfactory function with the Scandinavian Odor Identification Test, which in the present study was shown to be valid for use on Norwegian populations. Results: We found that 79% of this cognitively healthy sample with objectively assessed olfactory dysfunction reported normal olfactory function (57% of functionally anosmics reported normal function). In contrast, only 9% with objectively assessed normal olfactory function reported olfactory dysfunction. Conclusion: A large proportion of cognitively well-functioning middle-aged and elderly adults with an olfactory dysfunction are unaware of their dysfunction. The ENT physician who suspects that the sense of smell may be compromised should, in addition to an anamnesis, assess the patient`s olfactory function objectively.

scholarly journals IL-1Rahigh-IL-4low-IL-13low: A Novel Plasma Cytokine Signature Associated with Olfactory Dysfunction in Older US Adults

2020 ◽  
Vol 45 (5) ◽  
pp. 407-414
Author(s):  
Eli P Darnell ◽  
Kristen E Wroblewski ◽  
Kristina L Pagel ◽  
David W Kern ◽  
Martha K McClintock ◽  
...  
Keyword(s):  
Social Life ◽  
Smoking Status ◽  
Olfactory Dysfunction ◽  
Olfactory Function ◽  
Odor Identification ◽  
Physical Frailty ◽  
Plasma Cytokine ◽  
Cytokine Profiles ◽  
Age Related ◽  
Olfactory Impairment

Abstract Inflammation has been implicated in physical frailty, but its role in sensory impairment is unclear. Given that olfactory impairment predicts dementia and mortality, determining the role of the immune system in olfactory dysfunction would provide insights mechanisms of neurosensory decline. We analyzed data from the National Social Life, Health and Aging Project, a representative sample of home-dwelling older US adults. Plasma levels of 18 cytokines were measured using standard protocols (Luminex xMAP). Olfactory function was assessed with validated tools (n-butanol sensitivity and odor identification, each via Sniffin’ Sticks). We tested the association between cytokine profiles and olfactory function using multivariate ordinal logistic regression, adjusting for age, gender, race/ethnicity, education level, cognitive function, smoking status, and comorbidity. Older adults with the IL-1Rahigh-IL-4low-IL-13low cytokine profile had worse n-butanol odor sensitivity (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19–2.17) and worse odor identification (OR = 1.42, 95% CI 1.11–1.80). Proinflammatory, Th1, or Th2 cytokine profiles were not associated with olfactory function. Moreover, accounting for physical frailty did not alter the main findings. In conclusion, we identified a plasma cytokine signature—IL-1Rahigh-IL-4low-IL-13low—that is associated with olfactory dysfunction in older US adults. These data implicate systemic inflammation in age-related olfactory dysfunction and support a role for immune mechanisms in this process, a concept that warrants additional scrutiny.

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