Scopolamine is a well-known pharmacological agent responsible for causingmemory impairmentin animals, as well as oxidative stress and neuroinflammation inducer which lead to the development of ...Alzheimer disease. Although a cure for Alzheimer’s disease is unavailable. Ranuncoside, a metabolite obtained from a medicinal plant has demonstrated antioxidant and anti-inflammatory properties in vitro, making it a promising treatment with potential anti-Alzheimer disease properties. However, as ranuncoside has not been evaluated for its antioxidant and anti-neuroinflammatory properties in any in vivo model, our study aimed to evaluate its neurotherapeutic efficacy against scopolamine-induced memory impairment in adult male albino mice.
Mice were randomly divided into four experimental groups. Mice of group I was injected with saline, group II was injected with scopolamine (1 mg/kg/day) for 3 weeks. After receiving a daily injection of scopolamine for 1 week, the mice of group III were injected with ranuncoside (10 mg/kg) every other day for 2 weeks along with scopolamine daily and group IV were injected with ranuncoside on 5th alternate days. Behavioral tests (i.e., Morris water maze and Y-maze) were performed to determine the memory-enhancing effect of ranuncoside against scopolamine's memory deleterious effect. Western blot analysis was also performed to further elucidate the anti-neuroinflammatory and antioxidant effects of ranuncoside against scopolamine-induced neuroinflammation and oxidative stress.
Our results showed memory-enhancing, anti-neuroinflammatory effect, and antioxidant effects of ranuncoside against scopolamine by increasing the expression of the endogenous antioxidant system (i.e., Nrf2 and HO-1), followed by blocking neuroinflammatory markers such as NF-κB, COX-2, and TNF-α. The results also revealed that ranuncoside possesses hypoglycemic and hypolipidemic effects against scopolamine-induced hyperglycemia and hyperlipidemia in mice as well as scopolamine’s hyperglycemic effect. In conclusion, our findings suggest that ranuncoside could be a potential agent for the management of Alzheimer’s disease, hyperglycemia, and hyperlipidemia.
Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific ...hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients.
From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes.
Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23-0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group.
Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients.
Alzheimer's disease (AD) is a progressive developmental neurodegenerative disease that primarily develops in old age. Memory impairment is an important manifestation of AD. It has been demonstrated ...that inflammation and oxidative stress are important mediators in the development and progression of AD. Codonopsis Radix (CR) has a long history of consumption, exhibiting lots of beneficial health effects, including anti-ageing, antioxidant, and anti-inflammatory properties. However, studies on the effects of CR on scopolamine-induced amnesia have rarely been reported.
The aim of this study was to investigate the ameliorative effect of macromolecular portion (polysaccharides, POL) and small molecule portion (fine extract rich in phenylpropanoids-polyacetylenes, EPP) from CR on improving scopolamine-induced memory impairment and to elucidate the potential mechanism of action.
C57BL/6 mice were pretreated with EPP (0.2, 0.4, and 0.6 g/kg), POL (0.3, 0.6, and 0.9 g/kg), and donepezil (5 mg/kg) by gavage for 7 days, followed by intraperitoneal injection of scopolamine (1 mg/kg) to induce memory impairment. The 16S rRNA gene sequencing, histopathological, western blotting, and biochemical analysis (various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation) were performed to further elucidate the mechanism of action. Moreover, the acetylcholinesterase (AChE) inhibitory activities of POL, EPP, and its main compounds tangshenoside I, lobetyol, lobetyolin, and lobetyolinin were evaluated.
Experiments have confirmed that both POL and EPP from CR could improve scopolamine-induced spatial learning memory deficits. Both of them could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities. They also could enhance antioxidant defense via increasing the activities of superoxide dismutase and glutathione peroxidase, and anti-inflammatory function through suppressing inflammatory factors (nitric oxide, TNF-α, and IL-6) and regulating gut flora. Besides, in vitro experiments demonstrated that four monomeric compounds and EPP, except POL, exhibited inhibition of AChE activity.
EPP and POL from CR exert a beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. CR may be a promising medicine for preventing and improving learning memory.
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•EPP and POL are important active ingredients in Codonopsis Radix.•EPP and POL can ameliorate scopolamine-induced cognitive impairment.•EPP and POL can ameliorate memory impairment by modulating multiple pathways.
Mild Cognitive Impairment Sanford, Angela M
Clinics in geriatric medicine,
08/2017, Letnik:
33, Številka:
3
Journal Article
Recenzirano
Mild cognitive impairment (MCI) occurs along a continuum from normal cognition to dementia. A roadblock to earlier diagnosis and potential treatment is the lack of consistency with screening for MCI. ...Universal screening would be ideal, but is limited. Once a diagnosis of MCI is made, it is important for the clinician to evaluate for reversible causes. At present time, there are no pharmacologic treatments proven to slow or cure progression of MCI to dementia; nonetheless, there is evidence that lifestyle modifications including diet, exercise, and cognitive stimulation may be effective.
•• Lipopolysaccharide induced a neuroinflammation and oxidative stress status.•Neuroinflammation was accompanied with learning and memory impairment.•Neuroinflammation decreased BDNF while increased ...GFAP in the hippocampus.•Acetyl-11-keto-β-boswellic acid(AKBA) showed anti-inflammatory effects.•AKBA improved memory and BDNF while decreased GFAP in the hippocampus.
The therapeutic effects of the olibanum, the resin of Boswellia serrata on inflammatory diseases have been reported. There are more than 200 active ingredients in this resin including acetyl-11-keto-β-boswellic acid (AKBA). We proposed that AKBA can improve memory impairment induced by cerebral inflammation following the administration of lipopolysaccharide (LPS). Forty male rats were grouped and received the following treatments: Control (diluted DMSO + saline), LPS (diluted DMSO + 1 mg/kg LPS), LPS- AKBA 5 and LPS- AKBA 10 (5 or 10 mg/ kg AKBA before LPS). Morris water maze (MWM), passive avoidance (PA) and biochemical tests were carried out. Pre-treatment with both doses of AKBA improved memory performance in MWM and PA tests (P < 0.05 to P < 0.001). Pre-treatment by AKBA improved the levels of hippocampal IL-10 (P < 0.001), BDNF (P < 0.001), CAT (P < 0.05 and P < 0.001), SOD P < 0.001 and thiols (P < 0.01 and P < 0.001) while reduced IL-6 (P < 0.001), TNF-α (P < 0.001), NO (P < 0.05 and P < 0.001), GFAP (P < 0.001) and MDA (P < 0.001) levels. AKBA effectively ameliorated LPS-induced learning and memory impairments and improved BDNF in a neuroinflammation animal model. The effects seem to be due to setting a positive balance between pro-inflammatory to inflammatory cytokines and reinvigorate the antioxidant system.
In this work, we have developed a novel series of multi-target-directed ligands to address low levels of acetylcholine (ACh), oxidative stress, metal ion dysregulation, and the misfolded proteins. ...Novel apigenin-donepezil derivatives, naringenin-donepezil derivatives, genistein-donepezil derivatives and chalcone-donepezil derivatives have been synthesized, in vitro results showed that TM-4 was a reversible and potent huAChE (IC50 = 0.36 μM) and huBChE (IC50 = 15.3 μM) inhibitor, and showed potent antioxidant activity (ORAC = 1.2 eq). TM-4 could significantly inhibit self-induced Aβ1-42 aggregation (IC50 = 3.7 μM). TM-4 was also an ideal neuroprotectant, potential metal chelation agent, and it could inhibit and disaggregate huAChE-induced and Cu2+-induced Aβ aggregation. Moreover, TM-4 could activate UPS degradation pathway in HT22 cells and induce autophagy on U87 cells to clear abnormal proteins associated with AD. More importantly, TM-4 could cross BBB in vitro assay. In addition, in vivo assay revealed that TM-4 exhibited remarkable dyskinesia recovery rate and response efficiency on AlCl3-induced zebrafish AD model, and TM-4 indicated surprising protective effect on Aβ1-40-induced vascular injury. TM-4 presented precognitive effect on scopolamine-induced memory impairment. And the regulation of multi-targets for TM-4 were further conformed through transcriptome sequencing. More interesting, the blood, urine and feces metabolism in rat and rat/human liver microsome metabolism towards TM-4 were also investigated. Overall, TM-4 is a promising multi-function candidate for the development of drugs to Alzheimer’s disease.
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•TM-4 was a promising multi-function agent.•TM-4 improve AlCl3-induced zebrafish AD.•TM-4 protect Aβ1-40-mediated zebrafish vascular injury.•TM-4 improve scopolamine-induced memory impairment.•The transcriptome sequencing and metabolism of TM-4 were also investigated.
•Sleep deprivation (SD) impairs learning and memory.•SD causes oxidative stress and neuroinflammation.•Pretreatment with sericin prevented SD induced memory impairment.•Sericin attenuated SD induced ...neuroinflammation and oxidative stress.•Sericin restored levels of presynaptic and postsynaptic proteins.
Sleep deprivation (SD) induces learning and memory deficits via inflammatory responses and oxidative stress. On the other hand, sericin (Ser) possesses potent antioxidant and neuroprotective effects. We investigated the effect of different doses of Ser on the SD-induced cognitive impairment. Ser (100, 200, and 300 mg/kg) was administered to animals via oral gavage for 8 days, 5 days before to SD, and during SD. SD was induced in mice using a modified multiple platform model, starting on the 6th day for 72 h. Spatial learning and memory were assessed using the Lashley III maze. Serum corticosterone level, and hippocampal malondialdehyde (MDA), total antioxidant capacity (TAC), and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were evaluated. The expression of growth‐associated protein 43 (GAP-43), post‐synaptic density‐95 (PSD-95), synapsin 1 (SYN-1), and synaptophysin (SYP), and inflammation markers were detected by western blotting. SD caused cognitive impairment, while Ser pretreatment prevented such an effect. Serum corticosterone also increased with SD, but its levels were suppressed in SD mice receiving Ser. Furthermore, Ser normalized SD-induced reduction in the hippocampus activity of SOD and GPx, increased TAC, and decreased MDA levels. Besides, Ser pretreatment increased GAP-34, SYP, SYN-I, and PSD-95 and reduced IL1-β and TNF-α in the hippocampus. SD induced memory impairment and pretreatment with Ser improved memory via its antioxidant, anti-inflammation, and up-regulation of synaptic proteins in the hippocampus.
Smartphones are a fundamental part of modern life and have resulted in a vast increase in photo-taking. How smartphone use can affect cognitive processes, including memory, is poorly understood, but ...research shows taking photographs can result in a photo-taking-impairment effect. Across 3 laboratory experiments, we aimed to replicate the impairment effect and shed light into the underlying mechanisms by manipulating encoding type (intentional vs. incidental) and recognition stimuli (zoomed-in vs. complete paintings). During the presentation of a mock museum tour, participants observed or photographed presented artworks. In Experiment 1 and 3 following intentional encoding, a photo-taking impairment effect impacting accuracy and confidence was observed. In Experiment 2, this impairment effect did not persist when encoding was incidental. Zoomed-in images did not modulate the photo-taking-impairment effect in Experiment 3. Results are discussed in relation to cognitive offloading and attentional disengagement hypotheses and appear to oppose attentional disengagement as a contributing mechanism.
Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. ...(Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.
Research investigating how subjective cognitive complaints (SCCs) might reliably indicate impairments in objective cognitive functioning has produced highly varied findings, and despite attempts to ...synthesise this literature (e.g., Jonker et al.
International Journal of Geriatric Psychiatry, 15
, 983–991,
2000
; Reid and MacLullich
Dementia and Geriatric Cognitive Disorders, 22
(5–6), 471–485,
2006
; Crumley et al.
Psychology and Aging, 29
(2), 250–263,
2014
), recent work continues to offer little resolution. This review provides both quantitative and qualitative synthesis of research conducted since the last comprehensive review in 2006, with the aim of identifying reasons for these discrepancies that might provide fruitful avenues for future exploration. Meta-analysis found a small but significant association between SCCs and objective cognitive function, although it was limited by large heterogeneity between studies and evidence of potential publication bias. Often, assessments of SCCs and objective cognitive function were brief or not formally validated. However, studies that employed more comprehensive SCC measures tended to find that SCCs were associated independently with both objective cognitive function and depressive symptoms. Further explicit investigation of how assessment measures relate to reports of SCCs, and the validity of the proposed ‘compensation theory’ of SCC aetiology, is recommended.
