Reactivation-dependent amnesia for object recognition memory is contingent on hippocampal theta–gamma coupling during recall

Hippocampal dopamine D1/D5 receptor-dependent destabilization is necessary for object recognition memory (ORM) updating through reconsolidation. Dopamine also regulates hippocampal theta and gamma oscillations, which are involved in novelty and memory processing. We found that, in adult male rats, ORM recall in the presence of a novel object, but not in the presence of a familiar one, triggers hippocampal theta–gamma coupling. Hippocampal theta–gamma coupling (hPAC) does not happen when ORM destabilization is prevented by blocking D1/D5 receptors, but artificial hPAC generation during recall in the presence of a familiar object enables the amnesic effect of reconsolidation inhibitors. Therefore, hPAC controls ORM destabilization, and its modulation could increase reconsolidation-based psychotherapy efficacy.

Powdered Green Tea (Matcha) Attenuates the Cognitive Dysfunction via the Regulation of Systemic Inflammation in Chronic PM2.5-Exposed BALB/c Mice

This study was conducted to evaluate the anti-amnesic effect of the aqueous extract of powdered green tea (matcha) (EM) in particulate matter (PM)2.5-induced systemic inflammation in BALB/c mice. EM ameliorated spatial learning and memory function, short-term memory function, and long-term learning and memory function in PM2.5-induced mice. EM protected against antioxidant deficit in pulmonary, dermal, and cerebral tissues. In addition, EM improved the cholinergic system through the regulation of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activity in brain tissue, and it protected mitochondrial dysfunction by regulating the production of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP contents in brain tissue. EM attenuated systemic inflammation and apoptotic signaling in pulmonary, dermal, olfactory bulb, and hippocampal tissues. Moreover, EM suppressed neuronal cytotoxicity and cholinergic dysfunction in hippocampal tissue. This study suggests that EM might be a potential substance to improve PM2.5-induced cognitive dysfunction via the regulation of systemic inflammation.

Effects of GABAA Receptors in Dorsal Hippocampus on Memory Retention of Cholestatic Rats

The molecular mechanisms that result in cognitive deficits following cholestasis are mainly unknown. As there are many GABAA receptors in the hippocampus CA1 region and the crucial role for GABA in modulating memory, we evaluated the effects of GABAA receptor agents in the CA1 of cholestatic rats on memory retention. The interaction between GABAergic and opioidergic systems in the CA1 on memory was also investigated. The effects of administration of GABAA receptor agonist and antagonist, muscimol (60, 120 and 240 ng/ side) and bicuculline (100, 200 and 400 ng/ side), into CA1 on memory retention were studies using passive avoidance learning (PAL) task in bile duct ligated (BDL) rats. Naloxone (250 ng/ side), the mu-opioid receptor antagonist, was also co-administered alone or with bicuculline (400 ng/ side) to indicate the interaction between opioidergic and GABAergic system. Cholestasis inhibited memory retrieval is shown by the decrease in the step-through latency (STLr). Administration of muscimol or bicuculline alone after training potentiated or attenuated respectively amnesia in BDL rats dose-dependently. Naloxone (250 ng /side) alone increased STLr in BDL-treated rats. Bicuculline (100 ng/side) alone antagonized the amnesic effect of muscimol (120 ng/side). Co-administration of bicuculline and naloxone or muscimol and naloxone caused a significant difference in STLr compared to only naloxone treated rats which show the interaction between two systems on memory retention in cholestssis. Bicuculline (100 ng/side) microinjection alone antagonized the amnesic effect of muscimol (120 ng/side). We indicated the contribution of intra-CA1 GABAA receptors on memory retention in cholestatic rats by the PAL test. Blockade of each GABAA or mu-opioid receptors alone could attenuate the amnesia in BDL rats. Furthermore, blockade of both GABAA or mu-opioid receptors reversed the memory deficit in BDL-treated rats, which shows the interaction between GABAergic and opioidergic systems on memory retention in this test.

Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Mixture of Phlorotannin and Fucoidan from Ecklonia cava Prevents the Aβ-Induced Cognitive Decline with Mitochondrial and Cholinergic Activation

The anti-amnesic effect of a mixture (4:6 = phlorotannin:fucoidan from Ecklonia cava, P4F6) was evaluated on amyloid-beta peptide (Aβ)-induced cognitive deficit mice. The cognitive function was examined by Y-maze, passive avoidance, and Morris water maze tests, and the intake of the mixture (P4F6) showed an ameliorating effect on Aβ-induced learning and memory impairment. After the behavioral tests, superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) contents were confirmed in brain tissue, and in the results, the mixture (P4F6) attenuated Aβ-induced oxidative stress. In addition, mitochondrial activity was evaluated by mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic signaling pathway, and the mixture (P4F6) enhanced mitochondrial function. Furthermore, the mixture (P4F6) effectively regulated tau hyperphosphorylation by regulating the protein kinase B (Akt) pathway, and promoted brain-derived neurotrophic factor (BDNF) in brain tissue. Moreover, in the cholinergic system, the mixture (P4F6) ameliorated acetylcholine (ACh) content by regulating acetylcholinesterase (AChE) activity and choline acetyltransferase (ChAT) expression in brain tissue. Based on these results, we suggest that this mixture of phlorotannin and fucoidan (P4F6) might be a substance for improving cognitive function by effectively regulating cognition-related molecules.

Anti-Amnesic Effect of Curculigo orchioides Plant Extract and Its Function on Acetylcholinesterase Enzyme

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, and one of the most predominant causes of dementia in older people. Preventing acetylcholine from breakdown by an excess amount of acetylcholinesterase is a proven therapy for AD. Traditionally Curculigo orchioides is known for its antioxidant activity, enzyme inhibition activity, and other medicinal uses. In this study, in vitro acetylcholinesterase, inhibitory activity was investigated, and methanolic extract of the plant showed significant activity. This study aims to investigate cholinesterase inhibitory activity, learning, and memory-enhancing activity of Curculigo orchioides. Materials and Methods: The crude methanol extract of the dried powder was prepared by the cold extraction method. In-vitro acetylcholinesterase (AChE) inhibitory activities were determined by the modified Ellman’s method. To confirm learning and memory-enhancing effects, the scopolamine-induced memory impairment Swiss-albino mice were used, and to find the anti-amnesic effect of the extract, a passive shock avoidance task was applied. Results: Results proved that scopolamine-induced cognitive dysfunction decreased significantly by administration of the plant extract solution in the passive avoidance task, and inhibited brain acetylcholinesterase activity. While running an in-vitro AChE inhibitory test the IC50 was 0.782±0.067μg/ml. Conclusion: The results suggested that methanolic extract of Curculigo orchioides can inhibit AChE in-vitro. Besides this, it provides data that proves its ability to improve whole brain AChE activity and enhance memory.

Caesalpinia sappan L. Ameliorates Scopolamine-Induced Memory Deficits in Mice via the cAMP/PKA/CREB/BDNF Pathway

Memory is an essential aspect of human cognition. A decrease in this aspect is well associated with Alzheimer’s disease (AD). The development of a novel cognitive enhancer (CE) may help overcome AD-related problems. In this study, we evaluated the CE effect of Caesalpinia sappan L. (CS) in memory deficit mice. Administration of its ethanolic extract (250 and 500 mg/kg body weight (BW)) and brazilin (5 and 10 mg/kg BW) ameliorated the scopolamine-amnesic effect, as evidenced by significant decreases (p < 0.01, p < 0.05) in the escape latency time and increases (p < 0.01) in the percentage of time spent in the target quadrant of the Morris water maze test. We also examined the cyclic adenosine monophosphate (cAMP) level, protein kinase A (PKA) activity, and protein expression levels of phosphorylated cAMP response element binding (pCREB) and brain-derived neurotrophic factor (BDNF) in hippocampal tissues to elucidate the underlying molecular mechanism. Results showed that CS wood ethanolic extract and brazilin not only significantly increase (p < 0.01, p < 0.05) cAMP levels and PKA activity but also significantly enhance (p < 0.01, p < 0.05) the expression level of pCREB and BDNF in the hippocampus. These findings indicate that CS activates the cAMP/PKA/CREB/BDNF pathway. Taken together, our results demonstrate that CS is a promising herb that could be developed as a CE agent.

Aripiprazole ameliorates scopolamine-induced amnesia in mice

Aripiprazole, a known third generation anti-psychotic drug. The drug has shown to have lesser side effects on extrapyramidal system and enhance memory when compared with the first-generation anti-psychotic drugs. However, studies on the impact of aripiprazole on scopolamine-induced memory impairment in mice have been poorly reported. This study was designed to investigate the impact of aripiprazole on scopolamine-induced amnesia in mice. Thirtysix (36) mice weighing between 20-23g were randomly divided into six groups. Group 1 was given 10 ml/kg distilled water. Group 2 received 3 mg/kg scopolamine alone. Group 3 was given 1 mg/kg donepezil. Group 4 received 0.5 mg/kg aripiprazole. Group 5 was given 0.3 mg/kg aripiprazole. Group 6 received 0.1mg/kg aripiprazole. Thirty minutes after administration of either aripiprazole or donepezil, scopolamine (3 mg/kg) was administered, intraperitoneally. The administration was for 7days, during which their memory was assessed using Morris water maze and Y-maze models. The results showed that the anti-amnesic effect of aripiprazole appeared to be dosedependent; the animals administered with 0.5 mg/kg aripiprazole showed the greatest improved memory performance against scopolamine-induced amnesia. The hippocampal and prefrontal cortex tissues displayed anti-amnesic potential of aripiprazole. Aripiprazole seems to improved memory performance against scopolamine-induced memory impairment in mice. Keywords: Aripiprazole; Anti-amnesic; Scopolamine; Memory