Abscisic acid ameliorates motor disabilities in 6-OHDA-induced mice model of Parkinson's disease.

Parkinson's disease (PD) is characterized by a myriad of symptoms, encompassing both motor disabilities and cognitive impairments. Recent research has shown that abscisic acid (ABA) is a phytohormone found in various brain regions of several mammals and exhibits neuroprotective properties. To investigate the effects of ABA on cognitive and motor disorders, a mouse model of PD was utilized. The administration of 6-hydroxydopamine (6-OHDA) to the lateral ventricles was conducted, with ABA (10 and 15 µg/mouse, i. c.v.) being administered for one week after the 6-OHDA injection for 4 days. Motor and cognitive performance were evaluated through the use of open field, rotarod, wire grip, and shuttle box tests. The results indicated that cognitive function and motor disorders were significantly impaired in 6-OHDA-treated animals. However, in mice treated with 6-OHDA, ABA (15 µg/mouse) significantly reversed balance and muscle strength deficits. It should be noted that the administration of ABA did not significantly improve cognitive impairment or rearing in Parkinsonism mice. Therefore, the findings suggest that ABA plays a crucial role in protecting mice from motor disabilities caused by 6-OHDA.

The hyperexcitability of laterodorsal tegmentum cholinergic neurons accompanies adverse behavioral and cognitive outcomes of prenatal stress.

Exposure to prenatal stress (PS) leads to the offspring's vulnerability towards the development of cognitive and behavioral disorders. Laterodorsal tegmentum (LDT) is a part of the brainstem cholinergic system that is believed to play a pivotal role in the stress-associated progression of anxiety, memory impairment, and addictive behaviors. In this study, we aimed to investigate the electrophysiological alterations of LDT cholinergic neurons and its accompanied behavioral and cognitive outcomes in the offspring of mice exposed to physical or psychological PS. Swiss Webster mice were exposed to physical or psychological stress on the tenth day of gestation. Ex vivo investigations in LDT brain slices of adolescent male offspring were performed to evaluate the effects of two stressor types on the activity of cholinergic neurons. Open field test, elevated plus maze, passive avoidance test, and conditioned place preference were conducted to assess behavioral and cognitive alterations in the offspring. The offspring of both physical and psychological PS-exposed mice exhibited increased locomotor activity, anxiety-like behavior, memory impairment, and preference to morphine. In both early- and late-firing cholinergic neurons of the LDT, stressed groups demonstrated higher firing frequency, lower adaptation ratio, decreased action potential threshold, and therefore increased excitability compared to the control group. The findings of the present study suggest that the hyperexcitability of the cholinergic neurons of LDT might be involved in the development of PS-associated anxiety-like behaviors, drug seeking, and memory impairment.

Central injection of abscisic acid attenuates mood disorders induced by subchronic stress in male mice.

Stressful life increases the risk of mental and psychological disorders and cognitive deficits. Abscisic acid (ABA) is a plant hormone that has been recently discovered in mammalians. ABA is produced in response to stressful stimuli and it can reduce anxiety-like behaviors and depression and improve cognitive function. This study was designed to evaluate the effects of microinjection of ABA on depression, anxiety, passive avoidance learning and memory deficits induced by subchronic stress. ABA (10 and 15  µ $\umu $ g/mouse, i.c.v.) was administered one week after recovery period for 4 consecutive days. A three-session forced swimming test (FST) protocol for induction of subchronic stress was administered to the mice. Exploratory, anxiety-like behavior, depression and cognitive function were assessed 24 h after the last swim stress session. The results indicated that ABA (15  µ $\umu $ g/mouse) could ameliorate anxiety and depression induced by FST. In addition, ABA had no effect on the subchronic stress-induced cognitive impairments. Taken together, the results suggest that ABA could improve anxiety and depression induced by subchronic stress.

Phytohormone abscisic acid elicits positive effects on harmaline-induced cognitive and motor disturbances in a rat model of essential tremor.

OBJECTIVE: Essential tremor (ET) as a neurological disorder is accompanied by cognitive and motor disturbances. Despite the high incidence of ET, the drug treatment of ET remains unsatisfactory. Recently, abscisic acid (ABA) has been reported to have positive neurophysiological effects in mammals. Here, the effects of ABA on harmaline-induced motor and cognitive impairments were investigated in rats. METHODS: Male Wistar rats weighing 120-140 g were divided into control, harmaline (30 mg/kg, ip), ABA vehicle (DMSO+normal saline), and ABA (10 µg/rat, icv, 30 min before harmaline injection) groups. Exploratory, balance and motor performance, anxiety, and cognitive function were assessed using footprint, open field, wire grip, rotarod, and shuttle box tests. RESULTS: The results indicated that ABA (10 µg/rat) can improve harmaline-induced tremor in rats. The administration of ABA significantly increased time spent on wire grip and rotarod. In addition, ABA had a promising effect against the cognitive impairments induced by harmaline. CONCLUSION: Taken together, ABA has positive effects on locomotor and cognitive impairments induced by tremor. However, further studies are required to determine the exact mechanisms of ABA on the ET.

Preparation and evaluation of crocin loaded in nanoniosomes and their effects on ischemia-reperfusion injuries in rat kidney.

As a powerful antioxidant compound, crocin can partially protect against renal ischemia/reperfusion (I/R) injuries. The encapsulation of components in niosomes (non-ionic surfactant-based vesicle) as nano-sized carrier systems has been proposed as they improve the solubility, stability, and bioavailability of drugs. Herein, the encapsulation of crocin in nano-niosomes and the effects of crocin-loaded nano-niosomes on renal ischemia/reperfusion-induced damages were evaluated. Nano-niosomes containing crocin were formulated by a modified heating method and were characterized for their physicochemical characteristics. Ischemia was induced by clamping the renal artery for 30 min followed by 1 or 24 h of reperfusion. Rats received an intra-arterial injection of nano-niosome-loaded crocin at the outset of reperfusion. Blood samples were taken after reperfusion to measure urea, creatinine (Cr), malondialdehyde (MDA), and superoxide dismutase (SOD) activity. The right kidney was removed for histological examination. The results showed that crocin-contain nano-niosomes have appropriate size and morphology, acceptable encapsulation efficiency, and a proper release pattern of crocin. I/R enhanced creatinine (Cr), urea, and malondialdehyde (MDA) serum levels and reduced SOD activity and histological damages in the renal tissue.

Using Micro- and Macro-Level Network Metrics Unveils Top Communicative Gene Modules in Psoriasis.

(1) Background: Psoriasis is a multifactorial chronic inflammatory disorder of the skin, with significant morbidity, characterized by hyperproliferation of the epidermis. Even though psoriasis' etiology is not fully understood, it is believed to be multifactorial, with numerous key components. (2) Methods: In order to cast light on the complex molecular interactions in psoriasis vulgaris at both protein-protein interactions and transcriptomics levels, we studied a set of microarray gene expression analyses consisting of 170 paired lesional and non-lesional samples. Afterwards, a network analysis was conducted on the protein-protein interaction network of differentially expressed genes based on micro- and macro-level network metrics at a systemic level standpoint. (3) Results: We found 17 top communicative genes, all of which were experimentally proven to be pivotal in psoriasis, which were identified in two modules, namely the cell cycle and immune system. Intra- and inter-gene interaction subnetworks from the top communicative genes might provide further insight into the corresponding characteristic interactions. (4) Conclusions: Potential gene combinations for therapeutic/diagnostics purposes were identified. Moreover, our proposed workflow could be of interest to a broader range of future biological network analysis studies.

Progressive age-dependent motor impairment in human tau P301S overexpressing mice.

This study assessed the development of motor deficits in female hTau.P301S transgenic mice from 1.5 to 5.5 months of age. The test battery included clasping reflex, grid hanging, Rotarod test, spontaneous explorative activity, Catwalk gait analysis, and nest building. Starting from the age of 2-3 months the mice showed marked hyperactivity, abnormal placing of weight on the hindlimbs and defective nest building in their home cage. These behavioral impairments did not progress with age. In addition, there was a progressive development of hindlimb clasping, inability to stay on a rotating rod or hang on a metal grid, and gait impairment. Depending on the measured output parameter, the motor impairment became significant from 3 to 4 months onwards and rapidly worsened until the age of 5.5 months with little inter-individual variation. The progressive motor impairment was paralleled by a robust increase in AT8 p-tau positive neurons in deep cerebellar nuclei and pontine brainstem between 3 and 5.5 months of age. The quick and steadily progressive motor impairment between 3 and 5.5 months of age accompanied by robust development of tau pathology in the hindbrain makes this mouse well suited for preclinical studies aiming at slowing down tau pathology associated with primary or secondary tauopathies.

Ginger Extract Reduces Chronic Morphine-Induced Neuroinflammation and Glial Activation in Nucleus Accumbens of Rats.

BACKGROUND: Chronic usage of morphine elicits the production of inflammatory factors by glial cells and induces neuroinflammation. Ginger (Zingiber Officinale Roscoe) is a medicinal herb that has anti-inflammatory properties. It has been reported that ginger shows anti-addictive effects against chronic usage of morphine; however, its influence on morphine-induced neuroinflammation has not yet been clarified. METHODS: Morphine (12 mg/kg) was administrated intraperitoneally for 6 consecutive days. To evaluate the effect of ginger on morphine-induced neuroinflammation, ginger extract (100 mg/kg) was given orally 30 minutes before morphine. Glial fibrillary acidic protein (GFAP) and p38 mitogen-activated protein kinase (p38 MAPK) levels were assayed by immunoblotting in the rat nucleus accumbens (NAcc). FINDINGS: The injection of chronic morphine increased the levels of proteins involved in neuroinflammation (p38 MAPK and GFAP) in NAcc. Furthermore, the levels of p38 MAPK and GFAP significantly returned to the control levels by ginger extract. CONCLUSION: The results suggest that the ginger extract can reduce morphine-induced neuroinflammation in NAcc.

Extracellular calcium influx through L-type calcium channels, intracellular calcium currents and extracellular signal-regulated kinase signaling are involved in the abscisic acid-induced precognitive and anti-anxiety effects.

Abscisic acid (ABA), a critical phytohormone, is also produced in animal tissues. It has been reported that ABA has pro-cognitive and anti-anxiety effects in rats. However, its detailed mechanism has not yet been clarified. Here, the possible roles of extracellular and intracellular calcium store and ERK signaling were evaluated in pro-cognitive and anti-anxiety effects of ABA. Morris water maze (MWM) and plus maze tests were used to evaluate the learning and memory and anxiety-like behavior, respectively, in rats. The inhibitors of L- (nifedipine) and T-type (amiloride) calcium channels and endoplasmic reticulum Ca2+-ATPase (thapsigargin) were centrally (i.c.v.) injected 15 min before ABA. Hippocampal and prefrontal lobe levels of phosphorylated extracellular signal-regulated Kinase (p-ERK) were assessed by immunoblotting. The data showed that ABA has promoting effect on rat's performance in MWM task and induced anti-anxiety effect. In addition, nifedipine and thapsigargin significantly prevented while, amiloride had no effect on the mentioned effects of ABA. Furthermore, p-ERK levels were significantly increased in ABA-treated rats which were inhibited by nifedipine and thapsigargin pretreatment. It seems that the extracellular calcium influx through L-type calcium channels, intracellular calcium storage and ERK signaling are involved, at least in part, in the pro-cognitive and anti-anxiety effects of ABA.

Intranasal insulin activates Akt2 signaling pathway in the hippocampus of wild-type but not in APP/PS1 Alzheimer model mice.

Type 2 diabetes mellitus (T2DM) increases the risk for Alzheimer's disease (AD). Human AD brains show reduced glucose metabolism as measured by [18F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET). Here, we used 14-month-old wild-type (WT) and APPSwe/PS1dE9 (APP/PS1) transgenic mice to investigate how a single dose of intranasal insulin modulates brain glucose metabolism using FDG-PET and affects spatial learning and memory. We also assessed how insulin influences the activity of Akt1 and Akt2 kinases, the expression of glial and neuronal markers, and autophagy in the hippocampus. Intranasal insulin moderately increased glucose metabolism and specifically activated Akt2 and its downstream signaling in the hippocampus of WT, but not APP/PS1 mice. Furthermore, insulin differentially affected the expression of homeostatic microglia markers P2ry12 and Cx3cr1 and autophagy in the hippocampus of WT and APP/PS1 mice. We found no evidence that a single dose of intranasal insulin improves overnight memory. Our results suggest that intranasal insulin exerts diverse effects on Akt2 signaling, autophagy, and the homeostatic status of microglia depending on the degree of AD-related pathology.

Phosphatidylinositol-3-kinase and protein kinase C are involved in the pro-cognitive and anti-anxiety effects of phytohormone abscisic acid in rats.

The phytohormone abscisic acid (ABA) exists in animal tissues particularly in the brain. However, the neurophysiological effects of ABA have not yet been fully determined. Signaling molecules such as PKC and PI3K have been implicated in anxiety-like behavior as well as learning and memory processes. Recently, it has been demonstrated that PKC and PI3K signaling pathways participate in some biological effects of ABA. This study was designed to evaluate the effects of central injection of ABA on spatial learning and memory and anxiety-like behavior and determine its possible signaling mechanisms. Spatial learning and memory and anxiety-like behaviors were determined using Morris water maze (MWM) and plus maze tests, respectively. ABA alone or in accompanied with selective inhibitors of PKC (chelerythrine) and PI3K (LY2940029) was injected bilaterally into the cerebral lateral ventricles. The results indicated that ABA (10µg/rat) significantly improved rats' performance in MWM which was blocked by PKC or PI3K inhibitors. In addition, ABA showed anti-anxiety effect in plus maze test, which was not observed in PKC or PI3K inhibitor-treated rats. Overall, the results indicated that ABA has positive effect on spatial learning and memory performance and elicits anti-anxiety effects which are performed, at least in part, through PI3K/PKC signaling pathway.