Effects of Dexmedetomidine on the Behavioral Outcomes in Streptozotocin‐Induced Alzheimer's Disease Rats

Empagliflozin alleviates diabetes-induced cognitive impairments by lowering nicotinamide adenine dinucleotide phosphate oxidase-4 expression and potentiating the antioxidant defense system in brain tissue of diabetic rats

Increased serum insulin levels and reduced peripheral insulin activities seen in insulin resistance syndrome are associated with age-dependent cognitive impairment and Sporadic Alzheimer's Disease (SAD), suggesting a disturbance in the insulin signalling system in the brain and possibly being one of the causes of dementia. Therefore, the streptozotocin (STZ)-induced animal may be an appropriate model for the investigation of SAD and related dementia. This study was designed to investigate the beneficial effect of Curcumin (CUR), a neuroprotective agent, on intracerebroventricular (ICV) STZ-induced cognitive impairment in rats. For this purpose, adult male Wistar rats were bilaterally ICV injected with STZ (3 mg/kg). An artificial cerebrospinal fluid (aCSF) was given to the control group (SHAM) instead of STZ on days 1 and 3. Learning and memory performance were assessed using the "passive avoidance task" and the "Morris water maze test". After confirmation of acquisition impairment with these tests, the STZ group was divided into two subgroups: STZ + vehicle (Vh) and STZ + CUR. The rats in the SHAM and STZ + Vh groups were administered intraperitoneally with 0.5 ml Vh and the rats in the STZ + CUR group were treated intraperitoneally with CUR (300 mg kg(-1) day(-1) in Vh) for 10 days starting from the 25th day after STZ injection. The Morris water maze test was reapplied on the 35th day after STZ injection and all of the rats were sacrificed on day 36 for quantitation of IGF-1 and for histopathological evaluation. Rats in the STZ + CUR group were found to have a higher performance in cognitive tests than rats in the STZ + Vh group (P < 0.01). In parallel with the cognitive tests, IGF-1 levels were decreased in all of the STZ-injected groups (1.78 +/- 0.34) compared to the SHAM group (3.46 +/- 0.41). In contrast, CUR treatment significantly increased IGF-1 levels (P < 0.001). The degree of neuronal loss decreased after CUR treatment compared to the SHAM group (P < 0.02). These results clearly indicate that CUR treatment is effective in reducing the cognitive impairment caused by STZ in rats, and may be a potential therapeutic agent for altering neurodegeneration in SAD.

Background: Learning and memory may decline due to Alzheimer’s disease (AD) in older adults. A reduction in cyclic guanosine monophosphate concentration and an increase in phosphodiesterase activity have been reported in the process of aging. Although phosphodiesterase (PDE) type 5 inhibitor, Tadalafil is used to treat erectile dysfunction; PDE inhibitors possibly prevent cognition impairment in aging. This study was designed to investigate the effects of tadalafil on memory in middle-aged and young healthy and AD rats. Methods: Memory impairment was induced by intracerebroventricular (ICV) administration of streptozotocin (STZ; 3 mg/kg) in AD rats. Male Wistar rats (middle-aged and young) were distributed into six groups as follows: two control, two AD, and two AD+tadalafil (1 mg/kg) groups. Saline or tadalafil was administered once a day orally for 40 consecutive days. Animals were tested using novel object recognition (NOR), passive avoidance learning (PAL), and Morris water maze (MWM) tests. Results: Aged AD rats exhibited a significant impairment in cognition in the NOR test and impaired learning and memory in PAL and MWM tests compared with the control aged rats. Tadalafil treatment in aged AD rats significantly improved the discrimination index in the NOR test, decreased the time spent in the dark compartment in the PAL test, and increased time spent in the target quadrant in MWM tests compared with aged AD rats. In young AD rats, treatment with tadalafil significantly enhanced cognition, learning, and memory in the NOR, PAL, and MWM tests compared with young AD rats treated with saline. Conclusion: Tadalafil treatment in aged rats improves cognition and memory after STZ-induced (ICV) memory impairment. It can be concluded that chronic treatment with tadalafil is protective against cognitive, learning, and memory impairment in both young and aged subjects.

Assessment of ultrasonic vocalization-mediated communication deficits in AD rats: A social learning paradigm using conspecific drinking behavior.

Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping

Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats

Objective To observe the effect of fluoxetine on the single prolonged stress model which mimic the post-traumatic stress disorder (PTSD). Methods Rats receiving single prolonged stress (SPS) (2 h restraint + 20 min FST + anaesthesized to lose consciousness with ethylether) or not were given fluoxetine or tap water for 15 days. Elevated plus maze(EPM),open-field test(OF) and morris water maze(MWM) tests were used to evaluate rats' fear response to environment,high alertness,anxiety & depression behavior,and learning and memory ability. Results In open field test, group of fluoxetine(F1 (8895. 85 ± 599. 78) mm, (40. 23 ±4. 32) s;F2 (8654.07 ±866.05)mm,(41.57 ±4.34)s, P<0.05) showed significant increase in activity times and horizontal motion distance compared with group of SPS (4678.85 ±495.33)mm, (22.15 ±3.43)s, P<0.05). In EPM experiment,group of fluoxetine(F1 (32. 62 ± 4. 57)% , (17. 58 ± 3. 23)% ; F2 (39. 75 ± 4. 46)% , (19. 74 ± 4.44) %) showed significant increase in percentage of the open-arm into the maze and percentage of the open arm pause compared with group of SPS ((23.67 ±2. 87)% ,(12.46 ±2.55)% , P<0.05). In MWM experiment,the escape latency of the SPS group increased significantly in comparison to that in sham group (P<0.01) and fluoxetine group. Fluoxetine significantly reversed the SPS-induced decrease in time spent in the target quadrant (P< 0.05). Conclusion Added fluoxetine can obviously improve rats' fear response to environment ,high alertness ,anxiety & depression behavior as well as learning and memory ability. Key words: Fluoxetine; Post-traumatic stress disorder; Open-field test; Elevated plus maze

Nitric oxide impairs spatial learning and memory in a rat model of Alzheimer’s disease via disturbance of glutamate response in the hippocampal dentate gyrus during spatial learning

Effects of systemic Thalidomide and intracerebroventricular Etanercept and Infliximab administration in a Streptozotocin induced dementia model in rats

Environmental enrichment enhances the antidepressant effect of ketamine and ameliorates spatial memory deficits in adult rats

Grewia asiatica L. fruit natively called phalsa is a popular berry of Pakistan and widely consumed in the form of fresh juices and carbonated drinks in the summer season. The berry is enriched with antioxidants such as phenols, flavonoids, anthocyanins, and vitamin C. Scientifically, it is the least explored berry in terms of neuromodulatory activities, and therefore, in the designed study, chronically fed rats with the different dilutions (5%−30%) of fruit juice were subjected to behavioral assessment for anxiety, depression, and cognition (spatial memory) followed by biochemical analysis of isolated brains. Results revealed a prominent impact of 20 and 30% dilutions of fruit exudate as treated animals showed anxiolytic behavior to central zone (P < 0.05) of open field test (OFT) and open arms of elevated plus maze (EPM) (P < 0.05) in anxiety models. Overall, immobility of rats treated with a higher concentration of exudate in forced swim test (FST) was reduced (P < 0.05) presenting antidepressant-like activity. Moreover, in learning and memory experimental models, the treated animals reversed scopolamine-induced amnesic effects as evident from improved step-through latencies (P < 0.05 vs. scopolamine; passive avoidance test), spontaneous alternation behavior (P < 0.05 vs. scopolamine; Y-maze test), discrimination index (P < 0.05 vs. scopolamine; novel object recognition test), and escape latencies (P < 0.05 vs. scopolamine; Morris water maze). Biochemical studies of isolated brains from treated rats demonstrated significantly elevated levels of superoxide dismutase and glutathione peroxidase (P < 0.05), whereas levels of acetylcholinesterase and malondialdehyde level (P < 0.05) were reduced, indicating its potential to reduce oxidative damage in the brain and modulation with the cholinergic system. The outcomes of studies support the benefits of phytoconstituents possessed by G. asiatica fruit in the amelioration of neurological disorders that could be due to their antioxidative capacity or due to interaction with GABAergic, serotonergic, and cholinergic systems in the brain.

Low-dose lithium mono- and adjunctive therapies improve MK-801-induced cognitive impairment and schizophrenia-like behavior in mice - Evidence from altered prefrontal lobe Ca2+ activity

Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a decrement in the number of synapses, an increment in the production of oxygen free radicals and inflammatory cytokines. Green tea (GT) plays a defensive performance in different neurodegenerative conditions, such as cognition deficit. This study investigated the neuroprotective effect of green tea (GT) on cognitive disorder, inflammation, and oxidative stress in the streptozotocin (STZ)- induced AD model. Materials and Methods The rats were divided into four groups: (1) Control, (2) GT, (3) Alz, and (4) GT + Alz. AD was induced by the injection of STZ (3 mg/kg, bilaterally, ICV). Morris water maze and passive avoidance tests were done to evaluate the memory and learning of rats. Biochemical parameters were measured with specialized ELISA kits. Results Briefly, data analysis revealed that GT administration for 21 days improved memory impairment induced by the injection of STZ. Pretreatment with GT enhanced time spent in the goal quarter and reduced latency time and path length. Furthermore, pretreatment with GT prevented the increment of malondialdehyde (MDA) concentration in STZ-treated rats. As a pro-inflammatory cytokine, tumor necrosis factor- α (TNF-α) concentration was suppressed with the GT pretreatment. Total antioxidant capacity was increased after GT administration in rats treated compared with AD rats. Conclusions GT pretreatment attenuated STZ-induced learning and memory impairment through the suppression of TNF-α and MDA concentrations. The beneficial effects of GT on memory could be attributed to its protective effects on oxidative defenses.

Background: Toxoplasma gondii is a neurotropic parasite with lifelong persistence in the host brain. Many researchers suggested toxoplasmosis as a risk factor for the development of Alzheimer's disease (AD); however, the link between them has not been fully elucidated. Objectives: The present study was designed to investigate the effects of chronic toxoplasmosis infection with Types I (RH), II (PRU), and III (VEG) strains alone and in combination on cognitive impairments in Alzheimer's rat model. Methods: Seven months after the inoculation of the strains, AD was induced bilaterally in rats by injecting human amyloid beta 1-42 (Aβ1-42) peptide into the brain hippocampus. Behavioral tests, including the elevated plus maze (EPM) and Morris water maze (MWM) were conducted 10 days after the AD induction. Results: Our findings showed that chronic infection with RH strain increased anxiety-like behavior in the Alzheimer's rats in the EPM. In agreement with EPM findings, rats infected with the RH strain exacerbated spatial learning disorders in the MWM test; however, it did not affect the spatial memory. Conversely, infection with the PRU strain significantly enhanced spatial learning without being able to improve memory impairments in the Alzheimer's rat model. Improvement in spatial learning and memory impairments were also observed in rats infected with PRU and VEG strains in combination. Conclusions: Taken together, our findings suggest that chronic infection with PRU strain, as well as PRU and VEG strains in combination, can significantly improve cognitive deficits induced by Aβ1-42 in Alzheimer's rats, while RH strain plays a detrimental role in AD pathogenesis.

Cucurbita maxima (CM) seed oil is commonly used in Indian folk medicine to treat various ailments. We have investigated the effect of CM seed oil on memory impairment induced by scopolamine in rats. Male adult Wistar rats were administered scopolamine 1 mg/kg body weight, i.p. or 1.25 mg/kg body weight, s.c. to induce memory impairment. The nootropic agent piracetam 100 mg/kg body weight, i.p. and CM seed oil 100 and 200 mg/kg body weight, p.o. were administered daily for five consecutive days. The memory function was evaluated in the Morris water maze (MWM) test, the social recognition test (SRT), the elevated plus maze (EPM) test, and the pole climbing test (PCT). Acetylcholinesterase (AChE) activity and oxidative stress parameters were estimated in the cortex, hippocampus, and cerebellum of the brains after completion of the behavioural studies. The effects of scopolamine on the levels of the tumour necrosis factor alpha (TNF-α) transcript were also investigated. Scopolamine caused memory impairment in all the behavioural paradigms along with a significant increase in the AChE activity and oxidative stress in the brain. Scopolamine also caused a significant increase in the expression of TNF-α in the hippocampus. CM seed oil exhibited antiamnesic activity as indicated by a significant reduction in the latency time in the MWM test and decreased social interaction during trial 2 in the SRT. Further, treatment with CM seed oil significantly decreased the AChE activity and malondialdehyde levels and increased the glutathione level in brain regions. CM seed oil also significantly decreased the expression of TNF-α in the hippocampus. The effect of CM seed oil on behavioural and biochemical parameters was comparable to that observed in rats treated with piracetam. These results indicate that CM seed oil may exert antiamnesic activity which may be attributed to the inhibition of AChE and inflammation as well as its antioxidant activity in the brain.