Strain differences in activity and emotionality do not account for differences in learning and memory performance between C57BL/6 and DBA/2 mice

This study examined emotionality, activity, learning and memory, as well as the influence of emotionality and activity on learning and memory performance in C57BL/6 and DBA/2 mice using a mouse-test battery. DBA/2 mice performed more poorly than C57BL/6 mice in complex learning tasks such as the water maze and object recognition tasks. In contrast, C57BL/6 mice showed attenuated habituation to novelty in the open field apparatus and poorer performance in the step-down passive avoidance task. The C57BL/6 mice were less exploratory and more anxious than the DBA/2 mice. The anxiety score (open arm entries in the elevated plus maze) was significantly correlated with all measures of learning and memory in the object recognition task, and some measures in the passive avoidance and water maze tasks. Analysis of covariance (with open arm entries as a covariate) revealed that some measures on trial 1 of the object recognition task, but not the memory scores on trial 2, were confounded by anxiety. No confounding factors of anxiety were found in the water maze or passive avoidance tasks. Similar results were obtained with the activity scores (line crossing and rearing in the open field). In conclusion, strain differences in activity and anxiety did not account for strain differences in learning and memory performance of C57BL/6 and DBA/2 mice. Nonetheless, the importance of using complete behavioural test batteries should be stressed to ensure that strain differences in learning and memory tasks are not confounded by non-cognitive factors.     

Impaired striatum-dependent behavior in GASP-1-knock-out mice

G protein-coupled receptor (GPCR) associated sorting protein-1 (GASP-1) is suspected to play a key role in recycling and degradation of several GPCRs. In a previous study, we have shown that GASP-1-knock-out (GASP-1-KO) mice displayed deficits in acquiring a cocaine self-administration task, associated with an exacerbated down-regulation of striatal dopaminergic and cholinergic receptors. Among several possibilities, GASP-1 deficiency could have impaired memory processes underlying the acquisition of the operant conditioning task. Therefore, the present study investigated cognitive performances of GASP-1-KO mice and their wild-type littermates (WT) in a broad variety of memory tasks. Consistent with a deficit in procedural memory, GASP-1-KO mice showed delayed acquisition of a food-reinforced bar-press task. During water-maze training in hidden- or visible-platform paradigms, mutant and WT mice acquired the tasks at the same rate. However, GASP-1 mice exhibited persistent thigmotaxic swimming, longer distance to the platform, and reduced swim speed. There was no deficit in several tasks requiring simple behavioral responses (Barnes maze, object recognition and passive avoidance tasks). Thus, the ability to acquire and/or express complex responses seems affected in GASP-1-deficient mice. Hippocampal functions were preserved, as the retention of an acquired memory in spatial tasks remained unaffected. The pattern of behavioral deficits observed in GASP-1-KO mice is coherent with current knowledge on the role of striatal GPCRs in acquisition/expression of skilled behavior and in motivation. Together with the previous findings, the so far established phenotype of GASP-1-KO mice makes them a potentially exciting tool to study striatal functions.     

Exposure to Folate Receptor Alpha Antibodies during Gestation and Weaning Leads to Severe Behavioral Deficits in Rats: A Pilot Study

The central nervous system continues to develop during gestation and after birth, and folate is an essential nutrient in this process. Folate deficiency and folate receptor alpha autoantibodies (FRα-AuAb) have been associated with pregnancy-related complications and neurodevelopmental disorders. In this pilot study, we investigated the effect of exposure to FRα antibodies (Ab) during gestation (GST), the pre-weaning (PRW), and the post weaning (POW) periods on learning and behavior in adulthood in a rat model. In the open field test and novel object recognition task, which examine locomotor activity and anxiety-like behavior, deficits in rats exposed to Ab during gestation and pre-weaning (GST+PRW) included more time spent in the periphery or corner areas, less time in the central area, frequent self-grooming akin to stereotypy, and longer time to explore a novel object compared to a control group; these are all indicative of increased levels of anxiety. In the place avoidance tasks that assess learning and spatial memory formation, only 30% of GST+PRW rats were able to learn the passive place avoidance task. None of these rats learned the active place avoidance task indicating severe learning deficits and cognitive impairment. Similar but less severe deficits were observed in rats exposed to Ab during GST alone or only during the PRW period, suggesting the extreme sensitivity of the fetal as well as the neonatal rat brain to the deleterious effects of exposure to Ab during this period. Behavioral deficits were not seen in rats exposed to antibody post weaning. These observations have implications in the pathology of FRα-AuAb associated with neural tube defect pregnancy, preterm birth and neurodevelopmental disorders including autism.     

Motor-Coordination-Dependent Learning,More than Others,Is Impaired in Transgenic Mice Expressing Pseudorabies Virus Immediate-Early Protein IE180

The cerebellum in transgenic mice expressing pseudorabies virus immediate-early protein IE180 (TgIE96) was substantially diminished in size, and its histoarchitecture was severely disorganized, resulting in severe ataxia. TgIE96 mice can therefore be used as an experimental model to study the involvement of cerebellar circuits in different learning tasks. The performance of three-month-old TgIE96 mice was studied in various behavioral tests, including associative learning (classical eyeblink conditioning), object recognition, spatial orientation (water maze), startle response and prepulse inhibition, and passive avoidance, and compared with that of wild-type mice. Wild-type and TgIE96 mice presented similar reflexively evoked eyeblinks, and acquired classical conditioned eyelid responses with similar learning curves for both trace and delay conditioning paradigms. The two groups of mice also had similar performances during the object recognition test. However, they showed significant differences for the other three tests included in this study. Although both groups of animals were capable of swimming, TgIE96 mice failed to learn the water maze task during the allowed time. The startle response to a severe tone was similar in both control and TgIE96 mice, but the latter were unable to produce a significant prepulse inhibition. TgIE96 mice also presented evident deficits for the proper accomplishment of a passive avoidance test. These results suggest that the cerebellum is not indispensable for the performance of classical eyeblink conditioning and for object recognition tasks, but seems to be necessary for the proper performance of water maze, prepulse inhibition, and passive avoidance tests.     

Prostaglandin E2 EP1 Receptor Antagonist Improves Motor Deficits and Rescues Memory Decline in R6/1 Mouse Model of Huntington's Disease

In this study, we evaluated the potential beneficial effects of antagonizing prostaglandin E2 (PGE2) EP1 receptor on motor and memory deficits in Huntington's disease (HD). To this aim, we implanted an osmotic mini-pump system to chronically administrate an EP1 receptor antagonist (SC-51089) in the R6/1 mouse model of HD, from 13 to 18 weeks of age, and used different paradigms to assess motor and memory function. SC-51089 administration ameliorated motor coordination and balance dysfunction in R6/1 mice as analyzed by rotarod, balance beam, and vertical pole tasks. Long-term memory deficit was also rescued after EP1 receptor antagonism as assessed by the T-maze spontaneous alternation and the novel object recognition tests. Additionally, treatment with SC-51089 improved the expression of specific synaptic markers and reduced the number of huntingtin nuclear inclusions in the striatum and hippocampus of 18-week-old R6/1 mice. Moreover, electrophysiological studies showed that hippocampal long-term potentiation was significantly recovered in R6/1 mice after EP1 receptor antagonism. Altogether, these results show that the antagonism of PGE2 EP1 receptor has a strong therapeutic effect on R6/1 mice and point out a new therapeutic candidate to treat motor and memory deficits in HD.     

Reversal of Aging and Chronic Ethanol-induced Cognitive Dysfunction by Quercetin a Bioflavonoid

Cognitive dysfunction, one of the most striking age-related impairments seen in human beings, has been correlated to the vulnerability of the brain to increased oxidative stress during aging process. Quercetin is a bioflavonoid with strong antioxidant properties. Experiments were performed to study the possible effects of quercetin on cognitive performance of young, aged or ethanol-intoxicated mice (an animal model for cognition dysfunction) using one trail step down type of passive avoidance and elevated plus maze tasks, respectively. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance and in elevated plus-maze task. Chronic administration of quercetin (10, 25 and 50 mg/kg) for 30 days or its co-administration with ethanol (15% w/v, 2 g/kg per orally) for 24 days significantly reversed the age-related or chronic ethanol-induced retention deficits in both the test paradigms. However, in both memory paradigms chronic administration of quercetin failed to modulate the retention performance of young mice. Chronic quercetin administration for 30 days also reversed age associated increase in TBARS levels and decline in forebrain total glutathione (GSH), SOD and catalase levels. Chronic ethanol administration to young mice produced an increase in lipid peroxidation, and a decline in forebrain total glutathione (GSH), SOD and catalase levels, which was significantly reversed by the co-administration of quercetin (10, 25 and 50 mg/kg). The results of the present study showed that chronic quercetin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.     

Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid

Cognitive dysfunction, one of the most striking age-related impairments seen in human beings, has been correlated to the vulnerability of the brain to increased oxidative stress during aging process. Quercetin is a bioflavonoid with strong antioxidant properties. Experiments were performed to study the possible effects of quercetin on cognitive performance of young, aged or ethanol-intoxicated mice (an animal model for cognition dysfunction) using one trail step down type of passive avoidance and elevated plus maze tasks, respectively. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance and in elevated plus-maze task. Chronic administration of quercetin (10, 25 and 50 mg/kg) for 30 days or its co-administration with ethanol (15% w/v, 2 g/kg per orally) for 24 days significantly reversed the age-related or chronic ethanol-induced retention deficits in both the test paradigms. However, in both memory paradigms chronic administration of quercetin failed to modulate the retention performance of young mice. Chronic quercetin administration for 30 days also reversed age associated increase in TBARS levels and decline in forebrain total glutathione (GSH), SOD and catalase levels. Chronic ethanol administration to young mice produced an increase in lipid peroxidation, and a decline in forebrain total glutathione (GSH), SOD and catalase levels, which was significantly reversed by the co-administration of quercetin (10, 25 and 50 mg/kg). The results of the present study showed that chronic quercetin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.     

Possible antioxidant mechanism in melatonin reversal of aging and chronic ethanol-induced amnesia in plus-maze and passive avoidance memory tasks

Cognitive dysfunction is one of the most striking age-related impairments seen in human beings and animals. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. Pineal hormone melatonin is reported to be an endogenous antioxidant, whose peak plasma level declines during aging and in Alzheimer's disease (AD). Present experiments were performed to study the possible effect of exogenously administered melatonin on cognitive performance of young, aged, or ethanol-intoxicated mice (an animal model for AD) using one trial step-down type of passive avoidance and elevated plus-maze task. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance and in elevated plus-maze task. Chronic administration of melatonin (0.1-10 mg/kg, sc) for 30 d or its coadministration with ethanol (15% W/V, 2 g/kg perorally) for 24 d significantly reversed the age-induced or chronic ethanol-induced retention deficits in both the test paradigms. However, in both the memory paradigms chronic administration of melatonin failed to modulate the retention performance of young mice. Chronic administration of melatonin (0.1-10 mg/kg) for 30 d also reversed age-associated decline in forebrain total glutathione (tGSH) level. Chronic ethanol administration to young mice produced decline in forebrain tGSH level and enhanced brain lipid peroxidation, which was significantly reversed by coadministration of melatonin (10 mg/kg). The results of this study showed chronic melatonin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.     

Reproduction of passive avoidance reactions after neurotensin microinjection into nucleus accumbens of rat brain against the background of reserpine action

The purpose of the study was to reveal the features of the influence of neurotensin injected into the nucleus accumbens on behaviour of rats after systemic administration of reserpine in the dose of 2 mg/kg. Reprodution of passive avoidance conditioned reactions, painful stimulation aftereffects on locomotor activity in the "open field", and behavior in the elevated plus-maze were studied. It was shown that reserpine administration impaired the reproduction of passive avoidance reactions and weakened the oppressing aftereffect of painful stimulation, which can be due to a decrease in anxiety in rats. Neurotensin prevented disorders in the defensive behavior evoked by reserpine and intensified the state of anxiety in the elevated plus-maze. The positive influence ofneurotensin on the reproduction of passive avoidance can be associated with the recovery of the anxiogenic effect of painful stimulation destroyed by reserpine. Thus, neurotensin injected into the nucleus accumbens could normalize the balance of brain monoaminergic systems.     

Pretreatment with caerulein protects against memory impairment induced by protein kinase C inhibitors in the rat.

The effect of subcutaneously injected caerulein (CER) on memory impairment induced by protein kinase C (PKC) inhibitors, H-7 and melittin, was examined in rats. Intracerebroventricular injection of PKC inhibitors caused marked memory impairment in one-trial passive avoidance response and Morris water tank tasks. However, when rats were pretreated with CER at a subcutaneous dose of 1 microgram/kg 3 hours before the training trials, the reduced latency of the passive avoidance response was significantly increased, and in the Morris water pool tasks the memory deficit induced by PKC inhibitors completely disappeared. These results indicate that CER can offer protection against the effect of PKC inhibitors at least from the viewpoint of the memory processes.     

ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, significantly improved scopolamine-induced memory impairment in mice

We assessed the effects of oral treatments of ESP-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, on learning and memory deficit. The cognition-enhancing effect of ESP-102 was investigated in scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and Morris water maze performance tests. Acute oral treatment (single administration prior to scopolamine treatment) of mice with ESP-102 (doses in the range of 10 to 100 mg/kg body weight) significantly reduced scopolamine-induced memory deficits in the passive avoidance performance test. Another noteworthy result included the fact that prolonged oral daily treatments of mice with much lower amounts of ESP-102 (1 and 10 mg/kg body weight) for ten days reversed scopolamine-induced memory deficits. In the Morris water maze performance test, both acute and prolonged oral treatments with ESP-102 (single administration of 100 mg/kg body weight or prolonged daily administration of 1 and 10 mg/kg body weight for ten days, respectively, significantly ameliorated scopolamine-induced memory deficits as indicated by the formation of long-term and/or short-term spatial memory. In addition, we investigated the effects of ESP-102 on neurotoxicity induced by amyloid-beta peptide (Abeta25-35) or glutamate in primary cultured cortical neurons of rats. Pretreatment of cultures with ESP-102 (0.001, 0.01 and 0.1 mug/ml) significantly protected neurons from neurotoxicity induced by either glutamate or Abeta25-35. These results suggest that ESP-102 may have some protective characteristics against neuronal cell death and cognitive impairments often observed in Alzheimer's disease, stroke, ischemic injury and other neurodegenerative diseases.     

NCAM deficiency in the mouse forebrain impairs innate and learned avoidance behaviours

The neural cell adhesion molecule (NCAM) has been implicated in the development and plasticity of neural circuits and the control of hippocampus‐ and amygdala‐dependent learning and behaviour. Previous studies in constitutive NCAM null mutants identified emotional behaviour deficits related to disturbances of hippocampal and amygdala functions. Here, we studied these behaviours in mice conditionally deficient in NCAM in the postmigratory forebrain neurons. We report deficits in both innate and learned avoidance behaviours, as observed in elevated plus maze and passive avoidance tasks. In contrast, general locomotor activity, trait anxiety or neophobia were unaffected by the mutation. Altered avoidance behaviour of the conditional NCAM mutants was associated with a deficit in serotonergic signalling, as indicated by their reduced responsiveness to (±)‐8‐hydroxy‐2‐(dipropylamino)‐tetralin‐induced hypo-thermia. Another serotonin‐dependent behaviour, namely intermale aggression that is massively increased in constitutively NCAM‐deficient mice, was not affected in the forebrain‐specific mutants. Our data suggest that genetically or environmentally induced changes of NCAM expression in the late postnatal and mature forebrain determine avoidance behaviour and serotonin (5‐HT)_1A receptor signalling.     

Effects of orexin-A on memory processing

Orexin-A is an endogenous peptide with receptors present throughout the brain. Here, we examined the effect of post-training administration of orexin-A on retention in active and passive avoidance. Orexin-A administered by intracerebroventricular (i.c.v.) injection to CD-1 mice post-training improved retention in both T-maze footshock avoidance and one trial step-down passive avoidance. SAMP8 mice have age-related deficits in learning and memory, which correlate with an increase in brain levels of beta amyloid (Abeta) and an impaired response to memory-enhancing compounds. Orexin-A at 3nmol improved retention in young and old SAMP8 mice. These findings show that orexin-A can improve memory even with overproduction of Abeta.     

Melatonin Attenuates Scopolamine-Induced Memory/Synaptic Disorder by Rescuing EPACs/miR-124/Egr1 Pathway

Alzheimer’s disease (AD) is the most prevalent type of dementia in elderly people. There are decreased melatonin levels in the serum of AD patients, and melatonin supplements are able to reverse AD pathology and memory deficits in many animal experiments and clinical trials. However, the underlying mechanism regarding how melatonin rescues the AD-like memory/synaptic disorder remains unknown. Here, we use the Morris water maze, step-down inhibitory avoidance task, in vivo long-term potentiation recording, and Golgi staining and report that intraperitoneal injection of melatonin (1 mg/kg/day) for 14 days in rats effectively reverses the memory and synaptic impairment in scopolamine-induced amnesia, a well-recognized dementia animal model. Using real-time polymerase chain reaction and western blotting experiments, we further determined that melatonin rescues the EPACs/miR-124/Egr1 signal pathway, which is important in learning and memory, as reported recently. Our studies provide a novel underlying epigenetic mechanism for melatonin to attenuate the synaptic disorder and could benefit drug discovery in neurodegenerative diseases.     

Aluminum-Induced Cholinergic Deficits in Different Brain Parts and Its Implications on Sociability and Cognitive Functions in Mouse

Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer’s disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl₃ (250 mg/kg). Acetylcholine level, free choline level, and choline acetyltransferase gene expression were determined in cortex, hippocampus, and amygdala. The mice were subjected to behavior tests (novel object recognition and social novelty preference) to assess memory deficits. The acetylcholine level in cortex and hippocampus was significantly reduced in aluminum-treated animals, as compared to cortex and hippocampus of control animals. Acetylcholine level in amygdala of aluminum-treated animals remained unchanged. Free choline level in all the three brain parts was found unaltered in aluminum-treated mice. The novel object recognition memory was severely impaired in aluminum-treated mice, as compared to the control group. Similarly, animals treated with aluminum showed reduced sociability compared to the control mice group. Our study demonstrates that aluminum exposure via drinking water causes reduced acetylcholine synthesis in spite of normal free choline availability. This deficit is caused by reduced recycling of acetylcholine due to lower choline acetyltransferase level. This cholinergic hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the most affected brain part after aluminum intoxication.     

(−)-Linalool, a naturally occurring monoterpene compound, impairs memory acquisition in the object recognition task, inhibitory avoidance test and habituation to a novel environment in rats

It is known that (−)-linalool is a competitive antagonist of NMDA receptors, which play a key role in the learning and memory processes; however, only a few studies have reported a possible interference of (−)-linalool in memory. The purpose of this study was to investigate the (−)-linalool effects on acquisition of short- and long-term memories through the objects recognition task, inhibitory avoidance test and habituation to a novel environment. Furthermore, the open field test was used to investigate the interference of (−)-linalool in motivation, locomotion and exploration by animals. Wistar male adult rats received an intraperitoneal injection (i.p.) of saline (NaCl 0.9%), tween 5% or (−)-linalool (50 or 100 mg/kg) before training in the tasks; MK-801 (0.1 mg/kg), a glutamate antagonist, was used as positive control. Short-term (STM) and long-term (LTM) memories were tested 1.5 and 24 h after training, respectively, in the inhibitory avoidance and recognition objects. The results suggested that (−)-linalool (as 50- and 100-mg/kg doses) impaired LTM acquisition, but not STM acquisition, in the object recognition task. In the inhibitory avoidance test, animals receiving linalool (both doses) showed impairment in acquisition of both memories measured. In the open field test, the animals that received (−)-linalool showed no significant difference in the crossings and latency to start the locomotion in any of the doses tested, although (−)-linalool 100 mg/kg reduced rearing behavior. When re-exposed to open field 24 h after training, the rats that received (−)-linalool 100 mg/kg showed no habituation. Taken together, these data suggested that (−)-linalool was able to impair the acquisition of memory in rats, which can be associated to (−)-linalool antagonist capacity as regards NMDA glutamatergic receptors, since other glutamate antagonists also seem to affect memory.     

Prefrontal cortex aspiration in pups and juvenile rats: behavioural changes and recovery of function

Male Wistar rats sustaining prefrontal cortex aspiration or sham operation at 6 days or 30 days of age were submitted to the following behavioural tests: open-field, acquisition and retention of two-way active as well as passive avoidance tasks. In the open-field the locomotor activity proved enhanced in all the aspirated animals and this enhancement lasted for 30 days. In the two-day active avoidance task, an acquisition deficit was observed in both aspirated groups; but when retrained one month later, they were able to acquire the avoidance task like sham-operated rats and no difference appeared between the groups aspirated at 6 or at 30 days of age. Concerning the passive avoidance task, no difference could be detected between aspirated and sham-operated animals of both groups except that the rats aspirated at an early age (6 days) seemed to display a better avoidance ability in the retention test. These behavioural alterations (hyperactivity and impairment of the acquisition of the 2-way active avoidance) resulted from the prefrontal cortex aspiration, at whatever age this aspiration was performed (6 days or 30 days). They disappeared after a postoperative recovery period of about one month, as evidenced by this longitudinal study.     

Bisphenol A Does Not Affect Memory Performance in Adult Male Rats

Bisphenol A (BPA) is an estrogenic endocrine disruptor used for producing polycarbonate plastics and epoxy resins. This study investigated the effects of oral BPA administration on memory performance, general activity, and emotionality in adult male Sprague Dawley rats using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) used to assess spatial memory performance. In addition, in order to confirm the effects of BPA on spatial memory performance, we examined whether intrahippocampal injection of BPA affects spatial memory consolidation. In the MAZE test, although oral BPA administration at 10 mg/kg significantly altered the number of entries into the incorrect area compared to those of vehicle-treated rats, male rats given BPA through either oral administration or intrahippocampal injection failed to show significant differences in latencies to reach the reward. Also, oral BPA administration did not affect fear-motivated memory performance in the step-through passive avoidance test. Oral BPA administration at 0.05 mg/kg, the lowest dose used in this study, was correlated with a decrease in locomotor activity in the open-field test, whereas oral administration at 10 mg/kg, the highest dose used in this study, was correlated with a light anxiolytic effect in the elevated plus-maze test. The present study suggests that BPA in adulthood has little effect on spatial memory performance in male rats.     

Embelin Attenuates Intracerebroventricular Streptozotocin-Induced Behavioral,Biochemical, and Neurochemical Abnormalities in Rats

Embelin, the main active constituent of Embelia ribes, has been reported to possess various pharmacological actions, including anti-inflammatory, antioxidant, anticonvulsant, and neuroprotective. The present study was designed to investigate neuroprotective mechanisms and therapeutic potential of embelin against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic dementia in rats. STZ was infused bilaterally at the dose of (3 mg/kg/1 μl/1 min) ICV on day first and third. Spatial and non-spatial memory was evaluated using Morris water maze and object recognition task in rats. Embelin (2.5, 5, and 10 mg/kg, i.p.) was administrated for 14 days from seventh day onwards after first ICV-STZ infusion in rats. On day 22, rats were sacrificed and hippocampal brain regions were used to identify biochemical, neurochemical, and neuroinflammatory alterations. STZ-infused rats showed significant learning and memory deficit which was associated with an increase in oxidative stress (lipid peroxidation and nitrite), compromised antioxidant defense (reduced glutathione), neurotransmitter alterations (AChE, dopamine, noradrenaline, 5-hydroxytryptamine, gama amino butyric acid, and glutamate), and elevation in neuroinflammatory cytokine (IL-1 β, IL-6, and TNF-α) levels. Embelin dose dependently attenuated STZ-induced cognitive deficit and biochemical alterations and restored hippocampal neurochemical levels. The observed protective effect might be attributed to the antioxidant and anti-inflammatory potential of embelin and its ability to restore hippocampal neurochemistry. Thus, the outcomes of the current study suggest therapeutic potential of embelin in cognitive disorders such as sporadic Alzheimer’s disease (SAD).     

Effect of pyritinol, a cerebral protector, on learning and memory deficits induced by prenatal undernutrition and environmental impoverishment in young rats

The study was conducted on 64 CF strain albino rats, which were equally distributed into 8 evenly matched groups following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment--vehicle and pyritinol (100 mg/kg, ip). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/pyritinol treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for the passive avoidance learning. The results indicate that undernutrition caused significant original discrimination learning deficits whereas environmental deprivation attenuated both the original and reversal learning performance. Environmental impoverishment attenuated the retention of passive avoidance behaviour but undernutrition had no effect on this paradigm. Pyritinol treatment improved the learning and retention performance of normally reared rats and also attenuated the original and reversal learning deficits induced by parental undernutrition and postweaning environmental impoverishment. The results indicate that pyritinol may be useful in learning and memory deficits induced by malnutrition and environmental deprivation.