Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BP-induced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
Animals ; Brain ; drug effects ; metabolism ; pathology ; Cognitive Dysfunction ; drug therapy ; metabolism ; pathology ; Disease Models, Animal ; Dizocilpine Maleate ; pharmacology ; Excitatory Amino Acid Antagonists ; pharmacology ; Hydrocarbons, Brominated ; Inflammasomes ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; physiology ; Microglia ; drug effects ; metabolism ; pathology ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Neurons ; drug effects ; metabolism ; pathology ; Nootropic Agents ; pharmacology ; Random Allocation ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; metabolism ; Spatial Memory ; drug effects ; physiology ; Specific Pathogen-Free Organisms

Valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. Cell proliferation had increased to control levels at 30 and 45 d. Both markers of neurogenesis (BDNF and Notch1 levels) had returned to control levels at 45 d. These results demonstrate that memory recovery occurs over a period of six weeks after discontinuing VPA treatment and is preceded by a return of hippocampal neurogenesis to control levels.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cell Proliferation ; Cognition/drug effects* ; Dentate Gyrus/drug effects* ; Enzyme Inhibitors/pharmacology* ; Hippocampus/metabolism* ; Immunohistochemistry ; Male ; Memory Disorders/therapy* ; Memory, Short-Term/drug effects* ; Neurogenesis/drug effects* ; Neurons/metabolism* ; Rats ; Rats, Wistar ; Receptor, Notch1/metabolism* ; Spatial Memory/drug effects* ; Valproic Acid/pharmacology*

OBJECTIVETo investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain.

METHODSA total of 80 neonatal rats were randomly divided into 3 groups: sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory.

RESULTSThere was no significant difference in the survival rate of rats between the three groups (P>0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P<0.05); more than 10 days after birth, the leptin intervention group had rapid growth with higher body weight than the model and sham-operation groups (P>0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (P<0.05); from the fourth day of experiment, the leptin intervention group had a similar latency period as the sham-operation and a significantly shorter latency period than the model group (P<0.05). The results of space search experiment showed that compared with the sham-operation group, the model group had a significant reduction in the number of platform crossings and a significantly longer latency period (P<0.05); compared with the model group, the leptin intervention group had a significantly increased number of platform crossings and a significantly shortened latency period (P<0.05), while there was no significant difference between the leptin intervention and sham-operation groups.

CONCLUSIONSLeptin can alleviate spatial memory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.

Animals ; Female ; Leptin ; pharmacology ; Maze Learning ; drug effects ; Neuroprotective Agents ; pharmacology ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; Spatial Memory ; drug effects ; White Matter ; pathology

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals ; Benzothiazoles ; pharmacology ; Brain Chemistry ; drug effects ; Epilepsy ; chemically induced ; complications ; Hippocampus ; chemistry ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Histidine ; pharmacology ; Hypothalamus ; chemistry ; Kindling, Neurologic ; physiology ; Memory Disorders ; drug therapy ; etiology ; Pentylenetetrazole ; Phenoxypropanolamines ; pharmacology ; Piperidines ; pharmacology ; Pyrilamine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H2 ; drug effects ; physiology ; Spatial Memory ; drug effects ; Spectrometry, Fluorescence ; Thalamus ; chemistry

OBJECTIVETo study the effect of nano-SiO2 on spatial learning and memory.

METHODSTwenty-four male rats were randomly divided into 3 groups: control group (C group), low dose group (L group) and high dose group (H group). The rats were intragastrically administrated with nanometer particles at 25 and 100 mg/kg body weight every day for 4 weeks. After exposure, the ability of learning and memory of rats was tested by Morris water maze, and electrophysiological brain stereotactic method was used to test long-tear potentiation (LTP) in dentate gyrus (DG) of the rats.

RESULTSThe increase rate of body weight in H group was reduced significantly compared with C group ( P < 0.05). In the space exploration experiment of Morris water maze test, the escape latency of H group was longer than that of C group (P < 0.05). The rats of H group spent less time in finding the target quadrant (P < 0.05) . The rate of LP induction of H group was significantly lower than that of C group (P < 0.05). After high fre quency stimulation (HFS), The changes of amplitude of population spike (PS) of L group and H group were lower than those of C group significantly (P < 0.05, P < 0.01).

CONCLUSIONNano-SiO₂may result in impairment of spatial learning and memory ability by reducing the rate of LTP induction and the increase of PS in hippocampus.

Animals ; Dentate Gyrus ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Nanoparticles ; adverse effects ; Rats ; Silicon Dioxide ; adverse effects ; Spatial Learning ; drug effects

The present study was aimed to explore the effect of sodium nitrite on cytoskeletal protein phosphorylation and spatial learning and memory in rats. Rats were served with drinking water containing sodium nitrite (100 mg/kg) for 60 days, then, the ability of spatial learning and memory of the rats was measured by Morris water maze. Phosphorylation level of tau and neurofilament, and the expression of protein phosphatase 2A (PP2A) catalytic subunit in the hippocampus were detected by immunohistochemistry and Western blot. In comparison with the rats served with normal tap water, the rats served with sodium nitrite water showed significantly longer latency to find the hidden platform in Morris water maze (P < 0.05), elevated phosphorylation level of tau and neurofilament, and decreased expression of PP2A catalytic subunit (P < 0.05). These results indicated that administration of sodium nitrite could impair the spatial learning and memory of the rats, and the hyperphosphorylation of cytoskeletal proteins and the down-regulation of PP2A might be underlying mechanisms for the impairment.
Animals ; Cytoskeletal Proteins ; metabolism ; Down-Regulation ; Hippocampus ; metabolism ; Maze Learning ; Memory ; drug effects ; Neurofilament Proteins ; metabolism ; Phosphorylation ; Protein Phosphatase 2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium Nitrite ; pharmacology ; Spatial Learning ; drug effects ; tau Proteins ; metabolism

OBJECTIVETo evaluate the effect of Nigella sativa (NS) extract on memory performance and its possible mechanisms in scopolamine (Sco)-induced spatial memory impairment model using Morris water maze test.

METHODSThirty-two male Wistar rats were randomly divided into four groups. The control group received saline instead of both NS extract and Sco. The Sco group was treated by saline for two weeks, and was injected by Sco (2 mg/kg, intraperitoneally) 30 min before each trail in Morris water maze test. Sco+NS 200 and Sco+NS 400 groups were daily treated by 200 or 400 mg/kg of NS (intraperitoneally) for two weeks, respectively, and were finally injected by Sco 30 min before Morris water maze test. The brains of animals were removed to determine the acetylcholinesterase (AChE) activity and oxidative stress criteria in cortical tissues.

RESULTSTime latency and path length in the Sco group were significantly higher than in the control group (P<0.01), while the Sco+NS 400 group showed a significantly shorter traveled path length and time latency compared with the Sco group (P<0.01). AChE activity in the cortical tissues of the Sco group was significantly higher than the control group (P<0.01), while AChE activity in the Sco+NS 200 and Sco+NS 400 groups was lower than the Sco group (P<0.01). Following Sco administration, malondialdehyde (MDA) concentrations were increased (P<0.01) in comparison with the control group, while cortical total thiol content decreased (P<0.01). Pretreatment with extracts caused a significant elevation in cortical total thiol content (P<0.01) and reduction in cortical MDA concentration (P<0.01) compared with the Sco group.

CONCLUSIONSHydro-alcoholic extract of NS prevents Sco-induced spatial memory deficits and decreases the AChE activity as well as oxidative stress of brain tissues in rats. Our results support the traditional belief about the beneficial effects of NS in nervous system. Moreover, further investigations are needed for better understanding of this protective effect.

Acetylcholinesterase ; metabolism ; Animals ; Ethanol ; chemistry ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory Disorders ; drug therapy ; physiopathology ; Nigella sativa ; chemistry ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Reaction Time ; drug effects ; Scopolamine Hydrobromide ; Spatial Memory ; drug effects ; Sulfhydryl Compounds ; metabolism ; Water ; chemistry

BACKGROUNDThe pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San (DSS) is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus.

METHODSA total of 36 rats were randomly divided into three groups: (1) Sham group (n = 12), rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment; (2) experimental tooth movement (ETM) group (n = 12), rats received saline treatment and ETM; (3) DSS + ETM (DETM) group (n = 12), rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Morris water maze test was evaluated; immunofluorescent histochemistry was used to identify astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus.

RESULTSMaze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased compared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus (DG).

CONCLUSIONSTreatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG of hippocampus in the ETM group rats may be related with the decline of the ability of learning and memory. The ability to change the synaptic plasticity in hippocampus after DSS administration may be correlated with the alleviation of impairment of learn and memory after ETM treatment.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; drug effects ; physiology ; Male ; Memory ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; drug effects ; Tooth Movement Techniques ; adverse effects

BACKGROUNDThe mechanisms underlying diabetic encephalopathy are largely unknown, and no effective treatments are available. Catalpol has received much attention due to its numerous biological effects, especially in neuroprotective studies. The aim of this study was to investigate the effects of catalpol on cognitive functions in diabetic rats and the underlying mechanisms.

METHODSA rat model of diabetes was established by streptozotocin injection, followed by intraperitoneal infusion of catalpol after 10 weeks. Two weeks later, the Morris water maze was used to test the spatial learning performance. Nissl staining was performed to evaluate the morphological changes in the hippocampus. Expression of protein kinase Cγ (PKCγ) and caveolin-1 (Cav-1) in the hippocampus were assessed by reverse transcription PCR and Western blotting. Activities of anti-oxidative enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and levels of malonaldehyde (MDA) were measured using commercial kits.

RESULTSSignificant hippocampal neuronal injury was observed in rats with streptozotocin-induced diabetes. Moreover, cognitive dysfunction was associated with markedly increased oxidative stress in the brain. Catalpol treatment significantly attenuated cognitive deficits, neuronal damage, and oxidative stress in the brain of diabetic rats. Biochemical analyses showed that catalpol reversed the down-regulation of PKCγ and Cav-1 expression in the diabetic rats.

CONCLUSIONSSpatial memory in diabetic rats is associated with the expression of PKCγ and Cav-1. Catalpol treatment markedly attenuated oxidative stress, reversed the alteration of PKCγ, Cav-1 and spatial memory deficits.

Animals ; Caveolin 1 ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Hippocampus ; drug effects ; metabolism ; Iridoid Glucosides ; therapeutic use ; Male ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects ; Protein Kinase C ; metabolism ; Rats ; Spatial Memory ; drug effects ; physiology

Amyloid β protein (Aβ) is closely involved in the pathogenesis of Alzheimer's disease (AD), and one of the main strategies for AD treatment is antagonizing the neurotoxicity of Aβ or even clearing the Aβ deposited in the brain. The present study was aimed to observe the effects of intrahippocampal injection of Aβ₃₁₋₃₅ on the spatial learning and memory of rats by using Morris water maze technique, and explore the neuroprotective effects and possible mechanism of [Gly14]-humanin (HNG) against Aβ-induced deficits in learning behavior. The results showed that bilateral intrahippocampal injection of 2.0 nmol Aβ₃₁₋₃₅ significantly increased the mean traveled distance of rats in searching for the hidden underwater platform and decreased the distance percentage in the target quadrant in probe test after withdrawal of platform, whereas pretreatment with HNG (0.2 nmol and 2.0 nmol) suppressed Aβ₃₁₋₃₅-induced increase in the traveled distance and decrease in swimming distance percentage. Application of Genistein (40 nmol), a specific tyrosine kinase inhibitor, almost completely blocked the antagonistic effects of HNG against Aβ₃₁₋₃₅. These results indicate that HNG can dose-dependently prevent against Aβ₃₁₋₃₅-induced impairment in spatial learning and memory of rats, and the neuroprotective effects of HNG might involve the activation of endogenous tyrosine kinase pathway, suggesting that up-regulation of the tyrosine kinase signaling by using HNG might be of great significance for the improvement of cognitive function in AD.
Alzheimer Disease ; physiopathology ; Amyloid beta-Peptides ; adverse effects ; antagonists & inhibitors ; Animals ; Brain ; drug effects ; Genistein ; pharmacology ; Memory ; drug effects ; Neuroprotective Agents ; pharmacology ; Peptide Fragments ; adverse effects ; antagonists & inhibitors ; Peptides ; pharmacology ; Rats ; Spatial Learning ; drug effects