Passive Avoidance Memory Research Articles

Role of BIX01294 in the intracranial inhibition of H3K9 methylation lessens neuronal loss in vascular dementia model.

Dementia develops as a result of multiple factors, including cerebrovascular disease which is called vascular dementia (VD). Histone-3 lysine-9 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expressions. So, we aimed to determine how H3K9me2 inhibitor (BIX01294) affects neuronal damage in VD. An in vivo model of VD was used followed by BIX01294 treatment. Behavioral tests, hematoxylin, and eosin (H&E), Congo red, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were carried out. Hippocampal phosphorylated cyclic-AMP responsive element binding protein (p-CREB), c-fos, brain-derived neurotrophic factor (BDNF), and H3K9me2, were detected by western blot analysis technique. Neurological deficit and anxiety-related behavior significantly reduced in the treatment group compared to the VD group (p < 0.05). BIX01294 improved spatial and passive avoidance memory (p < 0.01 and p < 0.05, respectively) compared to the VD group. Treatment with BIX01294 restored the level of p-CREB/CREB ratio (p < 0.05), cfos (p < 0.01), BDNF (p < 0.01), and suppressed H3K9me2 (p < 0.001) when compared to the VD group. BIX01294 microinjection reduced the apoptosis level in TUNEL staining (p < 0.05), and raised neural cell count in H&E staining (p < 0.01); amyloid beta accumulation significantly decreased in the treatment group (p < 0.05) compared to the VD group. In conclusion, long-term treatment with a low dose of BIX01294 can prevent the progression of neuronal loss in VD model by raising the expression of neurotrophic factors, and reducing the apoptosis level.

Can L-Methionine and S-Adenosyl-L-Methionine effectively mitigate scopolamine-induced cognitive and motor deficits in mice?

Motor balance deficits often coincide with cognitive deficits in older adults. Current medications provide temporary relief with several potential side effects. Essential amino acids and their derivatives, such as S-Adenosyl-L-Methionine (SAMe), can improve nerve function, mood regulation, and neuroprotection against neurodegenerative diseases. This study investigated the protective effects of SAMe in scopolamine-degraded memory, and motor balance in an animal model. To evaluate the possible effects of SAMe on cognitive and motor balance improvement, both Shuttle box and rotarod methods were performed in seven groups of animals (n=7). The mice groups received the saline (control), scopolamine, scopolamine+rivastigmine, scopolamine +methionine, and scopolamine+ three different doses of SAMe daily and separately for two weeks. Data were analyzed independently by one-way ANOVA and P<0.05 was considered significant. SAMe 150 mg/kg worsened scopolamine-induced memory impairment (P<0.001), while methionine (100 mg/kg) or SAMe (only 100 mg/kg) together with scopolamine could reduce the duration of the animal's presence in the dark chamber (P<0.05). Daily administration of methionine and SAMe at the rate of 100 mg/kg daily could significantly improve the decrease in motor balance caused by scopolamine (P<0.05). Rivastigmine improved memory and motor balance impairment caused by scopolamine (P<0.05). No difference between SAMe and L-methionine for memory, and balance. The results suggest that while L-methionine and SAMe may not be effective in improving memory impairments (Even SAMe high doses can aggravate the destruction of passive avoidance memory), they may be beneficial in enhancing motor balance.

Ascending Vagal Sensory and Central Noradrenergic Pathways Modulate Retrieval of Passive Avoidance Memory in Male Rats.

Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay "gut feelings" to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. These new findings support the view that gut vagal afferents and the cNTSNA-to-vlBNST circuit play a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.

Ameliorative effects of Akkermansia muciniphila on anxiety-like behavior and cognitive deficits in a rat model of Alzheimer’s disease

Alzheimer’s Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic–pituitary–adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores Akkermansia muciniphila’s impact on preventing AD. This research investigates the effect of A. muciniphila consumption (1 × 109 CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with A. muciniphila). A. muciniphila gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of A. muciniphila treatment, anxiety-like behavior significantly decreased. The AD group receiving A. muciniphila showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ) decreased. A. muciniphila effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis.

Deregulation of Melatonin Receptors and Differential Modulation of After-Hyperpolarization and Ih Currents Using Melatonin Treatment Due to Amyloid-β-Induced Neurotoxicity in the Hippocampus.

Treatment with melatonin is routinely prescribed for its potent antioxidant and cognitive-promoting effects, nevertheless, it has yet to find neuromodulatory effects in normal and disease conditions. Therefore, to investigate its neuromodulatory mechanisms, melatonin was systemically administered over 10 consecutive days to both intracortical normal saline- and amyloid-β 1-42 (Aβ) peptide-injected rats. At the behavioral level, treatment with melatonin was associated with reduced efficacy in restoring Aβ-induced deficit in passive-avoidance memory. Whole-cell patch-clamp recordings from CA1 pyramidal neurons revealed that melatonin treatment reduced spontaneous and evoked intrinsic excitability in control rats while exerting a reduction of spontaneous, but not evoked activity, in the Aβ-injected group. Interestingly, treatment with melatonin enhances after-hyperpolarization in control, but not Aβ-injected rats. In contrast, our voltage-clamp study showed that Ih current is significantly enhanced by Aβ injection, and this effect is further strengthened by treatment with melatonin in Aβ-injected rats. Finally, we discovered that the transcription of melatonin receptors 1 (MT1) and 2 (MT2) is significantly upregulated in the hippocampi of Aβ-injected rats. Collectively, our study demonstrates that systemic treatment with melatonin has differential neuromodulation on CA1 neuronal excitability, at least in part, via differential effects on after-hyperpolarization and Ih currents due to Aβ-induced neurotoxicity.

The Biochemical Effects of Hydroalcoholic Extract of Quercus brantii Fruit on Morphine-Induced Amnesia in the Presence and Absence of Cholinergic Muscarinic Receptors in Adult Male Mice

Background: In our previous study, we demonstrated that oak hydroalcoholic extract improves memory impairment in a postpartum depression model due to its antioxidant properties. The purpose of this study is to further investigate the effect of oak on another amnesia model and explore the mediating role of cholinergic muscarinic receptors. Objectives: This study investigated the effect of hydroalcoholic extract of oak fruit on amnesia induced by morphine in the presence and absence of cholinergic muscarinic receptors, as well as changes in serum biochemical factors. Methods: In this experimental study, adult male mice were divided into groups: Control and morphine-receiving (5 and 7.5 mg/kg) groups to induce amnesia after training. In the groups receiving 7.5 mg/kg morphine, oak extract (1 and 10 mg/kg) was administered one day after training and continued for one week. Atropine (0.1 and 1 mg/kg) was injected only on the first day after training and before the oak extract injection. Passive avoidance memory was evaluated 1, 3, and 7 days after training using a step-down device. Motor activity was assessed using the open field test. Blood biochemical factors, including triglycerides, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total antioxidant capacity (TAC), were measured after one week of injections. Results: Morphine (7.5 mg/kg) impaired memory on days 1 and 7 (P &lt; 0.05), while oak extract (1 and 10 mg/kg) improved memory (P &lt; 0.001). Additionally, the oak extract maintained its enhancing effect even in the presence of atropine, a cholinergic muscarinic system antagonist. Oak extract significantly increased HDL and TAC levels but did not affect LDL, cholesterol, and triglyceride levels. Conclusions: These findings suggest that oak extract can improve morphine-induced amnesia due to its antioxidant effect, without involving the cholinergic system. Additionally, oak extract can increase beneficial lipids without affecting harmful lipids.

Exploring the impact of acetylsalicylic acid and conditioned medium obtained from mesenchymal cells, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with hippocampal injury.

The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.

Protective effects of L-carnitine against beta-amyloid-induced memory impairment and anxiety-like behavior in a rat model of Alzheimer's disease

Alzheimer's disease (AD), the most common cause of dementia, leads to neurodegeneration and cognitive decline. We investigated the therapeutic effects of L-carnitine on cognitive performance and anxiety-like behavior in a rat model of AD induced by unilateral intracerebroventricular injection of β-amyloid1-42 (Aβ1-42). L-carnitine (100 mg/kg/day) was administered intraperitoneally for 28 consecutive days. Following this, the open-field test, novel object recognition test, elevated plus-maze test, Barnes maze test, and passive avoidance learning test were used to assess locomotor activity, recognition memory, anxiety-like behavior, spatial memory, and passive avoidance memory, respectively. Plasma and hippocampal oxidative stress markers, including total oxidant status (TOS) and total antioxidant capacity (TAC), were examined. In addition, histological investigations were performed in the dentate gyrus of the hippocampus using Congo red staining and hematoxylin and eosin staining. The injection of Aβ1-42 resulted in cognitive deficits and increased anxiety-like behavior. These changes were associated with an imbalance of oxidants and antioxidants in plasma and the hippocampus. Also, neuronal death and Aβ plaque accumulation were increased in the hippocampal dentate gyrus region. However, injection of L-carnitine improved recognition memory, spatial memory, and passive avoidance memory in AD rats. These findings provide evidence that L-carnitine may alleviate anxiety-like behavior and cognitive deficits induced by Aβ1-42 through modulating oxidative-antioxidant status and preventing Aβ plaque accumulation and neuronal death.

Early-life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions.

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiologicaland cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early-life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para-chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10-20, followed by sleep deprivation-induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain-derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions.

Protective effects of selegiline against amyloid beta-induced anxiety-like behavior and memory impairment.

Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1-42 (Aβ1-42). Oral administration of SEL at a dose of 0.5mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats. These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aβ through modulation of oxidative-antioxidant status.

Evaluation of ivermectin and vitamin E based combination with antiseizure rufinamide drug for mitigation of pentylenetetrazole-induced kindling, behavioral challenges and histopathological aberrations.

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.

Protective effects of rosmarinic acid against autistic-like behaviors in a mouse model of maternal separation stress: behavioral and molecular amendments.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with worldwide increasing incidence. Maternal separation (MS) stress at the beginning of life with its own neuroendocrine changes can provide the basis for development of ASD. Rosmarinic acid (RA) is a phenolic compound with a protective effect in neurodegenerative diseases. The aim of this study was to determine the effect of RA on autistic-like behaviors in maternally separated mice focusing on its possible effects on neuroimmune response and nitrite levels in the hippocampus. In this study, 40 mice were randomly divided into five groups of control (received normal saline (1 ml/kg)) and MS that were treated with normal saline (1 ml/kg) or doses of 1, 2, and 4 mg/kg RA, respectively, for 14 days. Three-chamber sociability, shuttle box, and marble burying tests were used to investigate autistic-like behaviors. Nitrite level and gene expression of inflammatory cytokines including TNF-α, IL-1β, TLR4, and iNOS were assessed in the hippocampus. The results showed that RA significantly increased the social preference and social novelty indexes, as well as attenuated impaired passive avoidance memory and the occurrence of repetitive and obsessive behaviors in the MS mice. RA reduced the nitrite level and gene expression of inflammatory cytokines in the hippocampus. RA, probably via attenuation of the nitrite level as well as of the neuroimmune response in the hippocampus, mitigated autistic-like behaviors in maternally separated mice.

Cacao consumption improves passive avoidance memory impairment in a rat model of Alzheimer's disease: the role of hippocampal synaptic plasticity and oxidative stress.

Introduction: Alzheimer's disease (AD) causes progressive loss of cognitive function and synaptic plasticity, which is the most common form of dementia. The present study was designed to scrutinize the effects of cacao on passive avoidance memory function and to identify the roles of hippocampal synaptic plasticity and oxidative stress in an AD rat model induced by unilateral intracerebroventricular (UICV) injection of amyloid-beta (Aβ). Methods: Oral administration of cacao (500 mg/kg/ day) was given for 2 consecutive months. A memory retention test was conducted 24 h after passive avoidance training was completed. Subsequently, the amplitude of population spike (PS) and slope of field excitatory postsynaptic potentials (fEPSPs) were assessed at hippocampal long-term potentiation (LTP) in perforant pathway-dentate gyrus (PP-DG) synapses. Moreover, total thiol group (TTG) and malondialdehyde (MDA) concentrations were evaluated in the plasma. Furthermore, compact Aβ plaques were detected in the hippocampal DG by performing Congo red staining. Results: As a result of AD induction, passive avoidance memory was impaired; also, reduced fEPSP slopes, PS amplitudes, and content of TTG, and increase in MDA levels in the rats were observed. In contrast, cacao treatment ameliorated passive avoidance memory impairment, improved hippocampal LTP impairment, modulated oxidative-antioxidative status, and delayed Aβ plaques production in AD rats. Disscussion: Conclusively, cacao alleviates Aβ-induced cognitive deficit, probably by the amelioration of hippocampal LTP impairment, modulation of oxidative-antioxidative status, and inhibition of Aβ plaque accumulation.

Coenzyme Q10 and exercise training reinstate middle cerebral artery occlusion-induced behavioral deficits and hippocampal long-term potentiation suppression in aging rats.

Patients experience post-stroke cognitive impairment during aging. To date, no specific treatment solution has been reported for this disorder. The purpose of this study was to evaluate the effects of exercise training and coenzyme Q10 supplementation on middle cerebral artery occlusion (MCAO) induced behavioral impairment, long-term potentiation inhibition and cerebral infarction size in aging rats. Fifty aging male rats underwent MCAO surgery and were randomly distributed in to the following groups: 1-Sham, 2- control, 3- Coenzyme Q10, 4- Exercise training and 5- Exercise training with Q10 supplementation (Ex + Q10). Aerobic training groups were allowed to run on a treadmill for 12 weeks. Q10 (50mg/kg) was administered intragastrically by gavage. Morris water maze, shuttle box and elevated plus maze tests were used to evaluate cognitive function. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) in the dentate gyrus area were recorded as a result of perforant pathway electrical stimulation. Our study showed that Q10 and aerobic training alone ameliorate spatial memory in the acquisition phase, but have no effect on spatial memory in the retention phase. Q10 and exercise training synergistically promoted spatial memory in the retention phase. Q10 and exercise training separately and simultaneously mitigated cerebral ischemia-induced passive avoidance memory impairment in acquisition and retention phases. The EPSP did not differ between the groups, but exercise training and Q10 ameliorate the PS amplitude in hippocampal responses to perforant path stimulation. Exercising and Q10 simultaneously reduced the cerebral infarction volume. Collectively, the findings of the present study imply that 12 weeks of aerobic training and Q10 supplementation alone can simultaneously reverse cerebral ischemia induced neurobehavioral deficits via amelioration of synaptic plasticity and a reduction in cerebral infarction volume in senescent rats.

The association of caffeine and nandrolone decanoate modulates aversive memory and nociception in rats

Caffeine and anabolic–androgenic steroids (AAS) are commonly used to improve muscle mass and athletic performance. Nandrolone Decanoate (ND) is one of the most abused AAS worldwide, leading to behavioral changes in both humans and rodents. Caffeine, the most widely consumed psychostimulant globally, is present in various thermogenic and gym supplements. Low and moderate doses of caffeine antagonize adenosine receptors and have been linked to improved memory and pain relief. We have previously demonstrated that consuming caffeine prevents the risk-taking behavior triggered by nandrolone. In this study, we aimed to investigate the long-term effects of ND and caffeine, either alone or in combination, on passive avoidance memory and nociception. We used the step-down and hot-plate tasks in male and female Lister Hooded rats. Our results confirmed the antinociceptive effect of caffeine and indicated that chronic administration of the ND-caffeine association promotes the evocation of aversive memory in female rats.

Effects of chronic social equality and inequality conditions on passive avoidance memory and PTSD-like behaviors in rats under chronic empathic stress

Introduction: Social inequality conditions induce aversion and affect brain functions and mood. This study investigated the effects of chronic social equality and inequality (CSE and CSI, respectively) conditions on passive avoidance memory and post-traumatic stress disorder (PTSD)-like behaviors in rats under chronic empathic stress. Methods: Rats were divided into different groups, including control, sham-observer, sham-demonstrator, observer, demonstrator, and co-demonstrator groups. Chronic stress (2 hours/day) was administered to all stressed groups for 21 days. Fear learning, fear memory, memory consolidation, locomotor activity, and PTSD-like behaviors were evaluated using the passive avoidance test. Apart from the hippocampal weight, the correlations of memory and right hippocampal weight with serum corticosterone (CORT) levels were separately assessed for all experimental groups. Results: Latency was significantly higher in the demonstrator and sham-demonstrator groups compared to the control group. It was decreased significantly in other groups compared to the control group. Latency was also decreased in the observer and co-demonstrator groups compared to the demonstrator group. Moreover, the right hippocampal weight was significantly decreased in the demonstrator and sham-demonstrator groups compared to the control group. Pearson’s correlation of memory and hippocampal weight with serum CORT levels supported the present findings. Conclusion: Maladaptive fear responses occurred in demonstrators and sham-demonstrators. Also, extremely high levels of psychological stress, especially under CSI conditions (causing abnormal fear learning) led to heightened fear memory and PTSD-like behaviors. Right hippocampal atrophy confirmed the potential role of CSI conditions in promoting PTSD-like behaviors. Compared to inequality conditions, the abnormal fear memory was reduced under equality conditions.

Gut-brain barrier dysfunction bridge autistic-like behavior in mouse model of maternal separation stress: A behavioral, histopathological, and molecular study.

Autism spectrum disorder (ASD) is a fast-growing neurodevelopmental disorder throughout the world. Experiencing early life stresses (ELS) like maternal separation (MS) is associated with autistic-like behaviors. It has been proposed that disturbance in the gut-brain axis-mediated psychiatric disorders following MS. The role of disruption in the integrity of gut-brain barrier in ASD remains unclear. Addressing this knowledge gap, in this study we aimed to investigate role of the gut-brain barrier integrity in mediating autistic-like behaviors in mouse models of MS stress. To do this, mice neonates are separated daily from their mothers from postnatal day (PND) 2 to PND 14 for 3hours. During PND58-60, behavioral tests related to autistic-like behaviors including three-chamber sociability, shuttle box, and resident-intruder tests were performed. Then, prefrontal cortex (PFC), hippocampus, and colon samples were dissected out for histopathological and molecular evaluations. Results showed that MS is associated with impaired sociability and social preference indexes, aggressive behaviors, and impaired passive avoidance memory. The gene expression of CLDN1 decreased in the colon, and the gene expression of CLDN5, CLDN12, and MMP9 increased in the PFC of the MS mice. MS is associated with decrease in the diameter of CA1 and CA3 areas of the hippocampus. In addition, MS led to histopathological changes in the colon. We concluded that, probably, disturbance in the gut-brain barrier integrities mediated the autistic-like behavior in MS stress in mice.

Interaction effect of crocin and citalopram on memory and locomotor activity in rats: an insight into BDNF and synaptophysin levels in the hippocampus.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive-compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50mg/kg, and crocin was injected at the dose of 50mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin.

Effects of Aerobic Interval Training Along with Ginkgo biloba Supplementation on Passive Avoidance Memory and GDNF Gene Expression in Alzheimer Rats

Effects of Aerobic Interval Training Along with Ginkgo biloba Supplementation on Passive Avoidance Memory and GDNF Gene Expression in Alzheimer Rats

Chronic REM sleep deprivation leads to manic- and OCD-related behaviors, and decreases hippocampal BDNF expression in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats. The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg. REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior. Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated.