Amelioration of behavioral and histological impairments in somatosensory cortex injury rats by limbal mesenchymal stem cell transplantation.

Introduction: Cortical lesions can cause major sensory and motor impairments, representing a significant challenge in neuroscience and clinical medicine. Limbal mesenchymal stem cells (LMSCs), renowned for their remarkable ability to proliferate and distinct characteristics within the corneal epithelium, offer a promising opportunity for regenerative treatments. This study aimed to assess whether the transplantation of LMSCs could improve tactile ability in rats with lesions of the barrel cortex. Methods: In this experimental study, we divided 21 rats into three groups: a control group, a lesion group with cortical cold lesion induction but no stem cell treatment, and a group receiving LMSC transplantation following cold lesion induction. We conducted 3-week sensory assessments using a texture discrimination test and an open-field test. We also performed Nissl staining to assess changes on the cellular level. Results: Rats in the LMSC transplantation group demonstrated significant improvements in their ability to discrimination textures during the second and third weeks compared to those in the lesion group. The open-field test results showed an increased exploratory behavior of rats in the LMSC transplantation group by the third week compared to the lesion group. Additionally, Nissl staining revealed cellular alterations in the damaged cortex, with a significant distinction observed between rats in the LMSCs and lesion group. Conclusion: The findings suggest that LMSC transplantation enhances sensory recovery in rats with cortical lesions, particularly their ability to discriminate textures. LMSC transplantation benefits brain tissue reparation after a cold lesion on the somatosensory cortex.

Transmission of behavioral and cognitive impairments across generations in rats subjected to prenatal valproic acid exposure.

BACKGROUND: Autism spectrum disorder (ASD) represents an inheritable neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Numerous studies have underscored the significant roles played by genetic and environmental factors in the etiology of ASD, and these factors are known to perpetuate behavioral impairments across generations. OBJECTIVES: The primary objective of this study was to assess the behavioral and cognitive attributes in the second filial (F2) generation of male and female rats, with a particular focus on those whose parents had been exposed to valproic acid (VPA) during embryonic development. METHODS: In this study, a cohort of 32 male and 32 female rats from the second filial (F2) generation, referred to as Mother.ASD, Father.ASD, or Both.ASD, was examined. These designations indicate whether the mother, father, or both parents had experienced embryonic exposure to valproic acid (600 mg/kg, i.p.). During adolescence, the F2 pups underwent behavioral and cognitive assessments, including open field testing, marble burying, social interaction evaluations, and Morris water maze tasks. RESULTS: Our data revealed that while both the Mother.ASD and Father.ASD groups, regardless of sex, exhibited elevated anxiety-like behavior in the open field test. Only the Mother.ASD group displayed repetitive behaviors and deficits in social memory. Additionally, spatial memory impairments were observed in both sexes. These findings highlight the transmission of autistic-like behaviors in the offspring of Mother.ASD rats from both sexes. Nevertheless, future research endeavors should be more targeted in identifying the specific genes responsible for this transmission. CONCLUSION: In summary, our findings underscore the transmission of autistic-like behaviors, including anxiety-like behavior, repetitive actions, impairments in social interactions, and deficits in memory, to the offspring of the Mother.ASD group, irrespective of their sex.

Effects of music on cognitive behavioral impairments in both sex of adult rats exposed prenatally to valproic acid.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive behaviors and interests. In previous studies, music has been identified as an intervention therapy for children with ASD. OBJECTIVES: The present study evaluated the effects of music on cognitive behavioral impairments in both sexes of adult rats exposed prenatally to Valproic acid. METHODS: For induction of autism, pregnant female rats were pretreated with either saline or VPA (600 mg/kg.i.p.) at gestational day (GD) 12.5. Male and female offspring were divided into Saline.Non-Music, VPA.Non-Music, Saline.Music, and VPA.Music groups. The adult rats in the music groups were exposed to Mozart's piano sonata K.448 for 30 days (4 h/day), from postnatal day (PND) 60 to 90. Social interaction and Morris water maze (MWM) tasks were tested at PND 90. RESULTS: Our results revealed that prenatal exposure to VPA decreased sociability and social memory performance in both sexes of adult rats. Moreover, prenatal exposure to VPA created learning and memory impairments in both sexes of adult rats in the MWM task. Music intervention improved sociability in both sexes of VPA-exposed rats and social memory in both sexes of VPA-exposed rats, especially in females. Furthermore, our results revealed that music ameliorated learning impairments in VPA-exposed female rats in the MWM task. In addition, music improved spatial memory impairments in VPA-exposed rats of both sexes, especially in females, which needs more investigation in molecular and histological fields in future studies. CONCLUSION: Music intervention improved sociability and social memory in adult VPA-exposed rats, especially in female animals. Furthermore, music improved memory impairments in VPA-exposed rats of both sexes. It seems that music had a better influence on female rats. However, future studies need more investigations in molecular and histological fields.

Aggravation of cognitive impairments in the valproic acid-induced animal model of autism in BALB/c mice infected with Toxoplasma gondii.

PURPOSE: Toxoplasmosis is a disease caused by infection with a type of coccidial protozoan parasite called Toxoplasma gondii. The relationship between toxoplasmosis and cognitive disorders in neurodegenerative diseases has been proven. There is also evidence that children born to Toxoplasma-infected mothers are more likely to develop autism. METHODS: In the present study, Toxoplasma-infected pregnant BALB/c mice were given valproic acid to induce autism in their male offspring, and their social behaviors, learning, and memory were examined. Chronic toxoplasmosis was established in BALB/c mice by intraperitoneal injection of cyst form of T. gondii. To induce autism, 600 mg/kg of valproic acid was injected intraperitoneally into mice on the 12.5th day of pregnancy. The behavioral experiments, such as social interaction, novel object recognition, and passive avoidance tasks, were performed on male offspring at 50 days. RESULTS: Toxoplasma and valproic acid during the embryonic period caused social communication deficits and disrupted recognition memory and avoidance memory in offspring. Our findings showed that administering valproic acid to Toxoplasma-infected mothers exacerbates cognitive disorders in their offspring.

Impact of Sleep Deprivation on the Brain's Inflammatory Response Triggered by Lipopolysaccharide and Its Consequences on Spatial Learning and Memory and Long-Term Potentiation in Male Rats.

INTRODUCTION: Both sleep deprivation (SD) and inflammation can negatively affect cognitive function. This study aimed to investigate how SD impacts the brain's inflammatory response to lipopolysaccharide (LPS) and its subsequent effects on cognitive functions. METHODS: To this end, male rats were tested through a Morris water maze (MWM) to assess their spatial learning and memory. Also, in vivo field potential recordings (to evaluate synaptic plasticity) were done in the Saline, SD, LPS1 (1 mg/kg/7 days), and LPS1+SD groups. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Based on the results, the LPS1+SD group showed increased total distance and escape latency compared to the other groups in the MWM test. Besides, the LPS1+SD group exhibited a significant decrease in long-term potentiation (LTP) induction and maintenance in the CA1 area of the brain. Finally, the inflammatory cytokine interleukin-1ß (IL-1ß) levels were significantly higher in the LPS1+SD group than in the Saline group. CONCLUSION: These findings suggest that the combined effects of SD and brain inflammatory response can have more harmful effects on cognitive function, LTP, and inflammatory factors than either SD or LPS1 alone.

Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist.

Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behavior. Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R). In this study, the effects of ciproxifan (CPX) (1 and 3 mg/kg, intraperitoneally) on cognitive impairments in rat pups exposed to valproic acid (VPA) (600 mg/kg, intraperitoneally) wereexamined on postnatal day 48-50 (PND 48-50) using marble-burying task (MBT), open field, novel object recognition (NOR), and Passive avoidance tasks. Famotidine (FAM) (10, 20, and 40 mg/kg, intraperitoneally) was also used to determine whether histaminergic neurotransmission exerts its procognitive effects via H2 receptors (H2Rs). Furthermore, a histological investigation was conducted to assess the degree of degeneration of hippocampal neurons. The results revealed that repetitive behaviors increased in VPA-exposed rat offspring in the MBT. In addition, VPA-exposed rat offspring exhibited more anxiety-like behaviors in the open field than saline-treated rats. It was found that VPA-exposed rat offspring showed memory deficits in NOR and Passive avoidance tasks. Our results indicated that 3 mg/kg CPX improved cognitive impairments induced by VPA, while 20 mg/kg FAM attenuated them. We concluded that 3 mg/kg CPX improved VPA-induced cognitive impairments through H3Rs. The histological assessment showed that the number of CA1 neurons decreased in the VPA-exposed rat offspring compared to the saline-exposed rat offspring, but this decrease was not significant. The histological assessment also revealed no significant differences in CA1 neurons in VPA-exposed rat offspring compared to saline-exposed rat offspring. However, CPX3 increased the number of CA1 neurons in the VPA + CPX3 group compared to the VPA + Saline group, but this increase was not significant. This study showed that rats prenatally exposed to VPA exhibit cognitive impairments in the MBT, open field, NOR, and Passive avoidance tests, which are ameliorated by CPX treatment on PND 48-50. In addition, morphological investigations showed that VPA treatment did not lead to neuronal degeneration in the CA1 subfield of the hippocampus in rat pups.

Music alleviates cognitive impairments in an animal model of autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms including impairment in social communication and restrictive and repetitive behaviors and interests. Music has emerged in the past decade as an intervention therapy for children with ASD. The aim of the present study was to evaluate the effects of music on cognition impairments in the valproic acid (VPA) rat model of autism. The VPA was administered for animal modeling of autism on embryonic day 12.5 (E12.5) (600 mg/kg). Male and female pups were sub divided into four main groups (Saline.Non-music, VPA.Non-music, Saline.Music, and VPA.Music). The rats in the music groups were exposed to Mozart's piano sonata K.448 for 30 days (4 h/day), from postnatal day (PND) 21 to 50. Autistic-like behaviors were tested using a social interaction, the Morris water maze (MWM), and a passive avoidance tasks at the end of the PND 50. Our results demonstrated that VPA-exposed rat pups had significantly lower sociability and social memory performance compared with the saline-exposed rats in both sexes. VPA-exposed rat pups exhibited learning and memory impairments in the MWM and passive avoidance tasks. Our results demonstrated that music improved sociability in VPA-exposed rats, especially in males. Furthermore, our findings revealed that music improved learning impairments in VPA-exposed male rats in MWM task. In addition, music improved spatial memory impairments in VPA-exposed rats of both sexes. We also found that music improved passive avoidance memory impairments in VPA-exposed rats of both sexes, especially in females. More investigation in future studies are needed.

Histamine H3 receptor antagonist, ciproxifan, alleviates cognition and synaptic plasticity alterations in a valproic acid-induced animal model of autism.

RATIONALE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and cognitive behaviors. Histamine H3 receptor (H3R) antagonists are considered as therapeutic factors for treating cognitive impairments. OBJECTIVES: The aim of the present study was to evaluate the effects of the H3R antagonist, ciproxifan (CPX), on cognition impairment especially, spatial learning memory, and synaptic plasticity in the CA1 region of the hippocampus in autistic rats. METHODS: Pregnant rats were injected with either valproic acid (VPA) (600 mg/kg, i.p.) or saline on an embryonic day 12.5 (E12.5). The effects of the H3R antagonist, ciproxifan (CPX) (1, 3 mg/kg, i.p.), were investigated on learning and memory in VPA-exposed rat pups and saline-exposed rat pups using Morris water maze (MWM) and social interaction tasks. The H2R antagonist, famotidine (FAM) (10, 20, 40 mg/kg, i.p.), was used to determine whether brain histaminergic neurotransmission exerted its procognitive effects through the H2R. In addition, synaptic reinforcement was evaluated by in vivo field potential recording. RESULTS: The results showed that VPA-exposed rat pups had significantly lower sociability and social memory performance compared to the saline rats. VPA-exposed rat pups exhibited learning and memory impairments in the MWM task. In addition, VPA caused suppression of long-term potentiation (LTP) in the CA1 area of the hippocampus. Our results demonstrated that CPX 3 mg/kg improved VPA-induced cognitive impairments and FAM 20 mg/kg attenuated cognitive behaviors as well as electrophysiological properties. CONCLUSIONS: CPX 3 mg/kg improved VPA-induced impairments of LTP as well as learning and memory deficits through H2R.

Nitric oxide role in anxiety-like behavior, memory and cognitive impairments in animal model of chronic migraine.

The occurrence of cognitive dysfunctions and anxiety and mood disorders has been shown to be higher in migraine patients. Nitric Oxide (NO) is a significant neurotransmitter in the pathophysiology of migraine, anxiety and neurodegenerative disorders. Therefore, the present study was conducted to evaluate the role of NO system in migraine-induced memory impairment and anxiety like behaviors. Nitroglycerin (NTG) was administered to the animals as an animal model of migraine and pretreatment with L-Arginine, L-NAME and saline were implemented to evaluate the role of NO system in possible cognitive impairments in animal model of migraine. Avoidance learning and memory performance, object recognition memory, anxiety-like behavior and motor activity were assessed using a shuttle box apparatus, novel object recognition, elevated plus-maze, and open field tests respectively. The data showed that the injection of nitroglycerin disturbs learning and memory and elicit anxiety like behavior in the animals. L-NAME administration suppressed the observed effect of nitroglycerin on memory and anxiety. Overall, the results indicated that nitric oxide system is implicated in memory impairments and anxiety like behavior in an animal model of migraine.

Intergenerational effects of maternal separation on cognitive abilities of adolescent rats.

Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother-infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA-induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F2 ) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (postnatal day (PND) 1-21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F2 pups were tested during adolescence. Our results showed that although the mother-MS group of both sexes showed normal cognitive behavior, father-MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father-MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS-induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one's parents could be inherited in the following generation in a sex-dependent manner.

Amelioration of Prenatal Lead-Induced Learning and Memory Impairments by Methanolic Extract of Zataria Multiflora in Male Rats.

INTRODUCTION: The current study aimed at evaluating the effects of Zataria Multiflora (ZM) on learning and memory of adult male offspring rats with prenatal lead-exposure. METHODS: Pregnant rats in the case group received tap water containing 0.2% lead acetate throughout the gestation period. Control rats had free access to lead-free tap water. Two male offspring (two-month-old, weighing 180-200 g) from each mother were randomly selected and treated with either Z. Multiflora (50, 200, 400, and 800 mg/kg/Intraperitoneally (I.P)/20 day) or saline. Spatial memory of the control, saline, and ZM-treated rats was evaluated by a training trial and probe test using Morris water maze (6-8 rat/group). RESULTS: The obtained results showed memory deficits including increased escape latency, and a greater traveled distance, as well as decrements in the frequency of crossings into target quadrants in prenatally lead-exposed male offspring compared with the controls. ZM treatment (200 mg/kg/i.p) ameliorated the memory deficits in male offspring by increasing the time spent and traveled distance in the trigger zone (P<0.01 vs. saline).There was no significant difference in swimming speed between the groups. CONCLUSION: The results showed memory deficits in prenatally lead-exposed male offspring. ZM treatment (especially 200 mg/kg) had beneficial effects on cognitive behavior and was indicated as the improvement of lead-induced memory deficits in prenatally lead-exposed male rats. The exact mechanism(s) is not determined yet, but it could be mediated through the anticholinesterase and antioxidant effects and also alterations in Central Nervous System (CNS) and neurotransmission in the central nervous system.