Effects of Zinc/Iron oxide nanocomposites on learning and spatial memory in rats exposed to noise stress
Fahimeh Ardeshiri-Lordejani1, Tayebe Sharifi1,*, Mahmoud Salami1,2, Ahmad Qazanfari1, Masoud Soheili1,2
1 Department of Psychology, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
2 Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I. R. Iran
*Corresponding author. Tel: +98 9131853184; E-mail address: sharifi_ta@yahoo.com (T. Sharifi)
Abstract
To some degree, Environmental stressors such as road traffic noise affect all organisms as well as their populations, communities, and ecoscapes. Evidence indicates that noise exposure can lead to changes in learning and spatial memory. Notably, in recent years nanotechnologies have been applied to human health with promising results. The purpose of this study was to examine the effects of Zinc/Iron oxide nanocomposites on spatial learning and memory in rats exposed to noise stress. Using gelatin, Zinc/Iron oxide nanocomposites were synthesized by the green method. Four groups of rats were exposed to sound stress for 12 days. Three groups received 1.25, 2.5, and 5 mg/kg of Zinc/Iron oxide nanocomposites (ST+N) before the noise stress. Also, three control animals received the same doses of the nanocomposites (CO+N). One group of the stressed (ST) and control (CO) rats received saline. The animals were introduced to the Morris water maze (MWM) for the assessment of learning and spatial memory. We observed a significant difference between the spatial memory of the CO and ST animals. but no significant differences were found between the spatial learning of the CO and ST rats or between the CO+N and ST+N groups.
Keywords: Zinc/Iron oxide nanocomposites, learning and spatial memory, noise stress, Morris water maze (MWM)
Introduction
Noise pollution or unwanted sound is considered one of the products of the modern lifestyle that causes great damage to various systems of the body including the nervous system and is a threat to health and well-being(1) This is considered as a critical concerning issue of the industrialized societies. All vital physiologic systems of the body are inherently programmed, through rigorous fine-tuning achieved during evolution, to preserve a predefined steady state (homeostasis or eustasis), which is essential for life and well-being (2). This optimal equilibrium is constantly challenged by adverse forces which are stressors (3, 4). Thus, stress is as a state of disharmony or cacostasis that is counteracted by an intricate repertoire of physiologic and behavioral responses which aim to maintain or reestablish the threatened homeostasis. The adaptive stress response is mediated by a complex and interconnected neuroendocrine, cellular, and molecular infrastructure which constituents the stress system and is located in both the central nervous system (CNS) and the periphery (5, 6). The adaptive response of each individual to stress is determined by a multiplicity of genetic, environmental, and developmental factors. Changes in the ability to effectively respond to stressors may lead to disease. Under normal conditions stress changes are adaptive and improve the chances of survival. However, as the potency of the stressors increases the specificity of the adaptive response decreases (7). Due to their high interfacial reactivity and remarkable physiochemical properties, nanoparticles have been widely used in the recent years in multiple applications. Both natural and synthetic nanoparticles have been utilized in environmental problems, or at the interface of chemistry, engineering, physics, biology, and medicine. Extensive use of nanoparticles in various fields causes environmental pollution (8). Due to their high permeability, nanoparticles easily cross the blood-brain barrier (BBB) and they can enter the human body in large quantities (9).Therefore, these substances may cause negative effects on humans and other organisms than ordinary substances may do (10).
Destructive or beneficial effects of nanoparticles on cognitive function and psychological behavior have recently been the target of extensive studies (11).Animal and human bodies respond to stress in two ways: a) rapid response, during which the autonomic nervous system (ANS) is activated leading to the secretion of the catecholamines epinephrine and norepinephrine in the adrenal gland, that results in typical symptoms of stress, and b) slow response, during which the hypothalamic- pituitary-adrenal (HPA) axis is activated, leading to increased secretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) (12). ACTH stimulates the adrenal cortex, giving rise to the secretion of glucocorticoids (GCs). The most important of GCs are
cortisol in humans and corticosterone in rats (CORT) (13). It is shown that exposing pregnant rats to noise stress for two to four hours/day increase serum corticosterone level (14). Also, the serum level of corticosterone increases significantly in offspring exposed to maternal separation stress (15). Oxidative stress, which is caused by an imbalance between the formation of free oxygen radicals and the inactivation of these species by the antioxidant defense system, can cause oxidative damage to various intracellular and extracellular molecules (16). These detrimental effects generally appear after exposure to a relatively large amount of reactive oxygen species (ROS). Oxygen radicals are generated in the body as byproducts of oxidative metabolism (12). To protect the oxidative cycle and stability, cells have developed defense mechanisms that strike the right balance between antioxidant and oxidant molecules (17). Zinc ions participate in the mechanisms of the enzyme superoxide dismutase, thus playing an important role in oxidative balance and anxiety control (18).A host of environmental changes, hormones and stressors have similar effects on learning and memory (19). Spatial learning is the processing of information about a person's position in the surrounding space, the spatial position of a person's limbs relative to each other or to a spatial position, or finding an object or other being in space(19).But spatial memory is the consolidation of information related to spatial learning (19).Memory is a mechanism for encrypting, storing, and retrieving stored information (20). Given that learning and memory are two interrelated processes that occur along the same lines. In fact, memory is the consolidation of information received from the environment during the learning phase in the brain (19).
Materials and Methods Materials
The produced materials of Sigma-Aldrich, such as Iron (III) Nitrate Nonahydrate Fe(NO3)3.9H2O and Zinc nitrate (Zn(NO3)2 and materials of Merc Co, include methanol and chloroform, were applied in this study. Also, colorless, odorless, and essential oil-free animal (edible) gelatins were prepared from the traditional medicine market.
Synthesis of zinc/ iron oxide nanocomposites (ZIONC)
In the present study, a modified sol-gel method was employed for the synthesis of ZIONC.
Next, (Zn(NO3)2 and iron nitrate were dissolved in 50 mL of deionized water in a 1:2 stoichiometric ratio and stirred magnetically for preparing a homogeneous solution. In the next
step, 2g of natural animal gelatin was added to deionized water, stirred, and heated at 80°C to provide a viscous and uniform gel. The prepared metal salt solution was then added to the gel and stirred (by a mechanical stirrer) until the zinc and iron ions were uniformly distributed throughout the mentioned gel. Here, the container containing the sample was first placed at 90 °C for 24 hours for dehumidifying until a uniform, low-moisture, and faded brick red color gel was produced due to the formation of a set complex of iron ions and acetylacetonate. Then, the processed gel was placed in a muffle furnace at 550 °C for 4 hours. Since most of the gel is released as smoke, vapor, and foul-smelling gases up to about 300 °C, it is recommended that the previous step be performed under a fume hood and/ or laboratory ventilation. The obtained product was further treated (washed) with distilled water and ethanol. Next, an Ultrasonic Bath and a deionized water solvent were employed to disperse the nanoparticles and separate possible organic matter. Finally, ZIONC was dried in an oven at 75 °C for 24 hours after filtering the resulting mixture (21).
Characterization
At this stage, different techniques, such as Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), photoluminescence spectroscopy (PL), and transmission electron microscope (TEM), were employed toward characterizing synthesized ZIONC powder. Also, the size of the synthesized crystallite was estimated using the Debye‐Scherrer equation through the following formula:
Equation (1)
𝐷 =
κλβcosӨ In which:
D is the crystalline size in nm scale, λ is the wavelength of the X-rays (λ= 4 1.5416), k is the equilibrium constant of the equation and depends on the particle morphology (approximately equal to 0.89), β is the full-width at half-maximum (FWHM), and θ is the Bragg angle.
Injection of ZIONC
At first, normal saline was applied in preparing the investigated ZIONC suspension of the present study. Then, the diluted suspension was injected intraperitoneally using insulin syringes at doses of 1.25, 2.5, and 5 mg/kg/day for 12 days.
Studied animals (statistical community) and their care conditions
The study population of this study included 80 outbred adult male Wistar rats (220-250 g).
The studied rats were kept in conditions with an average temperature of 25 °C, the relative humidity of 55 %, and a light/dark cycle of 12:12. It should be noted that the rats had easy access to standard food and water.
Sampling and sampling methods
In this study, 80 male rats were divided into eight groups (n= 10 per group) as follows:
1. The control group (CO) that did not take the ZION treatment and noise stress.
2. Rat groups (Three groups) that were treated with ZION at doses of 1.25, 2.5, and 5 mg/kg/d for 12 days while were not exposed to noise stress (CO+N1.25, CO+N2.5, and CO+N5).
3. Stress group (ST): Rats that were received normal saline and were exposed to noise stress for 12 days (from 8 AM to 12 o'clock for 2 hours).
4. Rat groups (Three groups) that were exposed to noise stress for 12 days (from 8 AM to 12 o'clock for 2 hours) and were received different doses of 1.25, 2.5, and 5 mg/kg/day at the beginning noise stress until the MWM test (ST+N1.25, ST+N2.5, and ST+N5).
Noise protocol
At first, the sound caused by traffic in one of the busiest squares of the Kashan city was recorded by a standard audio recorder to investigate the effects of noise stress in experimental animals. Then, its intensity was set equal to 95 decibels using sonar software (version 8.5). Next, a small speaker has placed at a distance of 30cm from the cage floor in the middle of the animal cage (a metal-reflective chamber with dimensions of 60 × 60 × 60 cm) to apply the recorded sound.
Also, the sound intensity was monitored throughout the study using a sound level meter to apply noise stress with the same sound intensities according to the experimental treatments. On the other hand, although the recorded sound covered a wide range of audio frequencies, just annoying noises were considered here. Also, all study groups received sound (noise) stress at a specific hour (according to experimental treatments) every day (22).
Behavioral test
MWM test was used for evaluation of spatial learning and memory. The water maze
comprised of a circular tank (140 cm diameter, 60 cm high, and 40 cm deep and filled with 22±1°C water). The MWM test was performed in a room with indirect lighting with an optimal number of surrounding cues. A hidden square black platform or escape platform (10 cm diameter) was submerged 1.5~2.0 cm beneath the water surface in the middle of the target quadrant of the pool.
Animal motions were recorded and data were sent to a computer via a camera fixed above the center of the maze. Commercial software (version: 6 XT, Noldus Information Technology, Wageningen, The Netherlands) was used to measure the escape latency, distance travelled, swimming speed, and the number of crossings to the target quadrant during training and probe trials.
Spatial learning phase
Each training trial consisted of 4 trials per day for 3 consecutive days. In each trail, rats were gently released from the start position in the maze North (N), South (S), West (W), and East (E) at the middle of the circular edge of a randomly selected quadrant, with their noses pointed toward the wall. Rats were allowed to swim for a maximum duration of 60 s to find the hidden platform, with an inter-trial interval of 10 min. The mean latency time to find the hidden platform of the water maze task was recorded on each day of testing. If the animal failed to find the platform within 90 s, it was gently guided onto the platform. After completion of training, the animals were returned to their home cages until retention testing (probe trial) 24 h later.
Probe trial test (retention testing)
The probe trial test was performed on day 5, 24 h after the last acquisition day. In the probe test, the platform was removed and the rats was placed in the start position (S in this study) facing the maze wall, as in previous days. Finally, the animals were removed after 60 s circulating the tank searching for the platform. In probe test, the time spent searching, the traveled distance, the swimming speed in the target quadrant and the number of crossings to target quadrant were recorded.
Statistical analysis
The data were analyzed by SPSS (ver 20) and Two-way analysis of variance and Post hoc Tukey's test used at p< 0.05 to compare the mean of the data.
Ethical considerations
This paper has tried to perform ethical considerations in animal experiments by the ethical considerations of the Kashan University of Medical Sciences. Accordingly, the studied animals had access to adequate food and water, and the lowest possible number of animals was also employed in this study.
Results
Investigating anxiety
The results of the Two-way analysis of variance and Post hoc Tukey's test showed that sound stress had significant effects on the parameters assessed between the control and the on learning and spatial memory groups in rats in MWM (F7, 56= 3.123; P< 0.001).
Examination of the data obtained from the animal learning training sessions in the Mauritius water maze shows that the studied animals gradually recognized the location of the hidden platform using the spatial keys in the laboratory, as well as the location of the operator. They spend less to find the hidden platform and therefore travel less distance.
Analysis of the data obtained from the first stage of the Morris water maze between the control and stress groups indicates that the two groups in terms of time elapsed, (F7,3689=19.105;
P< 0.095)and distance traveled (F7,3689 = 13.336; P <0.102) to find the hidden platform inside the maze are not significantly different. The results showed that the injection of zinc / iron oxide nanocomposites in all three doses had no effect on the learning of animals in the nano-receiving control groups, so that there was a significant difference between the groups receiving three doses of zinc / iron oxide nanocomposites with the control group in terms of elapsed time and distance traveled. Was not found to find the hidden platform.Also, as shown in the figure, no significant differences were observed between the control groups and the nano-receiver stress.
Figure 1. Time elapsed to find the hidden platform (seconds) in the MWM
The results show that the injection of all three doses of zinc / iron oxide nanocomposites in the nano-receiving stress group had no effect on improving animal learning in terms of time spent finding the hidden platform and therefore had no effect on improving animal learning.
0 10 20 30 40 50 60
first day second day third day
Time elapsed to find the hidden platform (seconds) CO
ST
CO+N 1.25 CO+N 2.5 CO+N 5 ST+N 1.25 ST+N 2.5 ST+N 5
Figure 2. Mileage to find hidden platform (cm) in the MWM
The results show that the injection of all three doses of nanocomposites in the stress group receiving the nano had no effect on the distance traveled to find the hidden platform. At the end of the learning phase experiments, a probe test was performed by removing a hidden platform. The results of this experiment showed that the two groups of control and stress in terms of time spent and distance traveled in the quarter of the platform location were significantly different (P <0.001).
Statistical analysis of data obtained from the control group receiving zinc / iron oxide nanocomposites shows that there is no significant change in animal memory compared to the control group.Significant values for the control group receiving a dose of 1.25 mg / kg were equal to P = 0.089, for the control group receiving a dose of 2.5 mg / kg was equal to P = 0.246 and for the group receiving a dose of 5 mg / kg was equal to P = 0.094. Also, injection of zinc / iron oxide nanocomposites into stressed animals had no significant effect on memory improvement compared to the stress group. Significant values obtained from statistical analyzes for the stress group receiving a dose of 1.25 mg / kg equal to P = 0.176, for the stress group receiving a dose of 2.5 mg
0 200 400 600 800 1000 1200
first day second day third day
Mileage to find hidden platform (cm)
CO ST
CO+N 1.25 CO+N 2.5 CO+N 5 ST+N 1.25 ST+N 2.5 ST+N 5
/ kg equal to P = 0.541 and for the group receiving a dose of 5 mg / kg Equivalent to P = 0.071.
Analysis of the data obtained from this step did not show a significant difference between the control groups and the nano-receiving stress in all three doses of zinc / iron oxide nanocomposites.
Figure 3. Time spent in the quarter where the platform is located in the probe stage.
The diagram shows that injection of all three doses of zinc / iron oxide nanocomposites had no effect on improving the memory of animals under sound stress. However, injection of all three doses of zinc / iron oxide nanocomposites has impaired memory in controlled animals.
0 5 10 15 20 25 30
CO ST CO+N 1.25 CO+N 2.5 CO+N 5 ST+N 1.25 ST+N 2.5 ST+N 5 Time elapsed in a quarter of the platform location (seconds)
Studied groups
Figure 4.The distance traveled in a quarter of the platform at the probe stage
The results show that injection of all three doses of zinc / iron oxide nanocomposites had no effect on improving the memory of sound-stressed animals. On the other hand, injection of all three doses of zinc / iron oxide nanocomposites has impaired memory in controlled animals.
Results obtained from the synthesis of ZIONC
In the nanocomposite synthesis section of the present study, ZIONC was first synthesized and characterized according to the modified sol-gel technique. The obtained XRD pattern also showed that ZIONC was formed in three phases of ZnFe2O4, Fe2O3, Fe3O4 based on the standard picklists so that the mentioned phases created different peaks in 2Ө around 30, 35, 57, and 63°
(Figure 5).
0 50 100 150 200 250
CO ST CO+N 1.25 CO+N 2.5 CO+N 5 ST+N 1.25 ST+N 2.5 ST+N 5
Distance traveled in a quarter of the platform (cm)
Study groups
Figure 5. XRD template for the synthesized ZIONC
The TEM image taken from ZIONC (see the colored areas in figure 6) indicates the formation of a two-phase structure and a two-component composite derived from iron and zinc salts. Also, the synthesized plate-structured nanocomposite is observed in a range sizes of about 20 to 60 nm.
Figure 6. Transmission electron microscope (TEM) image of the synthesized ZIONC
The plate-like structure of ZIONCs (synthesized by the green chemistry method) is clearly shown in the image obtained by the SEM technique. Since SEM is an analysis method to determine the morphology of particles' surface, figure 7 displays the contrast differences of the atomic number of the multiphase of the ZIONC, which confirms the formation of the composite structure
of the synthesized product.
Figure 7. Scanning electron microscope (SEM) image from the synthesized ZIONC
Discussion
Analysis of the data obtained from the first stage of the Morris water maze between the control and stress groups indicates that there is no significant difference between the control and stress groups in terms of time elapsed and distance traveled to find the hidden platform. The results showed that the injection of zinc / iron oxide nanocomposites in all three doses had no effect on the learning of the animals in the control group so that there was no significant difference with the control group in terms of time elapsed and distance traveled to find the hidden platform. Also, injection of different doses of zinc / iron oxide nanocomposites had no effect on improving learning in stress group animals. Statistical analysis of the obtained data shows that the injection of zinc / iron oxide nanocomposites in all three doses to the stress group animals had no effect on reducing the time and distance traveled to find a hidden platform compared to the stress group animals.There was also no significant difference in animal learning between the control and stress groups receiving all three nanocomposite doses. As mentioned in the introduction, increased oxidative stress may be one of the reasons for the induction of cognitive impairments, learning and spatial memory. Studies have shown that oxidative stress may act as an inhibitory factor in the brain and affect specific brain functions related to cognitive and motor capacity.
Further evidence suggests that lower levels of intracellular oxidized protein increase cognition (23).
From the studies of this study, it can be seen that exposure to sound stress has significant effects on brain function, motor function and cognitive function, including spatial memory.
Increased release of reactive oxygen species is likely to be responsible for reduced spatial learning and memory in stress group animals and control group animals receiving zinc / iron oxide nanocomposites. Future research should be used to evaluate neurochemical mechanisms, behavioral effects, and environmental and potential nutritional protocols to reduce the risks of the effects of zinc / iron oxide nanocomposites with emphasis on cognitive and psychological components.(23)Thus, in line with previous studies, this study found that increasing vocal stress as an oxidative stress can reduce the level of learning and spatial memory in rats.In confirmation of the results of the present study on the impairment of learning and spatial memory following exposure to sound stress, we can mention some results in studies that sound stress on the neuroendocrine system to the characteristics of sound and noise (intensity and frequency), duration Exposure depends on the age and sex of the animal (24).Lemaire et al. Stated that impaired spatial learning is due to disruption of the HPA axis, and ultimately this inefficiency can lead to a decrease in granular neurons and neurogenesis in the hippocampus (25). Hippocampal glucocorticoid receptors are very sensitive to increased levels of these hormones, and high levels of these hormones can damage neurons in this area of the brain (26).The results of several other studies examining the exposure to different types of stress such as motor, social and injectable stress (27) also confirm the present study. Injection of zinc / iron oxide nanocomposites had no effect on learning but weakened spatial memory.
According to previous studies by researchers, iron overload (FeSO4) of (28) mg / kg caused a spatial memory defect in the radial maze behavioral test. Iron overload reduced locomotor activity and exploratory activity in rats (29). Iron is involved in a wide range of biochemical processes in the brain, and the brain contains high concentrations of ferrous iron (Fe2 +). Most neurons contain a full range of process iron proteins, including transferrin receptor (TFR), ferroprotein (FPN), divalent metal transporters, and iron-regulating proteins (IRP 1 and IRP 2), yet iron metabolism in the brain is well understood. Has not been.. Evidence has shown that the regional distribution of iron in the brain is heterogeneous and it was found that iron overload does not affect synaptic transitions and also does not affect memory and spatial learning (30).In fact, hippocampal disorders impair spatial learning and memory (31). Iron deficiency in the early stages of development causes irreversible damage to the structure and function of the brain (32).The CA3 region of the hippocampus is involved in recognizing patterns and spatial position; The CA1 region
is involved in short- and medium-term memory and temporal pattern separation (33).Both areas are involved in signaling the presence of animals in specific areas of space (34). Dentate gyrus (DG) is thought to play an important role in spatial information processing (33) and subiculum plays a role in memory retrieval and spatial encryption (35). The amount of transferrin in the brain increases when there is less iron in the cortex and areas of CA1 and the dentate gyrus of iron- containing cells. According to this study, the level of spatial memory scores is directly related to the amount of iron in the cells of the hippocampus and shows that iron is essential for the development and normal functioning of brain structures in memory and learning (36).Also in the study of the effect of zinc on learning and spatial memory, in a study it was stated that dietary supplements containing iron and zinc, improve learning and spatial memory and also have a significant effect on motor activity. Severe zinc deficiency in adult mice causes damage to the hippocampus and affects its function. . Memory impairments have been widely associated with zinc deficiencies. Young and old mice with zinc deficiency have also been shown to have poorer spatial memory. Due to the high concentration of this element. ZnO nanoparticles lead to cytotoxicity through the production of reactive oxygen species, oxidative damage, inflammation stimulation, and cell death. Exposure to zinc vapor may have adverse effects on cognition and memory, which are age- and sex-dependent. Due to the contradictory effects of zinc nanooxide in behavioral experiments related to cognitive processes, memory and learning to identify the mechanism of their effect is difficult.
Synthesis of ZIONC
In general, the obtained results of the XRD analysis showed that the intensity of the peaks of the synthesized ZIONC was lower than the peak intensity for the bulk state analysis. The expanding of the base of the peaks indicates nanoscale structures for the synthesized ZIONC. The size of the synthesized crystallite was estimated equal to 20 nm using the Debye‐Scherrer equation. Also, a comparison of the obtained XRD pattern with standard picklists and previous works for different pattern peaks in 2Өs around 30, 35, 42, and 58° showed that ZIONC was formed in the ZnFe2O4 phase (37). Here, the characterization of the synthesized ZIONC surface was detected using SEM images (5). ZIONC disk and plate structures are clearly defined in the obtained SEM images. According to the obtained a, b, c, and d regions in figure 4 and the contrast of the atomic number (Z-contrast), it can be observed that the brightest and darkest phases
indicated the highest and lowest atomic numbers, respectively. Hence, the above results confirm the multiphase structure of the XRD pattern. According to the nanostructured synthesis technique and raw materials used in the present study, a maximum of four phases ZnFe2O4, Fe3O4, Fe2O3, and ZnO were identified with molecular masses of 241, 231, and 159 g/mol. On the other hand, it was found that regions α and b are closer to the ZnFe2O4 phase through examining the XRD pattern and the proximity of the molar masses of the two phases of ZnFe2O4 and Fe3O4 with the numbers of 241 and 231. Besides, regions c and d may correspond to the Fe2O3 and ZnO phases.
Therefore, according to the above evidence, it can be recognized that the powder synthesized by the modified cell-gel technique is a multiphase nanocomposite consisting of zinc and iron oxides.
TEM images are a well-known analysis in determining the structure of nanocomposites. The amalgamation of different phases of nanocomposite formations, as a primary condition of a nanostructure formation, is detected by the electron beam passage from the structure of nanoparticles and nanopowders. The results in figure 4 (Atomic Number Contrast Technique) showed that at least two mixed phases were formed in regions α and b.
The standard sol-gel process is a wet-chemical technique that uses solvents, such as ethanol and molecular precursors (usually metal alkoxide), toward synthesizing various types of nanostructures, especially metal oxide nanoparticles. In this study, natural gelatin was applied as a gelling and coating agent. Also, water was used as a solvent, and simple mineral salts were used as precursors by removing expensive precursors of the Alkoxy group and alcohol solvent.
Therefore, the production of wastage in this method is reduced, which is known as an indicator in green chemistry and environmentally friendly chemical reactions, and less damage to the environment. Also, the speed of the process of converting sol to gel and, thus, the compaction speed of gel encourage using this method.
Laser Ablation Nanofilms technique is a proper method in the synthesis of different composites of zinc and iron oxides (38). Also, it is shown that Fe-ZnO nanocomposites are prepared using metal nitrate precursors by the application of coprecipitation and sonochemical methods (39, 40). Besides, the Fe3O4/ C/ ZnO three-component nanocomposite was obtained in some studies by a one-step sol-gel process, in which lignin amine (LA) was utilized as the carbon source and ligand donor agent (40).
Various mixtures of oxide nanocomposites, such as Fe2O3/ZnFe2O4, Fe2O3/ZnFe2O4/ZnO, and ZnFe2O4/Zn, were formed by a hydrothermal method via changing the molar ratios of iron and zinc salts and then calcination at 500 °C (41). In some studies, the coprecipitation technique was also employed to synthesize ZIONC using natural animal gelatin (pig skin gelatin) as a capping and ligand donor agent (42).
Conclusion
In the stress group, injection of three doses of zinc / iron oxide nanocomposites into
animals did not cause any improvement in the animal learning process. Acoustic stress disrupted the spatial memory of animals, and injections of all three doses of nanocomposites improved spatial memory in stressed animals.
Acknowledgment
This study was supported by Islamic Azad University Shahrekord Branch, Iran and Kashan University of Medical Sciences, Iran. Thanks are due to Dr. Mokhtar Panahi-Kalamuei from Institute of Nanoscience and Nanotechnology, University of Kashan, Iran for their laboratory supports.
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