Effect of hypothyroidism on learning and memory in young rats

【Abstract】 Objective To investigate the effects of hypothyroidism ( hypothyroidism ) on learning and memory in young rats ( rats ) . A method of pregnant SD low copy female offspring model included in the study (n = 40), were male, 20 randomly selected from birth to the day of intraperitoneal injection T42 μ gP100g to weaning, T4 is a group substitution treatment, more than 20 A The low pups were not treated specially , and another 20 male rats in the normal control group were set up . A 50-day-old pups lower row and eight arms avoidance test, and compared with same day control treated group. RESULTS: The 50- day-old group of the hypothyroid mice had the highest number of errors in achieving the learning degree , and the memory latency was shortened after 24 hours . The difference was significant . The reference memory error in the eight-arm experiment of the 50- day-old A. Significant differences , increased working memory errors , significant differences , no significant differences in running maze time. Conclusion Hypothyroidism caused the decline of learning and memory ability of the pups.

[Key words] hypothyroidism ; young rats ; learning and memory thyroid hormone plays an important role in mammalian brain development , perinatal thyroid hormone deficiency will cause irreversible brain damage , causing severe sensation, movement disorders and mental retardation , And the onset time, severity and time to start thyroid hormone treatment are closely related to the occurrence and recovery of brain damage.

turn off. On the basis of previous studies on the apoptosis of hippocampal neurons in perinatal hypothyroidism ( hypothyroidism ) , we further used the dark-avoidance and eight-arm maze to detect learning and memory changes in the developmental hypothyroid.

Materials and Methods

An animal model and packet duplicator A low offspring model, SD male rats included in the study, numbers, random hypothyroid pups born on the same day from a daily intraperitoneal injection of thyroxine (T4) 2 μ gP100 g body weight to 21 days weaning as T4 replacement therapy group (20); I A low pups not special treatment (20); the normal control group of young rats (20). 21- day-old pups were weaned , and males were 3 to 4 per cage until the experiment. Free water , 12 hours of light per day ( lighting time : 8: 00 ~ 20: 00) . Room temperature 21 ± 2 °C , relative humidity 40% ~ 60% .

2 learning and memory research

211 Avoidance Test The 50- day-old experimental mice were tested . The SFK2 I type is divided into two types: clear and dark , with small doors communicating with each other ; the dark habit avoids the instinctive selection of the pups into the darkroom , and the pups entering the darkroom immediately suffer an electric shock (35 mV) and passively escape. Safe room. If you do not enter the darkroom for 5 minutes, you are considered to have completed the study . Record the number of times the pigs mistakenly enter the darkroom before completing the study , which mainly reflects the ability of the young rats to learn recently . After 24 hours , they are returned to the bright room again , and the rats are recorded by the bright room. The time of the dark room , which is the memory latency , mainly reflects the ability of the mice to remember in the near future.

212 Eight-arm Maze Experiment Test 50 (60) days old experimental mice. During the eight walls of the maze limit pups diet before the experiment, so that weight maintenance in 80% to 85% of free feeding body weight. Observations were made at 10: 00 to 17: 00 . Use a radial eight-arm ( four-arm food ) maze. The central area of ​​the labyrinth is 30 cm in diameter and extends eight arms (50 cm × 12 cm, surrounded by a wall of 415 cm ) at equal angles and equal lengths . The entire labyrinth is 40 cm above the ground . Before training pups to accommodate 2 d in the maze, once a day. When adapting, 3 to 4 pups were placed in the maze at the same time , free to move and ingest food for 10 min . Carried out once a day to adapt to training after a total of 10 d. In each training , only four of the eight arms were placed with food (Bio2Serv, Frenchtown, NJ, USA), arms 1 , 3 , 5, and 6 , respectively ; this sequence was maintained throughout the experiment. Pups on the central area of the maze, the central area at this time four weeks door shut, 15 s after the door was opened, choose to enter any offspring arm to food intake. The pups enter the arm with food and take the food for 1 correct selection , otherwise it is the wrong choice. Record the number of times the parameter was selected incorrectly. Re-entering the food arm is called working memory error (WME), and entering the food arm is called reference memory error (RME) .

3 statistical processing

Data analysis and processing was performed using SPSS 1010 for Windows statistical software. The data are expressed in x ± s . Groups, with the groups One2Way ANOVA or t-test for independent samples.

Result

1 Avoiding dark test Compared with the normal control group and the treatment group , the 50- day-old A-low group had more errors in achieving the learning level , the difference was very significant (P < 01001), and the treatment group had fewer errors than normal. The control group increased , but there was no statistical difference (P > 0105) . After 24 h , the memory latency of the hypothyroid mice was the shortest , and the difference was significant compared with the normal control and treatment groups (P <01001). The incubation period of the treatment group was shorter than that of the normal control group , but there was no statistical difference (P > 0105). ) , .

2 Eight-arm maze experiment Compared with the normal control and treatment group , there was no significant change in RME in the hypothyroid group (P < 0105); WME increased significantly (P > 0105); the total number of errors increased significantly (P < 0105); There was no significant difference in the total running maze time (P > 0105).

Discuss

Learning and memory are one of the advanced functions of the brain . Learning refers to the acquisition or development of experience ( behavioral habits, perceptions, thinking, etc. ) ; memory is the preservation and reproduction of experience. They are two different and closely related neuro-biological processes , on the one hand, the basis of thinking and cognition, and on the other hand, closely related to the sensory and motor functions of the brain ; this complex process at least involves the acquisition, consolidation and reproduction. Three main stages. Because of the comparability of learning and memory learning in humans , it is often used to study human learning and memory. At present, the overall level model from experimental animal studies of learning and memory abilities There are many shuttle box is one of them, because of its simple, fast, widely used in learning and memory experiments. In order to eliminate the influence of the rhythmic law of corticosteroid secretion on learning and memory , daily experiments were conducted at the same time. This experimental study found that the number of errors in entering the darkroom during the 50- day-old A. pupae increased , and the memory latency after 24 hours was shortened , indicating that the perinatal hypothyroidism affected the recent learning and memory ability of the pups. However, the use of electrical stimulation experiments in animals may cause excitement, anxiety, and that their amount of exercise and sensitivity to electrical stimulation and other non-animal learning and memory factors also affect the results. Animal studies spatial memory test is one of the most common methods of animal learning and memory, because the water maze test can effectively separate the animals space to identify with other capabilities, so previous studies hypothyroidism affect memory space of the offspring of more use of this method. However , the main indicator of the experiment is the time it takes for the animal to find a safe platform in the water maze (on-the- shelf latency ), which is closely related to the animal's motor function . Any drug that affects the animal's motor function and the state of the animal may affect the state. The results of this experiment. Thyroid hormones not only affect the nervous system , but also affect the development of skeletal muscles , which may affect the results of the test. In addition , the nature of the animal walking around the wall also limits its application. The eight-arm maze test is an animal that learns and memorizes the relative position of itself and the bait ( white snack pill placed at the end of the labyrinth arm ) by observing some fixed reference objects around it . This method can effectively exclude the animal due to its own motor dysfunction. affect learning and memory observed indicators, but also to isolate and analyze animal RME WME and at the same time. To this end , this experiment is the first to use the eight-arm maze to determine the spatial memory reproduction of perinatal hypothyroid rats. The study found that compared with normal controls and treated rats , WME of 50- day-old A. pupae increased , while RME did not change significantly. This separation of spatial memory can also be seen in the eight-arm maze test in which anticholinergic drugs reduce the acetylcholine content in rat hippocampal neurons . However, significant impairment of hippocampal function causes an increase in both WME and RME . Further research is needed on the spatial memory separation phenomenon and the specific mechanism in the A-low eight-arm test. Learning and memory are closely related to the synaptic structure and functional plasticity of the central nervous system. Thyroid hormone can affect the expression of various brain structural proteins and signal proteins , affect the proliferation, migration, differentiation, synapse development and myelination of nerve cells , affecting the transmission of information between neurons , leading to learning and memory. Such brain function is impaired. This study found that the learning and memory of the T4 replacement treatment in the post- natal T4 mice was significantly improved compared with the A. pupae , but the laboratory test results showed that this was a bacterial dysentery outbreak caused by Shigella contaminated water supply system. Of the 131 cases reported , 97 were students and 4 were teachers . Dietary survey by teachers and students of the school, did not find the relevant factors; students compare the incidence of drinking unboiled water, the incidence of water supply and other ways consistent with the incidence of water supply residents of the school population, the incidence of drinking unboiled water was significantly higher than students not to drink raw Water students , the water supply and the school, the incidence of residents is significantly higher than other residents of the water supply route ; through the school and residents water supply hygiene survey , found that school students and residents drinking tap water is not convenient for any disinfection treatment , and in the first One week before the onset of the disease , the management introduced the mountain water directly discharged into the reservoir into the reservoir , causing serious pollution to the pond water , which is the direct cause of the outbreak. In order to prevent the incidence and prevalence of intestinal infectious diseases, it suggested that government departments to rural areas "three and off" as an important part of the new rural construction, improve students' eating, drinking water, sanitation and achieve stool, safe disposal of waste, fundamentally Solve the practical problems in the prevention and treatment of intestinal infectious diseases.