Abstract
The purpose of the paper was to study changes in neurogenesis and functional state of the central nervous system in female mice С3Н-А predisposed to hormone-dependent tumors in experimental hypo- and hyperthyroidism. Methods. Experimental hyperthyroidism was modeled by intraperitoneal administration of L-thyroxine 50 ug/day and hypothyroidism by oral administration of propylthiouracil 0.4 mg/day for 40 weeks to female mice С3Н-А. Results. Chronic hypo- and hyperthyroidism was characterized by motor (motility) and emotional disorders in mice beginning with 18 day of the experiment, with preferable increase of quantitative indexes of all component of explorative activity and grooming in hyperthyroid mice and disturbance of explorative activity (decrease of hole reflex) in hypothyroid animals. Behavioral disorders was increasing progressively within the experiment (till 40 weeks). In hyperthyroid mice, the dopamine level in the cortex and hippocampus was elevated and in hypothyroid animals, the level and turnover of serotonin was reduced in the same structures of the brain. The changes in thyroid status of С3Н-А mice (hypo- and hyperthyroidism) effected on expression of neurogenesis and angiogenesis factors contradirectory. In hypothyroidism, the expression of GFAP and VEGF was reduced preferably with elevation of expression of PDGFR-α in the neocortex and hippocampus, and in hyperthyroidism, on the contrary, the expression of GFAP and VEGF was increased with decrease of PDGFR-α expressionin the same structures of the brain. In the cortex of С3Н-А mice with hyperthyroidism, the stable structural signs of strengthening the protein synthesized activity in the cytoplasm was observed, that was appeared with reduction of heterochromatin density in the nucleus, increase of polysomes number and hypertrophy of Golgi complex. At the same time, there were mediate signs of destruction of myelin fibers and disturbances in axon-spine synapses, capillarostasis and signs of dystrophic changes of endotheliocytes and perivascular space. In hypothyroidism, disorders involved myelin fibers preferably, spine apparatus and only slight changes of presynaptic terminals. Conclusion. Therefore, it is concluded on the base of behavioral, biochemical and morphological characteristics that hypothyroidism can provoke depressive state development. (For citation: Kozyrko EV, Glushakov PI, Shabanov PD. Behavioral, biochemical and morphological characteristics of experimentally changed thyroid status of female mice C3H-A. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):43-53. doi: 10.17816/RCF16143-53).
Highlights
Chronic hypo- and hyperthyroidism was characterized by motor and emotional disorders in mice beginning with 18 day of the experiment, with preferable increase of quantitative indexes of all component of explorative activity and grooming in hyperthyroid mice and disturbance of explorative activity in hypothyroid animals
The dopamine level in the cortex and hippocampus was elevated and in hypothyroid animals, the level and turnover of serotonin was reduced in the same structures of the brain
The expression of GFAP and VEGF was reduced preferably with elevation of expression of PDGFR-α in the neocortex and hippocampus, and in hyperthyroidism, on the contrary, the expression of GFAP and VEGF was increased with decrease of PDGFR-α expressionin the same structures of the brain
Summary
В процессе наблюдения за животными оценивали состояние и окрас шерсти по следующей шкале: 0 — серый с небольшой примесью коричневого; 1 — светло-коричневый; 2 — равномерно-коричневый (характерный для здоровых половозрелых самок мышей линии С3Н-А — агути); 3 — насыщенно-коричневый; 4 — насыщенно-коричневый с примесью черного; 5 — с выраженной черной окраской (меланисты). Через 4 месяца, после получения основных результатов эксперимента, по 20 половозрелых самок из каждой группы, намеченных для получения потомства P1, отсаживали в отдельные клетку и в течение 4–5 дней исследовали у них эстральный цикл методом цитологического анализа влагалищных мазков. После этого животных отсаживали до появления потомства в отдельные для каждой самки клетки. Для электронно-микроскопического исследования брали кусочки сенсомоторного отдела коры головного мозга мышей (I–V зоны), которые фиксировали в растворе 2,5 % глютарового альдегида на фосфатном буфере (рН 7,4). Критический уровень достоверности нулевой статистической гипотезы (об отсутствии значимых различий или факторных влияний) принимали равным 0,05
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