الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
The amygdala is a complex nucleus present in the anterior part of temporal lobe. It is a part of the limbic system that has important role in complex memory, behavior and autonomic integration. The amygdala composed of nearly 13 nuclei. Diabetes mellitus is a global health problem and its global prevalence among adults has risen at the last years. Diabetes mellitus leads to damage in a number of tissues especially the brain. Maternal diabetes is regarded as a very important teratogen to brain of the offspring leading to congenital anomalies. Resveratrol is a type of natural phenol that is produced by several plants . Our study aimed to study the organization and development of amygdala in albino rats, in addition the effect of maternal induced diabetes on the development and cytoarchitecture of the amygdala nuclei in the offspring. In addition, the effect of induced diabetes on the cytoarchitecture of the amygdala nuclei in the adult rats was demonstrated. Furthermore the possible protective role of resveratrol was studied Our work involved two experiments: I-EXPERIMENT I (Developmental study): A total number of 40 adult female albino rats were used. They were divided into 4 subgroups Ia-Control group: 10 adult female albino rats received no treatment. Ib-Diabetic group: Diabetes was induced in the 10 female rats by using a single intraperitoneal injection of alloxan (150 mg/kg body weight). Ic-Resveratrol treated group: In this group 10 female rats received resveratrol orally from the first day of pregnancy and continued for 21 days (20 mg / kg body weight). Id-Resveratrol treated diabetic group: The diabetic rats received resveratrol orally (20 mg / kg body weight) from first day of pregnancy and through the whole duration of pregnancy and continued through the lactation period (for 21 days after delivery) At the end of the experiment the offspring were sacrificed at the following ages: 1 day (newborn), 10 day old rats and 21 day old rats. II- EXPERIMENT II (Adult group): In this experiment 72 adult male 4 month old rats were divided equally into 4 subgroups: IIa-Control group: 18 rats received no treatment. IIb- Diabetic group: Diabetes was induced to 18 adult rats by using a single intraperitoneal injection of alloxan (150 mg/kg body weight) IIc- Resveratrol treated group: 18 rats received resveratrol orally (20 mg / kg body weight) for 2 months then were sacrificed at the age of 6 months.
IId-Resveratrol treated diabetic group: The diabetic rats received resveratrol orally (20 mg / kg body weight) for 2 months then were sacrificed at the age of 6 months. At the end of the experiment adult rats were sacrificed at the age of 6 monthsAt the end of both experiments in all the studied groups, the rats were sacrificed. The brains were extracted from the skull. The region of the amygdala was dissected and it was processed for the following techniques: A-Light microscopic study: Gallocyanin stain. B-Electron microscopic study of the basolateral, central and medial nuclei. C-Immunohistochemical study: Caspase-3 and GABA. D-Molecular study: PPAR gamma expression in the 21 days old offspring of the control, diabetic and resveratrol treated diabetic mothers was evaluated. E-Morphometric study: Cell count in the lateral, basolateral, central and medial nuclei of amygdala was performed The results of our studies were as the following: In the control group, light microscopic examination revealed that the amygdala in different ages exhibited normal organization of different nuclei. In the newborn age, neurons within the different amygdala nuclei were small and densely packed. With increased age, neurons became larger with more developed nerve fibers. The ultrastructure of the neurons revealed euchromatic nuclei and surrounding cytoplasm was rich in organelles including free ribosomes mitochondria and rough endoplasmic reticulum. With increased age, the neurons exhibited more developed rough endoplasmic reticulum cisternae and mitochondria. Immunohistochemical staining using caspase-3 revealed negative to mild caspase-3 expression. Immunohistochemical staining using GABA revealed strong positive GABA expression. In diabetic groups of the four studied age groups, the light microscopic study revealed degenerative changes in neurons of various amygdala nuclei. Some neurons appeared with pyknotic nuclei or darkly stained nuclei. The ultrastructure of the neurons of this group revealed condensation of chromatin of the nuclei and the cytoplasm showed vacuolations, decreased free ribosomes, dilated rough endoplasmic reticulum and damaged mitochondria. Immunohistochemical staining using caspase-3 revealed strong caspase-3 expression. Immunohistochemical staining using GABA revealed decreased GABA expression. In the 21 days old offspring rats of the diabetic mothers there was decreased gene expression of PPAR gamma compared to that of the control group. The morphometric cell count revealed significant decrease in number of neurons compared to the control group.
In the resveratrol treated group of the four studied age groups, the light microscopic and morphometric studies of the studied nuclei were similar to those of the control group.
In the resveratrol treated diabetic group of the four studied age groups, the light microscopic study revealed the presence of few neurons with darkly stained nuclei in the various amygdala nuclei. The ultrastructure of neurons of this group revealed the presence of some vacuoles and mildly dilated rough endoplasmic reticulum in the cytoplasm of some neurons. Immunohistochemical staining using caspase-3 revealed decreased caspase-3 expression compared to the diabetic groups. Immunohistochemical staining using GABA revealed increased GABA concentration compared to the diabetic groups. In the 21 days old offspring rats of the resveratrol treated diabetic mothers there was increased gene expression of PPAR gamma compared to that of the diabetic group. Morphometric cell count revealed significant increase in cell number compared to the diabetic group.
Conclusion:
Diabetes mellitus causes degenerative changes to the amygdala and the maternal diabetes is linked to development of autism in the offspring. Resveratrol is an antioxidant that could protect the amygdala from the detrimental effect of diabetes mellitus. Resveratrol could protect the newborns as it crosses the placental barrier. It also could protect infants as it is excreted in milk. Resveratrol could be suggested in the treatment of autism. Finally, it could protect the amygdala in adults as it could cross the blood brain barrier.