A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of; Masters of Science in Medicine (Anatomical Sciences) School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg. 2017. / This research studied adult hippocampal neurogenesis in the dentate gyrus of the hippocampus of the Long-Evans rat. Eighteen male Long-Evans rats were exposed to complex enriched environment, the running wheel environment for exercise as single influencing factor and the standard laboratory environment for 28 days. Thereafter the rats were transcardially perfused with 0.9 normal saline followed by 4% paraformaldehyde. The brains were removed and frozen sagittal sections cut at 50 μm. Brain sections were stained with Cresyl violet for cytoarchitecture. Immunohistochemistry and immunofluorescence techniques were employed for the immature neurons with defined processes using the marker doublecortin (DCX), neuronal proliferation marker Ki-67, the synapse marker, synaptophysin and the dendritic spine marker, synaptobrevin. Giemsa staining was used to identify pyknotic neurons followed by counts for DCX, Ki-67, pyknotic positive cells, and volume density of the dentate gyrus. Results indicated a statistically significant increase in brain weight (p=0.5) for the complex enriched group when compared to the running group and control. The typical cytoarchitecture of the hippocampus in rodents was observed with more densely packed granule cell layer in the dorsal limb of the dentate gyrus compared to the ventral limb especially in the enriched group. The Ki-67 immunopositive cell number between groups showed a variable difference with a three-fold increase each between the standard control and exercise, and between the exercise and enriched but a six-fold increase between the standard control and the complex enriched groups. Comparing the DCX immunopositive results, we observed also that the neuronal numbers, structure, dendritic patterns as well as the neuronal arrangement on the dorsal and ventral limbs of the dentate gyrus varied significantly among groups. The apoptotic cell numberusing pyknotic cells, showed the standard control group to have the highest number of cells compared to the exercise versus the enriched group; noting a five-fold difference between the standard control and exercise, a twenty seven-fold difference between the standard control versus enriched and a twenty one-fold difference between 6 the exercise and complex enriched group. The volumetric analysis showed a 15-fold difference between the standard control and exercise groups, a five-fold difference between the exercise and complex enriched and a nineteen-fold difference between the standard control and complex enriched groups. However, no statistical significant difference was found in the volumetric analysis of the dentate gyrus between the groups. / MT2017

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When an organism is dehydrated, neurons in the Organum vasculosum lamina terminalis (OVL T) sense this variation in plasma osmolality (OSM) and excite magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) via glutamatergic synapses. The resulting action potential firing of MNCs will result in the secretion of vasopressin (VP) into the blood, which will promote water reabsorption from the kidney. The relationship between plasma VP and OSM (know as the VP-OSM ratio) is known to change in sensitivity during the course of a day. / Lorsqu'un organisme est déshydraté, les neurones dans l'Organum vasculosum lamina terminalis (OVL T) détectent le changement dans l'osmolalité du plasma (OSM) et excitent les cellules magnocellulaires neurosécrétoires (MNCs) dans le noyau supraoptique (SON) avec des synapses glutamatergique. La décharge des potentiels d'action qui survient dans les MNCs génère la sécrétion de vasopressine (VP) dans le sang, qui permettra la réabsorption d'eau au niveau du rein. Le rapport entre la VP et OSM (connu comme étant le rapport VP/OSM) subit des changements de sensibilité durant une journée.

Pup directed maternal licking and grooming (LG) increases with corticosterone (CORT) supplimentation (Rees et al 2004). Increases in LG lead to an attenuation of the adult offspring's HPA response to stress (Liu et aI1997). Similarly, Neonatal increases in glucocorticoids lead, in adulthood, to the same attenuation of the HPA stress response (Catalani et aI1993). We hypothesize that dams exhibiting increased LG will have increased circulating CORT, and this increase will be reflected in their offspring. This thesis characterizes the HPA hormone profile adrenocorticotropic hormone (ACTH), CORT & Corticosterone Binding Globulin (CBG) in High LG (H) and Low LG (L) litters, 5 days postpartum (P4). Furthermore pup plasma CORT levels are determined at (P) 3,4,6,10 & 14. Finally P10 Hand L LG ACTH, CORT & CBG will be assessed after stress. RESULTS: H compared to L LG dams have significantly increased plasma CORT (p=0.03). At P4, H LG offspring have significantly increased plasma CORT (p=0.03) and significantly decreased plasma ACTH (p=0.04) as compared to L LG offspring. Plasma CBG levels are significantly lower in H compared to L LG offspring (p=0.01) at the same age. Across the Stress Hyporesponsive Period (SHRP) H LG offspring had significantly increased plasma CORT (p= 0.00) compared to L LG offspring at P3. Challenged with a stressor at P10, H LG offspring have an exaggerated plasma CORT response (p=0.00). This data suggests increases in plasma CORT in the dams leads to increased CORT in the high offspring, contributing perhaps to a more mature stress response at P10. / Key word abbreviation: (1) CORT - CORTicosterone, (2) ACTH - AdrenoCorticoTropin releasing Hormone, (3) CBG - Corticosteroid Binding Globulin, (4) SHRP - Stress Hypo-Responsive Period, (5) P - Post-natal day, (6) HPA - Hypothalamic-Pituitary-Adrenal, (7) LG - Licking/Grooming, (8) ADX/OVX - ADrenalectomized/OVarectomized.

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