Effects of Goldblatt hypertension on rats' hippocampal cholinergic system.

Background: The classical renin-angiotensin system (RAS) has an important role in the cardiovascular system and water homeostasis in the body. Recently, the existence of RAS with all of its components has been shown in the mammalian brain. RAS participates in many brain activities, including memory acquisition and consolidation. Since the cholinergic neurotransmission in the hippocampus is crucial for these functions, this study aims to evaluate the hippocampal angiotensin receptors (ATs) and choline acetyltransferase (ChAT) mRNA in the renovascular hypertensive rats in captopril- and losartan-treated hypertensive rats. Methods: The rats were randomly divided into four groups of eight animals; sham, Goldblatt two kidney one clip (2K1C) hypertensive rats and Goldblatt 2K1C hypertensive rats received 5 mg/kg captopril and Goldblatt 2K1C hypertensive rats received 10 mg/kg losartan. After 8 days of treatment, the rats were sacrificed and angiotensin-converting enzyme (ACE), ChAT, AT1, and AT2 receptor mRNAs in the hippocampus of rats were assessed by real-time PCR. The Morris water maze test was applied to measure the cognitive functioning of the rats. Results: Hypertensive rats showed impaired acquisition and memory function in the Morris water maze test. Treatment with ACE inhibitor (captopril) and AT1 receptor antagonist (losartan) reversed the observed acquisition and memory deficit in hypertensive rats. Overexpression of AChE, AT1, and AT2 and low expression of ChAT were noted in the hippocampus of rats with Goldblatt hypertension compared with that of the sham group. Treatment with captopril significantly reversed these changes, while treatment with losartan slightly reduced the mentioned effects. Conclusion: The memory-enhancing effect of captopril in renovascular hypertensive rats might lead to increased hippocampal ChAT expression.

The protective role of ascorbic acid on hippocampal CA1 pyramidal neurons in a rat model of maternal lead exposure.

Oxidative stress is a major pathogenic mechanism of lead neurotoxicity. The antioxidant ascorbic acid protects hippocampal pyramidal neurons against cell death during congenital lead exposure; however, critical functions like synaptic transmission, integration, and plasticity depend on preservation of dendritic and somal morphology. This study was designed to examine if ascorbic acid also protects neuronal morphology during developmental lead exposure. Timed pregnant rats were divided into four treatment groups: (1) control, (2) 100mg/kg ascorbic acid once a day via gavage, (3) 0.05% lead acetate in drinking water, and (4) 0.05% lead+100mg/kg oral ascorbic acid. Brains of eight male pups (P25) per treatment group were processed for Golgi staining. Changes in hippocampal CA1 pyramidal neurons' somal size were estimated by cross-sectional area and changes in dendritic arborization by Sholl's analysis. One-way ANOVA was used to compare results among treatment groups. Lead-exposed pups exhibited a significant decrease in somal size compared to controls (P<0.01) that was reversed by cotreatment with ascorbic acid. Sholl's analysis revealed a significant increase in apical dendritic branch points near cell body (P<0.05) and a decreased total dendritic length in both apical and basal dendritic trees of CA1 neurons (P<0.05). Ascorbic acid significantly but only partially reversed the somal and dendritic damage caused by developmental lead exposure. Oxidative stress thus contributes to lead neurotoxicity but other pathogenic mechanisms are also involved.

Postnatal development of masseteric motoneurons in congenital hypothyroid rats.

It has been known that an intact thyroid hormone is obligatory for the attainment of the normal masticatory function at the time of weaning. Following induced maternal thyroid hypo-function, the development of masseter motoneurons was determined at postnatal days 1, 7, 15 and 23 (weaning time), using retrograde transport of horseradish peroxidase (HRP) in the normal and hypothyroid pups. Based on the HRP labeling profile (strong and weak), the soma area of the masseteric labeled motoneurons was measured in each group. No significant morphological differences were observed at the end of the first week of life. On day 15, hypothyroid masseteric labeled motoneurons consisted of 76% small and 24% medium-sized neurons compared to 58% and 42% in normal pups, respectively. At the time of weaning (i.e., day 23) the number of large masseter motoneurons reached to 1/3 of normal value with few, short and disoriented dendrites in the hypothyroid pup. There was no statistically significant difference in the uptake of HRP from the neuromuscular junction. These results suggest that neonatal thyroid hormone deficiency considerably postponed the development of feeding behavior from sucking to chewing and biting.