The impacts of diabetes in pregnancy on hippocampal synaptogenesis in rat neonates.

Diabetes during the pregnancy period impairs hippocampal development, and is associated with neurocognitive and neurobehavioral problems in the offspring. Synaptogenesis is one of the most important events in the development of the nervous system, and is known as a mechanism by which the memory process takes place. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles in the hippocampus involved also in learning and memory. The present study aimed to examine the effects of maternal diabetes on the expression and distribution pattern of SYP, as a marker of synaptogenesis, in the developing rat hippocampus using Immunofluorescence staining and real-time PCR. Wistar female rats were maintained as diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. Our results showed a significant down-regulation in mRNA expression of SYP in the offspring born to diabetic animals at P7, and P14 (P ⩽ 0.05 each). Regarding to the density of SYP expressing hippocampal neurons, we found a marked decrease in the distribution pattern of SYP in all hippocampal subfields of Streptozotocin (STZ)-D group rat neonates, especially in one and two weeks of age (P ⩽ 0.05 each). Moreover, the results revealed no significant changes in either gene expression or distribution pattern of SYP--positive neurons in insulin-treated group compared with the controls. The present study demonstrated that diabetes in pregnancy has negative impacts on synaptogenesis in the offspring's hippocampus. Furthermore, the rigid maternal glycaemia control by insulin treatment in most cases normalized these effects.

The distance of the sigmoid sinus and the middle fossa dura from the external auditory canal in chronic otitis media.

PURPOSE: Mastoid pneumatization is reduced in most patients suffering from chronic otitis media (COM). In most studies, the relationship between the degree of pneumatization and the distance of the sigmoid sinus from the external auditory canal has been examined, yielding different results. This study addresses the relationship between COM and the distance of the sigmoid sinus and also middle fossa dura from the external auditory canal. METHODS: This was a case-control study on 15 adult COM patients, 12 traumatic facial palsy patients, and 15 cadaver temporal bones. After mastoidectomy, the distance between the spine of Henle and both the middle fossa dura and sigmoid sinus were measured, and the findings in each group was analyzed using Tukey's and ANOVA tests. RESULTS: The average distance of the external auditory canal and the sigmoid sinus was 15.27 ± 3.3 mm in the COM group, 16.92 ± 3.23 mm in the traumatic facial palsy group, and 14.53 ± 2.92 mm in the cadaver temporal bones. There was no significant difference between the groups (p = 0.115). The average distance of the spine of Henle from the middle fossa dura was 6.73 ± 1.62 mm in the COM group, 11.4 ± 2.05 mm in the traumatic facial palsy group, and 8.93 ± 1.94 in the cadaver temporal bones. There was a significant difference between the groups (p < 0.001). CONCLUSION: The distance of both the sigmoid sinus and the middle fossa dura from the external auditory canal (which indicates mastoid pneumatization) is reduced in COM patients.

Diabetes mellitus type 1 induces dark neuron formation in the dentate gyrus: a study by Gallyas' method and transmission electron microscopy.

BACKGROUND: Diabetes mellitus type 1 is a chronic endogenous stressor. We investigated the effects of a diabetes mellitus type 1 on dark neuron formation in granular layer of dentate gyrus. MATERIALS AND METHODS: Diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (STZ) at a dose of 60 mg/kg dissolved in saline. Control animals were received only saline. In the end of eight weeks, the brains were removed and hippocampi studied by Gallyas' method and transmission electron microscopy. RESULTS: The comparison between the rate of dark neurons in diabetic group (223 ± 25) and of control (5.75 ± 4.34) showed significant level of difference (p<0.05). Ultrastructurally dark neurons showed apoptotic death criteria namely: dark and electron dense appearance, chromatin condensation, margination and clumping. CONCLUSIONS: Present results suggest that STZ-induced diabetes accelerates dark neuron formation with apoptotic criteria in granule layer of dentate gyrus.

The effect of repetitive spreading depression on neuronal damage in juvenile rat brain.

Spreading depression (SD) is pronounced depolarization of neurons and glia that travels slowly across brain tissue followed by massive redistribution of ions between intra- and extracellular compartments. There is a relationship between SD and some neurological disorders. In the present study the effects of repetitive SD on neuronal damage in cortical and subcortical regions of juvenile rat brain were investigated. The animals were anesthetized and the electrodes as well as cannula were implanted over the brain. SD-like event was induced by KCl injection. The brains were removed after 2 or 4 weeks after induction of 2 or 4 SD-like waves (with interval of 1 week), respectively. Normal saline was injected instead of KCl in sham group. For stereological study, paraffin-embedded brains were cut in 5 microm sections. The sections were stained with Toluidine Blue to measure the volume-weighted mean volume of normal neurons and the numerical density of dark neurons. The volume-weighted mean volume of normal neurons in the granular layer of the dentate gyrus and layer V of the temporal cortex in SD group were significantly decreased after four repetitive SD. Furthermore, densities of dark neurons in the granular layer of the dentate gyrus (after 2 weeks), the caudate-putamen, and layer V of the temporal cortex (after 4 weeks) were significantly increased in SD group. Repetitive cortical SD in juvenile rats may cause neuronal damage in cortical and subcortical areas of the brain. This may important in pathophysiology of SD-related neurological disorders.

Patterns of neurotransmitter receptor distributions following cortical spreading depression.

Spreading depression (SD), a self-propagating depolarization of neurons and glia, is believed to play a role in different neurological disorders including migraine aura and acute brain ischaemia. Initiation and propagation of SD modulate excitability of neuronal network. A brief period of excitation heralds SD which is immediately followed first by prolonged nerve cell depression and later by an excitatory phase. The aim of the present study was to characterize local and remote transmitter receptor changes after propagation of cortical SD. Quantitative receptor autoradiography was used to asses 16 transmitter receptor types in combined striatum-hippocampus-cortex slices of the rat 1 h after induction of cortical SD. In neocortical tissues, local increases of glutamate NMDA, AMPA, and kainate receptor binding sites were observed. In addition to up-regulation of ionotropic glutamate receptors, receptor binding sites of GABA(A), muscarinic M1 and M2, adrenergic alpha(1) and alpha(2), and serotonergic 5-HT(2) receptors were increased in the hippocampus. Cortical SD also upregulated NMDA, AMPA, kainate, GABA(A), serotonergic 5-HT(2), adrenergic alpha(2) and dopaminergic D1 receptor binding sites in the striatum. These findings indicate selective changes in several receptors binding sites both in cortical and subcortical regions by SD which may explain delayed excitatory phase after SD. Mapping of receptor changes by cortical SD increases our understanding of the mechanism of SD action in associated neurological disorders.