RESUMEN
Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common form of dementia, causing the loss of cognitive function. Our previous study has shown, using a doubly mutated mouse model of AD (APP/PS1), that the neural adhesion molecule L1 directly binds amyloid peptides and decreases plaque load and gliosis when injected as an adeno-associated virus construct (AAV-L1) into APP/PS1 mice. In this study, we microinjected AAV-L1, using a Hamilton syringe, directly into the 3-month-old APP/PS1 mouse hippocampus and waited for a year until significant neurodegeneration developed. We stereologically counted the principal neurons and parvalbumin-positive interneurons in the hippocampus, estimated the density of inhibitory synapses around principal cells, and compared the AAV-L1 injection models with control injections of green fluorescent protein (AAV-GFP) and the wild-type hippocampus. Our results show that there is a significant loss of granule cells in the dentate gyrus of the APP/PS1 mice, which was improved by AAV-L1 injection, compared with the AAV-GFP controls (p < 0.05). There is also a generalized loss of parvalbumin-positive interneurons in the hippocampus of APP/PS1 mice, which is ameliorated by AAV-L1 injection, compared with the AAV-GFP controls (p < 0.05). Additionally, AAV-L1 injection promotes the survival of inhibitory synapses around the principal cells compared with AAV-GFP controls in all three hippocampal subfields (p < 0.01). Our results indicate that L1 promotes neuronal survival and protects the synapses in an AD mouse model, which could have therapeutic implications.
RESUMEN
Introduction: There is an increasing evidence supporting the hypothesis that traumatic experiences during early developmental periods might be associated with psychopathology later in life. Maternal deprivation (MD) in rodents has been proposed as an animal model for certain aspects of neuropsychiatric disorders. Methods: To determine whether early-life stress leads to changes in GABAergic, inhibitory interneurons in the limbic system structures, specifically the amygdala and nucleus accumbens, 9-day-old Wistar rats were exposed to a 24 h MD. On postnatal day 60 (P60), the rats were sacrificed for morphometric analysis and their brains were compared to the control group. Results: Results show that MD affect GABAergic interneurons, leading to the decrease in density and size of the calcium-binding proteins parvalbumin-, calbindin-, and calretinin-expressing interneurons in the amygdala and nucleus accumbens. Discussion: This study indicates that early stress in life leads to changes in the number and morphology of the GABAergic, inhibitory interneurons in the amygdala and nucleus accumbens, most probably due to the loss of neurons during postnatal development and it further contributes to understanding the effects of maternal deprivation on brain development.
RESUMEN
There is scarce data in the contemporary literature regarding the correlation of the microanatomy of the perforating arteries, their atherosclerosis, and the ischemia in their territory. In order to examine, at least partially, those parameters, the perforating arteries of 12 brains were microdissected or their vascular casts were obtained. In addition, 30 specimens of the perforators were used for a histological and immunohistochemical study. Finally, radiological images of 14 patients with deep cerebral infarcts were examined following a selection among 62 subjects. It was found out that certain groups of the perforators ranged in number between 0 to 11 (1.1-8.4 on average). In addition to the origin from the parent vessels, some of the perforators also arose from the leptomeningeal branches. Occlusion of such a branch may result in both a superficial and a deep ischemic lesion. Besides, the common stems of certain perforators supplied both right and left portions of the corresponding brain regions. Occlusion of such a common trunk leads to bilateral infarction. The atherosclerosis of the perforating vessels, which was found in one third of the specimens, is the basis for the ischemic lesions development on their territory. Among the 62 patients with ischemic lesions, 14 had a deep cerebral infarcts, most often within the thalamus, as well as on the territory of the middle cerebral and the anterior choroidal artery perforators of the hemispheres. Our study showed that a strong correlation exists between certain microanatomical features, atherosclerosis, and region of supply of the perforating arteries, on the one hand, and location of the ischemic lesions on the other hand.