The present study investigated the long-lasting effects of prenatal repeated restraint stress on social behavior and anxiety, as well as its repercussions on oxytocin (OT) and vasopressin ...(VP)-positive neurons of the paraventricular (PVN) and supraoptic (SON) nuclei from stressed pups in adulthood. Female Wistar rats were exposed to restraint stress in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatally non-stressed offspring raised by prenatally non-stressed mothers (NS:NS), prenatally non-stressed offspring raised by prenatally stressed mothers (S:NS), prenatally stressed offspring raised by prenatally non-stressed mothers (NS:S), prenatally stressed offspring raised by prenatally stressed mothers (S:S). As adults, male prenatally stressed offspring raised both by stressed mothers (S:S group) and non-stressed ones (NS:S group) showed impaired social memory and interaction. In addition, when both adverse conditions coexisted (S:S group), increased anxiety-like behavior and aggressiveness was observed in association with a decrease in the number of OT-positive magnocellular neurons, VP-positive magnocellular and parvocellular neurons of the PVN. The NS:S group exhibited a reduction in the amount of VP-positive magnocellular neurons compared to the S:NS. Thus, the social behavior deficits observed in the S:S and NS:S groups may be only partially associated with these alterations to the peptidergic systems. No changes were shown in the OT and VP cellular composition of the SON nucleus. Nevertheless, it is clear that a special attention should be given to the gestational period, since stressful events during this time may be related to the emergence of behavioral impairments in adulthood.
Abstract Spinal cord injury (SCI) has very poor clinical prospects, resulting in irreversible loss of function below the injury site. Although applied in clinical trials, olfactory ensheathing cells ...transplantation (OEC) derived from lamina propria (OLP) is still a controversial repair strategy. The present study explored the efficacy of OLP or respiratory lamina propria (RLP) transplantation and the optimum period after SCI for application of this potential therapy. Adult male rats were submitted to spinal cord transection and underwent acute, 2-week or 4-week post-injury transplantation with pieces of OLP (containing OECs) or RLP (without OECs). After grafting, animals with OLP and RLP showed discrete and similar hindlimb motor improvement, with comparable spinal cord tissue sparing and sprouting in the lesion area. Acute transplantation of OLP and RLP seems to foster limited supraspinal axonal regeneration as shown by the presence of neurons stained by retrograde tracing in the brainstem nuclei. A larger number of 5-HT positive fibers were found in the cranial stump of the OLP and RLP groups compared to the lesion and caudal regions. Calcitonin gene-related peptide fibers were present in considerable numbers at the SCI site in both types of transplantation. Our results failed to verify differences between acute, 2-week and 4-week delayed transplantation of OLP and RLP, suggesting that the limited functional and axon reparative effects observed could not be exclusively related to OECs. A greater understanding of the effects of these tissue grafts is necessary to strengthen the rationale for application of this treatment in humans.
Summary
Knowledge of skeletal muscle adaptations is important to understand the functional deficits in cerebral palsy (CP). This study aimed to investigate the morphofunctional characteristics of ...skeletal muscle in a CP animal model. Initially, pregnant Wistar rats were injected intraperitoneally with saline or lipopolysaccharide over the last five days of pregnancy. The control group (n = 8) consisted of male pups born to females injected with saline. The CP group (n = 8) consisted of male pups born to females injected with lipopolysaccharide, which were submitted to perinatal anoxia day of birth, postnatal day 0 (P0) and sensorimotor restriction (P1‐P30). The open‐field test was undertaken on P29 and P45. On P48, the animals were weighed, and the plantaris muscle was collected and its weight and length were measured. Transverse sections were stained with haematoxylin‐eosin, NADH‐TR, Masson's trichrome and non‐specific esterase reaction for analysis. and transmission electron microscopy was performed. In the CP group, reductions were observed in mobility time, number of crossings and rearing frequency, body weight, muscle weight and length, and nucleus‐to‐fibre and capillary‐to‐fibre ratios. There was a statistically significant increase in the percentage area of the muscle section occupied by collagen; reduction in the area and increase in the number of type I muscle fibres; increase in myofibrillar disorganization and Z‐line disorganization and dissolution; and reduction in the area and largest and smallest diameters of neuromuscular junctions. Thus this animal model of CP produced morphofunctional alterations in skeletal muscle, that were associated with evidence of motor deficits as demonstrated by the open‐field test.
Rationale
Social instigation is used in rodents to induce high levels of aggression, a pattern of behavior with certain parallels to that of violent individuals. This procedure consists of a brief ...exposure to a provocative stimulus male, before direct confrontation with an intruder. Studies using 5-HT
1A
and 5-HT
1B
receptor agonists show an effective reduction in aggressive behavior. An important site of action for these drugs is the ventral orbitofrontal cortex (VO PFC), an area of the brain which is particularly relevant in the inhibitory control of aggressive and impulsive behavior.
Objectives
The objectives of the study are to assess the anti-aggressive effects of 5-HT
1A
and 5-HT
1B
agonist receptors 8-hydroxy-2-(di-
n
-propylamino) tetralin hydrobromide (8-OH-DPAT) and CP-93,129 in the VO PFC of socially provoked male mice. To confirm the specificity of the receptor, 5-HT
1A
and 5-HT
1B
antagonist receptors (WAY-100,635 and SB-224,289) were microinjected into the same area, in order to reverse the agonist effects.
Results
8-OH-DPAT (0.56 and 1.0 μg) reduced the frequency of attack bites. The lowest dose of CP-93,129 (0.1 μg) also decreased the number of attack bites and lateral threats. 5-HT1A and 5-HT1B receptor agonists differed in their effects on non-aggressive activities, the former decreasing rearing and grooming, and the latter, increasing these acts. Specific participation of the 1A and 1B receptors was verified by reversal of anti-aggressive effects using selective antagonists WAY-100,635 (10.0 μg) and SB-224,289 (1.0 μg).
Conclusions
The decrease in aggressiveness observed with microinjections of 5-HT
1A
and 5-HT
1B
receptor agonists into the VO PFC of socially provoked mice, supports the hypothesis that activation of these receptors modulates high levels of aggression in a behaviorally specific manner.
The middle ear is important from an anatomical and clinical point of view, seeing that it contains and allows the passages of structures, in addition to establishing relations with other regions of ...the head. However, the middle ear is small and difficult to dissect, making difficult the study in cadavers and understanding. In this context, professors and students from Universidade Estadual do Oeste do Paraná developed an anatomical model of themiddle ear, showing its main bones, membranes, muscles and nerves. The model was developed with acrylic plates joined to form a cube, each side representing one of the middle ear’s walls. The tympanic membrane and the secondary tympanic membrane were represented by an elastic fabric, which covered openings on the membranous wall and the labyrinthic wall, respectively. The auditory ossicles, the muscles and the nerves were made from polymer clay and positioned inside the cube, according to their characteristics and anatomicalposition in the middle ear. Furthermore, the auditory tube was represented by a plastic cone projecting from the carotid wall. The use of these low-cost anatomical models is an alternative to enable and improve learning. These initiatives favor the teaching of Human Anatomy, increasing understanding, the establishment of clinical correlations, and improving the academic education of health professionals.
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•Pre-natal infection, asphyxia and sensorimotor restriction alter gait pattern in rats.•Motor impairments were attenuated over time.•Sensorimotor cortex and dorsal striatum exhibited ...an increased number of glial cells.•White matter injury were not observed in this cerebral palsy animal model.•The interventions used did not affect soma area of motoneurons in the spinal cord.
In an attempt to propose an animal model that reproduces in rats the phenotype of cerebral palsy, this study evaluated the effects of maternal exposure to bacterial endotoxin associated with perinatal asphyxia and sensorimotor restriction on gait pattern, brain and spinal cord morphology. Two experimental groups were used: Control Group (CTG) − offspring of rats injected with saline during pregnancy and Cerebral Palsy Group (CPG) − offspring of rats injected with lipopolysaccharide during pregnancy, submitted to perinatal asphyxia and sensorimotor restriction for 30days. At 29days of age, the CPG exhibited coordination between limbs, weight-supported dorsal steps or weight-supported plantar steps with paw rotation. At 45days of age, CPG exhibited plantar stepping with the paw rotated in the balance phase. An increase in the number of glial cells in the primary somatosensory cortex and dorsal striatum were observed in the CPG, but the corpus callosum thickness and cross-sectional area of lateral ventricle were similar between studied groups. No changes were found in the number of motoneurons, glial cells and soma area of the motoneurons in the ventral horn of spinal cord. The combination of insults in the pre, peri and postnatal periods produced changes in hindlimbs gait pattern of animals similar to those observed in diplegic patients, but motor impairments were attenuated over time. Besides, the greater number of glial cells observed seems to be related to the formation of a glial scar in important sensorimotor brain areas.
•Maternal protein restriction was conducted during pregnancy and lactation.•Muscle fibers and neuromuscular junctions of offspring at 365 days old were analyzed.•Ultrastructure and three types of ...muscle fibers were altered in restricted animals.•Modifications in neuromuscular junctions and collagen were also observed.•Maternal protein restriction can affect neuromuscular system development.
Changes in the nutritional status of mothers may predispose their offspring to neuromuscular disorders in the long term. This study evaluated the effects of maternal protein restriction during pregnancy and lactation on the muscle fibers and neuromuscular junctions (NMJs) of the soleus muscle in the offspring of rats at 365 days of age that had undergone nutritional recovery. Wistar rats were divided into two groups: control (CG) – the offspring of mothers fed a normal protein diet (17%) and restricted (RG) – offspring of mothers fed a low protein diet (6%). After lactation, the male pups received standard chow ad libitum. At 365 days, samples of soleus muscle were collected for muscle fiber analysis (HE staining, NADH-TR reaction and ultrastructure), intramuscular collagen quantification (picrosirius red staining) and NMJs analysis (non-specific esterase technique). The cross-sectional area of type I fibers was reduced by 20% and type IIa fibers by 5% while type IIb fibers increased by 5% in the RG compared to the CG. The percentage of intramuscular collagen was 19% lower in the RG. Disorganization of the myofibrils and Z line was observed, with the presence of clusters of mitochondria in both groups. Regarding the NMJs, in the RG there was a reduction of 10% in the area and 17% in the small diameter and an increase of 7% in the large diameter. The results indicate that the effects of maternal protein restriction on muscle fibers and NMJs seem to be long-lasting and irreversible.
ABSTRACT
Introduction: A balanced maternal diet is a determining factor in normal fetal development. The objective of this study was to evaluate the effects of maternal protein restriction during ...pregnancy and lactation on muscle fiber and neuromuscular junction (NMJ) morphology of rat offspring at 21 days of age. Methods: Wistar rats were divided into a control group (CG), offspring of mothers fed a normal protein diet (17%), and a restricted group (RG), offspring of mothers fed a low‐protein diet (6%). After a period of lactation, the animals were euthanized, and soleus muscles were obtained from pups for analysis. Results: The soleus muscles of the RG exhibited an increase of 133% in the number of fibers and of 79% in the amount of nuclei. Moreover, the number of NMJs was lower in the restricted group than in the CG. Conclusions: Maternal protein restriction alters the normal development of the neuromuscular system. Muscle Nerve 55: 109–115, 2017
Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched ...environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic–pituitary–adrenal axis and microglial activation in diabetic animals.
In view of the increase in the prevalence of obesity and metabolic syndrome in childhood and adolescence, this study proposed the early and combined use of treatments to restore brain areas related ...to satiety. The vitamin D supplementation, aerobic exercise and the combination of these interventions on the structure of arcuate (ARC) and ventromedial (VMH) nuclei of hypothalamus were investigated in monosodium glutamate (MSG)-treated rats.
Wistar rats were separated into five groups: Control group (CT); Obese group injected with MSG (OB); Obese group supplemented with vitamin D (OBvd); Obese group submitted to forced swimming training (OBexe) and Obese group treated with vitamin D supplementation and forced swimming training (OBvd + exe).
In the OB group, the visceral fat weight was significantly higher, there was a reduction in the number of glial cells in the ARC nucleus and also in the number of neurons in the ARC and VMH nuclei. Aerobic exercise was able to reduce the visceral fat weight in the OBexe group. The combination of treatments used in the OBvd + exe group reversed the loss of neurons and glial cells produced by MSG in the ARC nucleus. All treated groups exhibited a higher number of neurons in VMH nucleus, but an increase in the glial cells were observed only in the OBexe and OBvd + exe groups.
The effectiveness of obesity treatment can be favored through the early and combined use of vitamin D supplementation and aerobic exercise, since these therapies are able to restore brain nuclei involved in the control of food intake.
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