scholarly journals Long-Term Lead Exposure Since Adolescence Causes Proteomic and Morphological Alterations in the Cerebellum Associated with Motor Deficits in Adult Rats

2020 ◽  
Vol 21 (10) ◽  
pp. 3571 ◽  
Author(s):  
Luana Ketlen Reis Leão ◽  
Leonardo Oliveira Bittencourt ◽  
Ana Carolina Oliveira ◽  
Priscila Cunha Nascimento ◽  
Giza Hellen Nonato Miranda ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Motor Performance ◽  
Second Messengers ◽  
Motor Deficits ◽  
Proteomic Profile ◽  
Adult Rats ◽  
Morphological Alterations ◽  
Male Wistar Rats ◽  
Mature Neurons

Lead (Pb) is an environmental contaminant that presents a high risk for human health. We aimed to investigate the possible alterations triggered by the exposure to Pb acetate for a long period in motor performance and the possible relationship with biochemical, proteomic and morphological alterations in the cerebellum of rats. Male Wistar rats were exposed for 55 days, at 50 mg/Kg of Pb acetate, and the control animals received distilled water. Open field (OF) and rotarod tests; biochemistry parameters (MDA and nitrite); staining/immunostaining of Purkinje cells (PC), mature neurons (MN), myelin sheath (MS) and synaptic vesicles (SYN) and proteomic profile were analyzed. Pb deposition on the cerebellum area and this study drove to exploratory and locomotion deficits and a decrease in the number of PC, MN, SYN and MS staining/immunostaining. The levels of MDA and nitrite remained unchanged. The proteomic profile showed alterations in proteins responsible for neurotransmitters release, as well as receptor function and second messengers signaling, and also proteins involved in the process of apoptosis. Thus, we conclude that the long-term exposure to low Pb dose promoted locomotion and histological tracings, associated with alterations in the process of cell signaling, as well as death by apoptosis.

scholarly journals Lead-Induced Motor Dysfunction Is Associated with Oxidative Stress, Proteome Modulation, and Neurodegeneration in Motor Cortex of Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Luana Ketlen Reis Leão ◽  
Leonardo Oliveira Bittencourt ◽  
Ana Carolina Alves Oliveira ◽  
Priscila Cunha Nascimento ◽  
Maria Karolina Martins Ferreira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Motor Cortex ◽  
Wistar Rats ◽  
Toxic Metal ◽  
Bioinformatic Analysis ◽  
Motor Dysfunction ◽  
Motor Deficits ◽  
Proteomic Profile ◽  
Adult Rats

Lead (Pb) is a toxic metal with great neurotoxic potential. The aim of this study was to investigate the effects of a long-term Pb intoxication on the global proteomic profile, oxidative biochemistry and neuronal density in motor cortex of adult rats, and the possible outcomes related to motor functions. For this, Wistar rats received for 55 days a dose of 50 mg/Kg of Pb acetate by intragastric gavage. Then, the motor abilities were evaluated by open field and inclined plane tests. To investigate the possible oxidative biochemistry modulation, the levels of pro-oxidant parameters as lipid peroxidation and nitrites were evaluated. The global proteomic profile was evaluated by ultraefficiency liquid chromatography system coupled with mass spectrometry (UPLC/MS) followed by bioinformatic analysis. Moreover, it was evaluated the mature neuron density by anti-NeuN immunostaining. The statistical analysis was performed through Student’s t -test, considering p < 0.05 . We observed oxidative stress triggering by the increase in malonaldehyde and nitrite levels in motor cortex. In the proteomic analysis, the motor cortex presented alterations in proteins associated with neural functioning, morphological organization, and neurodegenerative features. In addition, it was observed a decrease in the number of mature neurons. These findings, associated with previous evidences observed in spinal cord, cerebellum, and hippocampus under the same Pb administration protocol, corroborate with the motor deficits in the rats towards Pb. Thus, we conclude that the long-term administration to Pb in young Wistar rats triggers impairments at several organizational levels, such as biochemical and morphological, which resulted in poor motor performance.

scholarly journals Long-term effect of dietary α-linolenic acid or decosahexaenoic acid on incorporation of decosahexaenoic acid in membranes and its influence on rat heart in vivo

2007 ◽  
Vol 293 (4) ◽  
pp. H2296-H2304 ◽  
Author(s):  
Adey Ayalew-Pervanchon ◽  
Delphine Rousseau ◽  
Daniel Moreau ◽  
Patrick Assayag ◽  
Pierre Weill ◽  
...  
Keyword(s):  
Linolenic Acid ◽  
Dietary Intakes ◽  
Adrenergic Stimulation ◽  
Adult Rats ◽  
Chronotropic Response ◽  
Cardiac Membrane ◽  
Male Wistar Rats ◽  
Dha Enrichment

The present study was designed to evaluate whether long-term intake of dietary α-linolenic acid (ALA), supplied as whole grain-extruded linseed, can increase endogenous production of n-3 long-chain polyunsaturated fatty acids (FAs) in healthy adult rats and influence the heart rate (HR) and adrenergic response in the same way as docosahexaenoic acid (DHA)-rich diets. DHA enrichment was evaluated using FA analysis of tissue phospholipids after 8, 16, 24, and 32 wk of feeding in male Wistar rats randomly assigned to three dietary groups ( n = 8 in each group): a reference fat diet (RFD), an ALA-rich (ALA) diet, and a DHA-rich (DHA) diet. At 1 wk before the animals were killed, under anesthesia, HR was measured from ECG recordings during an adrenergic stimulation challenge ( n = 8). There was a significant increase of DHA in the cardiac membrane in the ALA group compared with the RFD group. DHA content in the cardiac membrane was ∼10% in the ALA group vs. 20% in the DHA group and 4% in the RFD group. The cardiac FA profile was established after 2 mo and remained essentially unchanged thereafter. Regardless of the diet, DHA in the heart decreased with age. Nevertheless, DHA content in the heart remained at >15% in the DHA group and remained greater in older rats fed the ALA diet than in younger RFD-fed rats. Basal HR decreased in the ALA group (395 ± 24.9 beats/min) to a level between that of the DHA and RFD groups (375 ± 26.4 and 407 ± 36.7 beats/min, respectively). Both n-3 dietary intakes contribute to enhancement of the chronotropic response to adrenergic agonist stimulation. Regulation of HR by neurohumoral mediators may be controlled by lower content of DHA, e.g., by a dietary supply of extruded linseed (ALA).

scholarly journals From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

2021 ◽  
Vol 23 (1) ◽  
pp. 111
Author(s):  
Leonardo Oliveira Bittencourt ◽  
Victória Santos Chemelo ◽  
Walessa Alana Bragança Aragão ◽  
Bruna Puty ◽  
Aline Dionizio ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Inorganic Mercury ◽  
Nervous System Development ◽  
Proteomic Profile ◽  
Mercury Toxicity ◽  
Adult Rats ◽  
Motor Functions ◽  
Proteomic Approach ◽  
Mercury Intoxication

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.

scholarly journals Hippocampal Impairment Triggered by Long-Term Lead Exposure from Adolescence to Adulthood in Rats: Insights from Molecular to Functional Levels

2020 ◽  
Vol 21 (18) ◽  
pp. 6937
Author(s):  
Ana Carolina Alves Oliveira ◽  
Aline Dionizio ◽  
Francisco Bruno Teixeira ◽  
Leonardo Oliveira Bittencourt ◽  
Giza Hellen Nonato Miranda ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Inhibitory Avoidance ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Neural Structure ◽  
Adult Rats ◽  
Functional Aspects ◽  
Male Wistar Rats ◽  
Trolox Equivalent ◽  
Reduced Density

Lead (Pb) is an environmental and occupational neurotoxicant after long-term exposure. This study aimed to investigate the effects of systemic Pb exposure in rats from adolescence to adulthood, evaluating molecular, morphologic and functional aspects of hippocampus. For this, male Wistar rats were exposed to 50 mg/kg of Pb acetate or distilled water for 55 days by intragastric gavage. For the evaluation of short-term and long-term memories, object recognition and step-down inhibitory avoidance tests were performed. At the end of the behavioral tests, the animals were euthanized and the hippocampus dissected and processed to the evaluation of: Pb content levels in hippocampal parenchyma; Trolox equivalent antioxidant capacity (TEAC), glutathione (GSH) and malondialdehyde (MDA) levels as parameters of oxidative stress and antioxidant status; global proteomic profile and neuronal degeneration by anti-NeuN immunohistochemistry analysis. Our results show the increase of Pb levels in the hippocampus of adult rats exposed from adolescence, increased MDA and GSH levels, modulation of proteins related to neural structure and physiology and reduced density of neurons, hence a poor cognitive performance on short and long-term memories. Then, the long-term exposure to Pb in this period of life may impair several biologic organizational levels of the hippocampal structure associated with functional damages.

scholarly journals Protein recycling and limb muscle recovery after critical illness in slow- and fast-twitch limb muscle

2019 ◽  
Vol 316 (5) ◽  
pp. R584-R593 ◽  
Author(s):  
Sebastien Preau ◽  
Michael Ambler ◽  
Anna Sigurta ◽  
Anna Kleyman ◽  
Alex Dyson ◽  
...  
Keyword(s):  
Critical Illness ◽  
Functional Disability ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
Limb Muscle ◽  
Fungal Cell ◽  
Hindlimb Muscles ◽  
Initial Reduction ◽  
Male Wistar Rats

An impaired capacity of muscle to regenerate after critical illness results in long-term functional disability. We previously described in a long-term rat peritonitis model that gastrocnemius displays near-normal histology whereas soleus demonstrates a necrotizing phenotype. We thus investigated the link between the necrotizing phenotype of critical illness myopathy and proteasome activity in these two limb muscles. We studied male Wistar rats that underwent an intraperitoneal injection of the fungal cell wall constituent zymosan or n-saline as a sham-treated control. Rats ( n = 74) were killed at 2, 7, and 14 days postintervention with gastrocnemius and soleus muscle removed and studied ex vivo. Zymosan-treated animals displayed an initial reduction of body weight but a persistent decrease in mass of both lower hindlimb muscles. Zymosan increased chymotrypsin- and trypsin-like proteasome activities in gastrocnemius at days 2 and 7 but in soleus at day 2 only. Activated caspases-3 and -9, polyubiquitin proteins, and 14-kDa fragments of myofibrillar actin (proteasome substrates) remained persistently increased from day 2 to day 14 in soleus but not in gastrocnemius. These results suggest that a relative proteasome deficiency in soleus is associated with a necrotizing phenotype during long-term critical illness. Rescuing proteasome clearance may offer a potential therapeutic option to prevent long-term functional disability in critically ill patients.

scholarly journals Long-term motor deficit in brain tumour surgery with preserved intra-operative motor-evoked potentials

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Davide Giampiccolo ◽  
Cristiano Parisi ◽  
Pietro Meneghelli ◽  
Vincenzo Tramontano ◽  
Federica Basaldella ◽  
...  
Keyword(s):  
Evoked Potentials ◽  
Brain Tumour ◽  
Evoked Potential ◽  
Corticospinal Tract ◽  
Motor Evoked Potentials ◽  
Motor Evoked Potential ◽  
Motor Deficit ◽  
Motor Deficits ◽  
Brain Tumour Surgery

Abstract Muscle motor-evoked potentials are commonly monitored during brain tumour surgery in motor areas, as these are assumed to reflect the integrity of descending motor pathways, including the corticospinal tract. However, while the loss of muscle motor-evoked potentials at the end of surgery is associated with long-term motor deficits (muscle motor-evoked potential-related deficits), there is increasing evidence that motor deficit can occur despite no change in muscle motor-evoked potentials (muscle motor-evoked potential-unrelated deficits), particularly after surgery of non-primary regions involved in motor control. In this study, we aimed to investigate the incidence of muscle motor-evoked potential-unrelated deficits and to identify the associated brain regions. We retrospectively reviewed 125 consecutive patients who underwent surgery for peri-Rolandic lesions using intra-operative neurophysiological monitoring. Intraoperative changes in muscle motor-evoked potentials were correlated with motor outcome, assessed by the Medical Research Council scale. We performed voxel–lesion–symptom mapping to identify which resected regions were associated with short- and long-term muscle motor-evoked potential-associated motor deficits. Muscle motor-evoked potentials reductions significantly predicted long-term motor deficits. However, in more than half of the patients who experienced long-term deficits (12/22 patients), no muscle motor-evoked potential reduction was reported during surgery. Lesion analysis showed that muscle motor-evoked potential-related long-term motor deficits were associated with direct or ischaemic damage to the corticospinal tract, whereas muscle motor-evoked potential-unrelated deficits occurred when supplementary motor areas were resected in conjunction with dorsal premotor regions and the anterior cingulate. Our results indicate that long-term motor deficits unrelated to the corticospinal tract can occur more often than currently reported. As these deficits cannot be predicted by muscle motor-evoked potentials, a combination of awake and/or novel asleep techniques other than muscle motor-evoked potentials monitoring should be implemented.

scholarly journals Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas

2021 ◽  
Author(s):  
Frederik Grosse ◽  
Stefan Mark Rueckriegel ◽  
Ulrich-Wilhelm Thomale ◽  
Pablo Hernáiz Driever
Keyword(s):  
Brain Tumor ◽  
Executive Function ◽  
Cognitive Function ◽  
White Matter ◽  
Cerebellar Nuclei ◽  
Motor Deficits ◽  
Deep Cerebellar Nuclei ◽  
Cerebellar White Matter ◽  
Lesion Symptom Mapping

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

Neurophysiologic Mapping of Thalamocortical Tract in Asleep Craniotomies: Promising Results From an Early Experience

2020 ◽  
Author(s):  
Mirela V Simon ◽  
Daniel K Lee ◽  
Bryan D Choi ◽  
Pratik A Talati ◽  
Jimmy C Yang ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Corticospinal Tract ◽  
Sensory Function ◽  
Motor Deficit ◽  
Motor Deficits ◽  
Central Sulcus ◽  
Postcentral Gyrus ◽  
Subcortical Stimulation ◽  
Subcortical Mapping

Abstract BACKGROUND Subcortical mapping of the corticospinal tract has been extensively used during craniotomies under general anesthesia to achieve maximal resection while avoiding postoperative motor deficits. To our knowledge, similar methods to map the thalamocortical tract (TCT) have not yet been developed. OBJECTIVE To describe a neurophysiologic technique for TCT identification in 2 patients who underwent resection of frontoparietal lesions. METHODS The central sulcus (CS) was identified using the somatosensory evoked potentials (SSEP) phase reversal technique. Furthermore, monitoring of the cortical postcentral N20 and precentral P22 potentials was performed during resection. Subcortical electrical stimulation in the resection cavity was done using the multipulse train (case #1) and Penfield (case #2) techniques. RESULTS Subcortical stimulation within the postcentral gyrus (case #1) and in depth of the CS (case #2), resulted in a sudden drop in amplitudes in N20 (case #1) and P22 (case #2), respectively. In both patients, the potentials promptly recovered once the stimulation was stopped. These results led to redirection of the surgical plane with avoidance of damage of thalamocortical input to the primary somatosensory (case #1) and motor regions (case #2). At the end of the resection, there were no significant changes in the median SSEP. Both patients had no new long-term postoperative sensory or motor deficit. CONCLUSION This method allows identification of TCT in craniotomies under general anesthesia. Such input is essential not only for preservation of sensory function but also for feedback modulation of motor activity.

scholarly journals Severe Corneal Morphological Alterations after Excimer Laser Surface Ablation for a High Astigmatism

2021 ◽  
pp. 492-496
Author(s):  
Anna M. Roszkowska ◽  
Giovanni W. Oliverio ◽  
Giuseppe A. Signorino ◽  
Mario Urso ◽  
Pasquale Aragona
Keyword(s):  
Excimer Laser ◽  
Corneal Stroma ◽  
Corneal Topography ◽  
Laser Surface ◽  
Slit Lamp ◽  
Slit Lamp Examination ◽  
Morphological Alterations ◽  
Surface Ablation ◽  
Confocal Images

We report long-term alterations of anterior corneal stroma after excimer laser surface ablation for a high astigmatism. The patient claimed progressive visual loss in his right eye (RE) during the last 3 years after bilateral laser-assisted subepithelial keratectomy (LASEK) surgery. His examination comprised visual acuity (UDVA and CDVA), slit-lamp examination, corneal topography and tomography, AS-OCT, and confocal microscopy. The UDVA was 0.1 in his RE and 1.0 in the left eye. The CDVA in the RE was 0.8. The slit-lamp examination showed a stromal lesion in the inferior paracentral corneal zone, with multiple vertical tissue bridges and severe thinning. Corneal topography and tomography showed central flattening with inferior steepening and severe alteration in elevation maps. AS-OCT showed void areas in the anterior stroma with thinning of the underlying tissue, and confocal images were not specific. In this case, progressive corneal steepening and thinning that manifest topographically as inferior ectasia occurred in correspondence to the singular stromal alterations after LASEK.

Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

1989 ◽  
Vol 123 (1) ◽  
pp. 83-91 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi
Keyword(s):  
Body Weight ◽  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Long Term Effects ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Accessory Sex Organs ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91

Sign in / Sign up

Export Citation Format

Share Document