RESUMO
Facial nerve injury in rats have been widely used to study functional and structural changes that occur in the injured motoneurons and other central nervous system structures related with sensorimotor processing. A decrease in long-term potentiation of hippocampal CA3-to-CA1 commissural synapse has recently been reported related to this peripheral injury. Additionally, it has been found increased corticosterone plasmatic levels, impairment in spatial memory consolidation, and hippocampal microglial activation in animals with facial nerve axotomy. In this work, we analyzed the neuronal morphology of hippocampal CA1 and CA3 pyramidal neurons in animals with either reversible or irreversible facial nerve injury. For this purpose, brain tissues of injured animals sacrificed at different postlesion times, were stained with the Golgi-Cox method and compared with control brains. It was found that both reversible and irreversible facial nerve injury-induced significant decreases in dendritic tree complexity, dendritic length, branch points, and spine density of hippocampal neurons. However, such changes' timing varied according to hippocampal area (CA1 vs. CA3), dendritic area (apical vs. basal), and lesion type (reversible vs. irreversible). In general, the observed changes were transient when animals had the possibility of motor recovery (reversible injury), but perdurable if the recovery from the lesion was impeded (irreversible injury). CA1 apical and CA3 basal dendritic tree morphology were more sensible to irreversible injury. It is concluded that facial nerve injury induced significant changes in hippocampal CA1 and CA3 pyramidal neurons morphology, which could be related to LTP impairments and microglial activation in the hippocampal formation, previously described.
Assuntos
Traumatismos do Nervo Facial , Ratos , Animais , Traumatismos do Nervo Facial/patologia , Nervo Facial , Axotomia , Células Piramidais/fisiologia , Hipocampo/fisiologia , Neurônios Motores , Dendritos/patologiaRESUMO
The ventromedial hypothalamic nucleus (VMH) is located in the tuberal region of the hypothalamus and is traditionally considered the satiety center. In obese Zucker rats, which express a mutation in the leptin receptor gene and exhibit obesity from the first weeks of life, the morphology of VMH neurons is unknown. In the present study, we found that the dendritic length of VMH neurons in obese Zucker rats was significantly shorter than that in Long Evans rats. This finding allows us to suggest that obese Zucker rats exhibit both neuronal metabolic alterations related to leptin and a reduction in the flow of information within the neuronal circuits in which the VMH nucleus participates to regulate foraging.
Assuntos
Dendritos/patologia , Neurônios/patologia , Obesidade/patologia , Núcleo Hipotalâmico Ventromedial/patologia , Animais , Forma Celular/fisiologia , Ratos , Ratos ZuckerRESUMO
The pro-oxidant compound okadaic acid (OKA) mimics alterations found in Alzheimer's disease (AD) as oxidative stress and tau hyperphosphorylation, leading to neurodegeneration and cognitive decline. Although loss of dendrite complexity occurs in AD, the study of this post-synaptic domain in chemical-induced models remains unexplored. Moreover, there is a growing expectation for therapeutic adjuvants to counteract these brain dysfunctions. Melatonin, a free-radical scavenger, inhibits tau hyperphosphorylation, modulates phosphatases, and strengthens dendritic arbors. Thus, we determined if OKA alters the dendritic arbors of hilar hippocampal neurons and whether melatonin prevents, counteracts, or reverses these damages. Rat organotypic cultures were incubated with vehicle, OKA, melatonin, and combined treatments with melatonin either before, simultaneously, or after OKA. DNA breaks were assessed by TUNEL assay and nuclei were counterstained with DAPI. Additionally, MAP2 was immunostained to assess the dendritic arbor properties by the Sholl method. In hippocampal hilus, OKA increased DNA fragmentation and reduced the number of MAP2(+) cells, whereas melatonin protected against oxidation and apoptosis. Additionally, OKA decreased the dendritic arbor complexity and melatonin not only counteracted, but also prevented and reversed the dendritic arbor retraction, highlighting its role in post-synaptic domain integrity preservation against neurodegenerative events in hippocampal neurons.
Assuntos
Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Melatonina/farmacologia , Ácido Okadáico/farmacologia , Oxidantes/farmacologia , Animais , Fragmentação do DNA , Dendritos/patologia , Imuno-Histoquímica , Fármacos Neuroprotetores/farmacologia , Organoides/efeitos dos fármacos , Oxirredução , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
RESUMEN: El trastorno del espectro autista (TEA) abarca un grupo de trastornos multifactoriales del neurodesarrollo caracterizados por una comunicación e interacción social deteriorada y por comportamientos repetitivos y estereotipados. Múltiples estudios han revelado que en el TEA existen disfunciones sinápticas, en la cual la morfología y función neuronal son sustratos importantes en esta patogenia. En esta revisión comentamos los datos disponibles a nivel de anormalidades neuronales en el TEA, enfatizando la morfología de las dendritas, espinas dendríticas y citoesquelo de actina. Las dendritas y espinas dendríticas, ricas en actina, forman la parte postsináptica de la mayoría de las sinapsis excitadoras. En el TEA, los datos obtenidos apuntan a una desregulación en el crecimiento y desarrollo dendrítico, así como una alteración en la densidad de las espinas dendríticas. Lo anterior, se ve acompañado de alteraciones en la remodelación y composición del citoesqueleto neuronal. Para comprender mejor la fisiopatología del TEA, es necesario mayor información sobre cómo los cambios morfofuncionales de los actores que participan en la sinapsis impactan en los circuitos y el comportamiento.
SUMMARY: Autism Spectrum Disorder (ASD) is a group of multifactorial neurodevelopmental disorders, characterized by impaired communication and social interaction skills, and by repetitive and stereotyped behaviors. Multiple studies report that there are synaptic dysfunctions in ASD, in which important substrates such as morphology and neuronal function are involved in this pathogenesis. In this review we discuss the data available at the level of neuronal abnormalities in ASD, and emphasize the morphological aspects of dendrites, dendritic spines, and actin cytoskeleton. Actin-rich dendrites and dendritic spines shape the postsynaptic part of the most excitatory synapses. In ASD, the data points to a dysregulation in dendritic growth and development, as well as an alteration in the density of dendritic spines. This is accompanied by alterations in the remodeling and composition of the neuronal cytoskeleton. In order to better understand the pathophysiology of ASD, further information is needed on how the elements of synaptic morphofunctional changes impact circuits and behavior.
Assuntos
Humanos , Dendritos/patologia , Transtorno do Espectro Autista/patologia , Citoesqueleto de Actina/patologia , Espinhas Dendríticas/patologia , Transtorno do Espectro Autista/fisiopatologiaRESUMO
Metabolic syndrome (MS) results from excessive consumption of high-calorie foods and sedentary lifestyles. Clinically, insulin resistance, abdominal obesity, hyperglycemia, dyslipidemia, and hypertension are observed. MS has been considered a risk factor in the development of dementia. In the brain, a metabolically impaired environment generates oxidative stress and excessive production of pro-inflammatory cytokines that deteriorate the morphology and neuronal function in the hippocampus, leading to cognitive impairment. Therapeutic alternatives suggest that phenolic compounds can be part of the treatment for neuropathies and metabolic diseases. In recent years, the use of Gallic Acid (GA) has demonstrated antioxidant and anti-inflammatory effects that contribute to neuroprotection and memory improvement in animal models. However, the effect of GA on hippocampal neurodegeneration and memory impairment under MS conditions is still unclear. In this work, we administered GA (20 mg/kg) for 60 days to rats with MS. The results show that GA treatment improved zoometric and biochemical parameters, as well as the recognition memory, in animals with MS. Additionally, GA administration increased hippocampal dendritic spines and decreased oxidative stress and inflammation. Our results show that GA treatment improves metabolism: reducing the oxidative and inflammatory environment that facilitates the recovery of the neuronal morphology in the hippocampus of rats with MS. Consequently, the recognition of objects by these animals, suggesting that GA could be used therapeutically in metabolic disorders that cause dementia.
Assuntos
Ácido Gálico/farmacologia , Hipocampo/efeitos dos fármacos , Síndrome Metabólica/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Catalase/efeitos dos fármacos , Catalase/metabolismo , Dendritos/efeitos dos fármacos , Dendritos/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação/metabolismo , Insulina/sangue , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively. METHODS: Hippocampal sections from drug-resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan-drebrin expression. Double-labeling immunofluorescences were performed to localize drebrin A-positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers. RESULTS: Compared to controls, TLE patients had increased pan-drebrin in all hippocampal subfields and increased drebrin A-immunopositive area in all hippocampal subfields but CA1. Drebrin-positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin-positive spines with VGlut1-positive puncta, but not with GAD65-positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin-immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin-immunopositive area in IML compared with OML. SIGNIFICANCE: Our results suggest that changes in drebrin-positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome.
Assuntos
Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Neuropeptídeos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Lobectomia Temporal Anterior , Região CA1 Hipocampal/metabolismo , Região CA2 Hipocampal/metabolismo , Região CA3 Hipocampal/metabolismo , Estudos de Casos e Controles , Dendritos/metabolismo , Dendritos/patologia , Giro Denteado/metabolismo , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Glutamato Descarboxilase/metabolismo , Hipocampo/patologia , Hipocampo/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Plasticidade Neuronal , Esclerose , Proteína Vesicular 1 de Transporte de Glutamato/metabolismoRESUMO
Hyperglycemia of diabetes mellitus causes damage at the vascular level, which at the renal level represents diabetic nephropathy. In this pathology, there is arterial hypertension. In addition, several reports suggest that hyperglycemia and arterial hypertension affect interneuronal communication at the level of dendritic morphology. We studied these changes in an animal model with streptozotocin-induced diabetes mellitus in the spontaneous hypertensive (SH) rat. Recent reports from our laboratory have demonstrated that cerebrolysin (CBL), a preparation of neuropeptides with protective and repairing properties, reduces dendritic deterioration in both pathologies, in separate studies. In the present study, we evaluated the effect of CBL using the animal model with hyperglycemia and arterial hypertension and assessed the dendritic morphology using a Golgi-Cox staining procedure. Our results suggest that CBL ameliorated the reduction in the number of dendritic spines in the PFC and hippocampus caused by hyperglycemia in the SH rat. In addition, CBL also increased distal dendritic length in the PFC and hippocampus in hyperglycemic SH rats. Consequently, the CBL could be a therapeutic tool used to reduce the damage at the level of dendritic communication present in both pathologies.
Assuntos
Aminoácidos/farmacologia , Hipocampo/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Aminoácidos/uso terapêutico , Animais , Dendritos/efeitos dos fármacos , Dendritos/patologia , Hipocampo/patologia , Hiperglicemia/complicações , Hipertensão/complicações , Fármacos Neuroprotetores/uso terapêutico , Córtex Pré-Frontal/patologia , Ratos , Ratos Endogâmicos SHRRESUMO
We previously found that fish oil (FO) facilitated memory recovery in the absence of pyramidal neuron rescue after transient, global cerebral ischemia (TGCI). Fish oil preserved the expression of microtubule-associated protein 2 (MAP-2), suggesting a relationship between dendritic plasticity and memory recovery that is mediated by FO after TGCI. The present study examined whether postischemic treatment with FO prevents ischemia-induced loss of dendritic processes in remaining pyramidal neurons. The effects of FO on neuroplasticity-related proteins were also examined after TGCI. Rats were subjected to TGCI (15 min, four-vessel occlusion model) and then received vehicle or FO (300 mg/kg docosahexaenoic acid) once daily for 7 days. The first dose was administered 4 h postischemia. Golgi-Cox staining was used to evaluate dentrict morphology in the pyramidal neurons of hippocampus (CA1 and CA3 subfields) and prefrontal cortex (PFC). Neuronal nuclei protein (NeuN), brain-derived neurotrophic factor (BDNF), growth-associated protein 43 (GAP-43), synaptophysin (SYP), and postsynaptic density protein 95 (PSD-95) levels were measured by Western blot in both structures. Fifteen minutes of TGCI reduced consistently the length of dendrites, number of dendritic branches and dendritic spine density (average of 25%, 43%, 32%, respectively) 7, 14, and 21 days postischemia, indicating that they did not recover spontaneously. This outcome of TGCI was reversed by FO treatment, an effect that was sustained even after treatment cessation. The NeuN and BDNF protein levels were reduced in both the hippocampus and PFC, which were recovered by FO treatment. GAP-43 protein levels decreased after ischemia in the PFC only, and this effect was also mitigated by FO. Neither SYP nor PSD-95 levels were altered by ischemia, but PDS-95 levels almost doubled after FO treatment in the ischemic group. These data support our hypothesis that synaptic plasticity at the level of dendrites may at least partially underlie the memory-protective effect of FO after TGCI and strengthen the possibility that FO has therapeutic potential for treating the sequelae of brain ischemia/reperfusion injury.
Assuntos
Dendritos/efeitos dos fármacos , Óleos de Peixe/farmacologia , Ataque Isquêmico Transitório/patologia , Plasticidade Neuronal/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Animais , Dendritos/patologia , Ácidos Docosa-Hexaenoicos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Wistar , Sinapses/patologiaRESUMO
Autism spectrum disorder (ASD) has been associated to atypical neuronal connectivity in the prefrontal cortex (PFC) and the hippocampus, in part, due to an alteration in neuroplasticity processes such as dendritic remodeling. Moreover, it has been proposed that abnormal cytoskeletal dynamics might be underlying the disrupted formation and morphology of dendrites in the ASD brain. Hence, we performed an analysis of the complexity of dendritic arborization of the pyramidal neurons localized in the layer II/III of the PFC and the CA1 region of the hippocampus in the autistic-like mouse strain C58/J, which has previously demonstrated neuronal cytoskeleton anomalies. We found differences in length, number and branching pattern of dendrites of the pyramidal neurons from both structures of C58/J strain. These data suggest a lower dendritic arborization complexity that could be involved with the characteristic autistic-like behaviors displayed in C58/J mice.
Assuntos
Transtorno do Espectro Autista/patologia , Dendritos/patologia , Hipocampo/patologia , Córtex Pré-Frontal/patologia , Células Piramidais/patologia , Animais , Camundongos EndogâmicosRESUMO
Rabies is a viral infection that targets the nervous system, specifically neurons. The clinical manifestations of the disease are dramatic and their outcome fatal; paradoxically, conventional histopathological descriptions reveal only subtle changes in the affected nervous tissue. Some researchers have considered that the pathophysiology of rabies is based more on biochemical changes than on structural alterations, as is the case with some psychiatric diseases. However, we believe that it has been necessary to resort to other methods that allow us to analyze the effect of the infection on neurons. The Golgi technique is the gold standard for studying the morphology of all the components of a neuron and the cytoskeletal proteins are the structural support of dendrites and axons. We have previously shown, in the mouse cerebral cortex and now with this work in spinal cord, that rabies virus generates remarkable alterations in the morphological pattern of the neurons and that this effect is associated with the increase in the expression of two cytoskeletal proteins (MAP2 and NF-H). It is necessary to deepen the investigation of the pathogenesis of rabies in order to find therapeutic alternatives to a disease to which the World Health Organization classifies as a neglected disease.