ABSTRACT
Normal ageing results in brain selective neuronal and glial losses. In the present study we analyze neuronal and glial changes in Wistar rats at two different ages, 45 days (young) and 420 days (mature adult), using Nissl staining and glial fibrillary acidic protein (GFAP) immunohistochemistry associated to the Sholl analysis. Comparing mature adults with young rats we noted the former present a decrease in neuronal density in the cerebral cortex, corpus callosum, pyriform cortex, L.D.D.M., L.D.V.L., central medial thalamic nucleus and zona incerta. A decrease in glial density was found in the dorsomedial and ventromedial hypothalamic nuclei. Additionally, the neuron/glia ratio was reduced in the central medial thalamic nucleus and increased in the habenula. No changes were found in the neuronal and glial densities or neuron/glia ratio in the other studied regions. The number of astrocytic primary processes and the number of intersections counted in the Sholl analysis presented no significant difference in any of the studied regions. Overall, neither GFAP positive astrocytic density nor GFAP immunoreactivity showed alteration.
Subject(s)
Aging/metabolism , Brain/metabolism , Glial Fibrillary Acidic Protein/metabolism , Neuroglia/metabolism , Neurons/metabolism , Aging/pathology , Animals , Brain/pathology , Male , Neuroglia/pathology , Neurons/pathology , Rats , Rats, WistarABSTRACT
It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca2+]i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats.
Subject(s)
Long-Term Potentiation/drug effects , Memory/drug effects , Methylprednisolone/pharmacology , Animals , CA1 Region, Hippocampal/drug effects , Calcium/metabolism , Hippocampus/drug effects , Male , Memory/classification , Memory/physiology , Methylprednisolone/metabolism , Rats , Rats, Wistar , Synapses/physiologyABSTRACT
Approximately 30% of patients with mesial temporal lobe epilepsy do not respond to treatment with antiepileptic drugs. We have previously shown that transplantation of mononuclear bone marrow cells (BMC) has an anticonvulsant effect in acute epilepsy. Here, we used pilocarpine to induce epilepsy in rats and studied the effects of BMC injected intravenously either at the onset of seizures or after 10 months of recurrent seizures. BMC effectively decreased seizure frequency and duration. In addition, decreased levels of proinflammatory cytokines (TNF-α, IL-1ß and IL-6) and increased levels of anti-inflammatory cytokine (IL-10) were observed in the brain and serum of BMC-treated rats. Transplants performed at seizure-onset protected against pilocarpine-induced neuronal loss and gliosis and stimulated the proliferation of new neurons in epileptic rats. Our data demonstrate that BMC transplantation has potent therapeutic effects and could be a potential therapy for clinically intractable epilepsies.
Subject(s)
Bone Marrow Transplantation , Cytokines/biosynthesis , Epilepsy/metabolism , Epilepsy/surgery , Leukocytes, Mononuclear/transplantation , Neurons/metabolism , Animals , Bone Marrow Transplantation/methods , Bone Marrow Transplantation/pathology , Cell Movement/physiology , Epilepsy/pathology , Incidence , Inflammation Mediators/metabolism , Leukocytes, Mononuclear/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neurons/pathology , Rats , Rats, WistarABSTRACT
In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.