Longone P.,Molecular Neurobiology Unit |
di Michele F.,Experimental Neurology |
D'Agati E.,University of Rome Tor Vergata |
Romeo E.,University of Rome Tor Vergata |
And 2 more authors.
Frontiers in Endocrinology | Year: 2011
Anxiety disorders are the most common psychiatric disorders. They are frequently treated with benzodiazepines, which are fast acting highly effective anxiolytic agents. However, their long-term use is impaired by tolerance development and abuse liability. In contrast, antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are considered as first-line treatment but have a slow onset of action. Neurosteroids are powerful allosteric modulators of GABAA and glutamate receptors. However, they also modulate sigma recep-tors and they are modulated themselves by SSRIs. Both pre-clinical and clinical studies have shown that neurosteroid homeostasis is altered in depression and anxiety disorders and antidepressants may act in part through restoring neurosteroid disbalance. Moreover, novel drugs interfering with neurosteroidogenesis such as ligands of the translocator pro-tein (18 kDa) may represent an attractive pharmacological option for novel anxiolytics which lack the unwarranted side effects of benzodiazepines. Thus, neurosteroids are important endogenous neuromodulators for the physiology and pathophysiology of anxiety and they may constitute a novel therapeutic approach in the treatment of these disorders. © 2011 Longone, di Michele, D'Agati, Romeo, Pasini and Rupprecht.
Temporal lobe epilepsy with mesial temporal sclerosis: Hippocampal neuronal loss as a predictor of surgical outcome [Epilepsia do lobo temporal com esclerose mesial temporal: O padrão da perda neuronal hipocampal como preditor do prognóstico cirúrgico]
Jardim A.P.,Federal University of Sao Paulo |
Neves R.S.C.,Federal University of Sao Paulo |
Caboclo L.O.S.F.,Federal University of Sao Paulo |
Lancellotti C.L.P.,Santa Casa de Sao Paulo |
And 5 more authors.
Arquivos de Neuro-Psiquiatria | Year: 2012
Objective: To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. Method: Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. Results: Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). Conclusion: Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS. Key words epilepsy, temporal lobe, mesial temporal sclerosis, hippocampal sclerosis, pathology, surgical prognosis with TLE-MTS.
Di Michele F.,Experimental Neurology |
Luchetti S.,Royal Netherlands Academy of Arts and science |
Bernardi G.,Experimental Neurology |
Bernardi G.,University of Rome Tor Vergata |
And 2 more authors.
Frontiers in Neuroendocrinology | Year: 2013
Parkinson's disease (PD) is associated with a massive loss of dopaminergic cells in the substantia nigra leading to dopamine hypofunction and alteration of the basal ganglia circuitry. These neurons, are under the control, among others, of the excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA) systems. An imbalance between these systems may contribute to excitotoxicity and dopaminergic cell death. Neurosteroids, a group of steroid hormones synthesized in the brain, modulate the function of several neurotransmitter systems. The substantia nigra of the human brain expresses high concentrations of allopregnanolone (3α, 5αtetrahydroprogesterone), a neurosteroid that positively modulates the action of GABA at GABAA receptors and of 5α-dihydroprogesterone, a neurosteroid acting at the genomic level. This article reviews the roles of NS acting as neuroprotectants and as GABAA receptor agonists in the physiology and pathophysiology of the basal ganglia, their impact on dopaminergic cell activity and survival, and potential therapeutic application in PD. © 2013 Elsevier Inc.
Goto E.M.,Federal University of Sao Paulo |
Silva M.d.P.,Nove de Julho University |
Perosa S.R.,Experimental Neurology |
Arganaraz G.A.,Experimental Neurology |
And 5 more authors.
Neuropeptides | Year: 2010
The aim of this study was to analyze the expression of survival-related molecules such Akt and integrin-linked kinase (ILK) to evaluate Akt pathway activation in epileptogenesis process. Furthermore, was also investigated the mRNA expression of neuropeptide Y, a considered antiepileptic neuropeptide, in the pilocarpine-induced epilepsy. Male Wistar rats were submitted to the pilocarpine model of epilepsy. Hippocampi were removed 6 h (acute phase), 12 h (late acute), 5d (silent) and 60d (chronic) after status epilepticus (SE) onset, and from animals that received pilocarpine but did not develop SE (partial group). Hippocampi collected were used to specify mRNA expression using Real-Time PCR. Immunohistochemistry assay was employed to place ILK distribution in the hippocampus and Western blot technique was used to determine Akt activation level. A decrease in ILK mRNA content was found during acute (0.39 ± 0.03) and chronic (0.48 ± 0.06) periods when compared to control group (0.87 ± 0.10). Protein levels of ILK were also diminished during both periods. Partial group showed increased ILK mRNA expression (0.80 ± 0.06) when compared with animals in the acute stage. Silent group had ILK mRNA and immunoreactivity similar to control group. Western blot assay showed an augmentation in Akt activation in silent period (0.52 ± 0.03) in comparison with control group (0.44 ± 0.01). Neuropeptide Y mRNA expression increased in the partial group (1.67 ± 0.22) and in the silent phase (1.45 ± 0.29) when compared to control group (0.36 ± 0.12). Results suggest that neuropeptide Y (as anticonvulsant) might act in protective mechanisms occurred during epileptic phenomena. Together with ILK expression and Akt activation, these molecules could be involved in hippocampal neuroprotection in epilepsy. © 2009 Elsevier Ltd. All rights reserved.