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Background Sleep disorders (SDs) are a symptom of the prodromal phase of neurodegenerative disorders that are mechanistically linked to the protein α-synuclein (α-syn) including Parkinson’s disease (PD). SDs during the prodromal phase could result from neurodegeneration induced in state-controlling neurons by accumulation of α-syn predominant early in the disease, and consistent with this, we reported the monomeric form of α-syn (monomeric α-syn; α-synM) caused cell death in the laterodorsal tegmental nucleus (LDT), which controls arousal as well as the sleep and wakefulness state. However, we only examined the male LDT, and since sex is considered a risk factor for the development of α-syn-related diseases including prodromal SDs, the possibility exists of sex-based differences in α-synM effects. Accordingly, we examined the hypothesis that α-synM exerts differential effects on membrane excitability, intracellular calcium, and cell viability in the LDT of females compared to males. Methods Patch clamp electrophysiology, bulk load calcium imaging, and cell death histochemistry were used in LDT brain slices to monitor responses to α-synM and effects of GABA receptor acting agents. Results Consistent with our hypothesis, we found opposite effects of α-synM on female LDT neurons when compared to male. In the females, α-synM induced a decrease in membrane excitability and reductions in intracellular calcium which were reliant on functional GABAergic receptors, as well as decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) with a concurrent reduction in action potential firing rate. Cell viability studies showed higher α-syn-mediated neurodegeneration in males compared to females, that depended on inhibitory amino acid transmission. Further, GABA receptor agonists reduced cell death in males. Conclusions When taken together, we conclude that α-synM induces a sex-dependent effect on LDT neurons involving a GABA receptor-mediated mechanism which is neuroprotective. Understanding the potential sex differences in neurodegenerative processes, especially those occurring early in the disease, could enable implementation of sex-based strategies to identify prodromal PD cases, and promote efforts to illuminate new directions for tailored treatment and management of PD.

The idiopathic focal epilepsies members Landau-Kleffner syndrome a. Historically:The original work made it for Landau and Kleffner and published in 1957 reports the cases of five children with epilepsy and acquired aphasia. The clinical findings of these patients were generalized, partial, myoclonic, or absence seizures, all developed aphasia for different periods of time. In the EEG was evident a paroxysmal disorder, usually bilateral, often more predominant in temporal localization with generalized spikes. 3 After that in 1992, Paquiet et al, publish the first review of the literature about it. 4 In 1999 Rossi et al. 5 and in 2003 Mukhinet al describe the EEG findings and progression in patients with LKS. 6 In 2001 Robinson et al, demonstrated that children with ESES have no presence of clinical alteration in language capacities in relation with LKS 7 and in 2004 McVicar and Shinnar confirmed that clinically the syndrome present a limitation in the language