Although congenital Zika virus (ZIKV) exposure has been associated with microcephaly and other neurodevelopmental disorders, long-term consequences of perinatal infection are largely unknown. We evaluated short- and long-term neuropathological and behavioral consequences of neonatal ZIKV infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. During the acute phase of infection, mice developed frequent seizures, which were reduced by tumor necrosis factor-α (TNF-α) inhibition. During adulthood, ZIKV replication persisted in neonatally infected mice, and the animals showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications. Altogether, the results show that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-α-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities.
Patients with Parkinson’s disease (PD) manifest nonmotor and motor symptoms. Autonomic cardiovascular dysregulation is a common nonmotor manifestation associated with increased morbimortality. Conventional clinical treatment alleviates motor signs but does not change disease progression and fails in handling nonmotor features. Nutrition is a key modifiable determinant of chronic disease. This study aimed to assess the effects of propolis on cardiological features, heart rate (HR) and heart rate variability (HRV) and on nigrostriatal dopaminergic damage, detected by tyrosine hydroxylase (TH) immunoreactivity, in the 6-hydroxydopamine (6-OHDA) rat model of PD. Male Wistar rats were injected bilaterally with 6-OHDA or saline into the striatum and were treated with propolis or water for 40 days. Autonomic function was assessed by time domain parameters (standard deviation of all normal-to-normal intervals (SDNN) and square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD)) of HRV calculated from electrocardiogram recordings. Reductions in HR (p = 1.47 × 10−19), SDNN (p = 3.42 × 10−10) and RMSSD (p = 8.2 × 10−6) detected in parkinsonian rats were reverted by propolis. Propolis attenuated neuronal loss in the substantia nigra (p = 5.66 × 10−15) and reduced striatal fiber degeneration (p = 7.4 × 10−5) in 6-OHDA-injured rats, which also showed significant weight gain (p = 1.07 × 10−5) in comparison to 6-OHDA-lesioned counterparts. Propolis confers cardioprotection and neuroprotection in the 6-OHDA rat model of PD.
Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.
Modulation of brain activity is one of the main mechanisms capable of demonstrating the synchronization dynamics of neural oscillations. in epilepsy, modulation is a key concept since seizures essentially result from neural hypersynchronization and hyperexcitability. in this study, we have introduced a time-dependent index based on the Kullback-Leibler divergence to quantify the effects of phase and frequency modulations of neural oscillations in neonatal mice exhibiting epileptiform activity induced by Zika virus (ZiKV) infection. through this index, we demonstrate that fast oscillations (gamma and beta 2) are the more susceptible modulated rhythms in terms of phase, during seizures, whereas slow waves (delta and theta) mainly undergo changes in frequency. the index also allowed detection of specific patterns associated with the interdependent modulation of phase and frequency in neural activity. furthermore, by comparing ZiKV modulations with the general computational model Epileptors, we verify different signatures related to the brain rhythms modulation in phase and frequency. These findings instigate new studies on the effects of ZIKV infection on neuronal networks from electrophysiological activities, and how different mechanisms can trigger epilepsy.Zika virus (ZIKV) is an arbovirus from the Flaviviridae family, which was first reported in 1947 in Uganda 1 . It is mainly transmitted by the Aedes aegypti mosquitoes, but can also be transmitted sexually and by blood transfusion from an infected donor 2,3 . Zika has been considered as an emergent health threat, given its epidemic history, transmission in tropical areas 4 , neurological, congenital diseases 5,6 , as well as given the fact that it is associated with brain abnormalities in newborns Rasmussen et al. 8 ). Recent reports show that epileptic seizures are among the main neurological outcomes of congenital Zika syndrome (CZS) 9-13 ; additionally, reports of the incidence of epileptic seizures in infants exposed to the ZIKV and who had not developed microcephaly 14 , represent new challenges due to changes in the neurodevelopmental stages and even their long-term consequences.Epilepsy is one of the most common neurological disorders worldwide 15 , clinically characterized by the occurrence of at least two unprovoked seizures in less than 24 hours, high unprovoked seizure recurrence risk, or even by the diagnosis of epilepsy syndrome 16 . Despite important advances in the understanding of the involved pathophysiology, multiple mechanisms behind the hyperexcitability and hypersynchronization of neurons during epileptic seizures, still need to be understood better. For instance, the role of neuronal discharge modulation during seizures and their relationship with epileptogenesis is not yet completely elucidated 17 . A physical approach
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