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1.
Dis Model Mech ; 16(7)2023 07 01.
Article in English | MEDLINE | ID: mdl-37458166

ABSTRACT

An outbreak of births of microcephalic patients in Brazil motivated multiple studies on this incident. The data left no doubt that infection by Zika virus (ZIKV) was the cause, and that this virus promotes reduction in neuron numbers and neuronal death. Analysis of patients' characteristics revealed additional aspects of the pathology alongside the decrease in neuronal number. Here, we review the data from human, molecular, cell and animal model studies attempting to build the natural history of ZIKV in the embryonic central nervous system (CNS). We discuss how identifying the timing of infection and the pathways through which ZIKV may infect and spread through the CNS can help explain the diversity of phenotypes found in congenital ZIKV syndrome (CZVS). We suggest that intraneuronal viral transport is the primary mechanism of ZIKV spread in the embryonic brain and is responsible for most cases of CZVS. According to this hypothesis, the viral transport through the blood-brain barrier and cerebrospinal fluid is responsible for more severe pathologies in which ZIKV-induced malformations occur along the entire anteroposterior CNS axis.


Subject(s)
Microcephaly , Zika Virus Infection , Zika Virus , Animals , Humans , Zika Virus Infection/complications , Microcephaly/etiology , Microcephaly/pathology , Central Nervous System/pathology , Blood-Brain Barrier/pathology , Brain/pathology
2.
Exp Neurol ; 326: 113175, 2020 04.
Article in English | MEDLINE | ID: mdl-31923390

ABSTRACT

Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4-5- month-old) and old (11-13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1h after salicylate (300mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4-6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.


Subject(s)
Aging/psychology , Anxiety/chemically induced , Anxiety/psychology , Hallucinogens/therapeutic use , Methoxydimethyltryptamines/therapeutic use , Salicylates , Animals , Anxiety/prevention & control , Behavior, Animal , Electroencephalography/drug effects , Evoked Potentials, Auditory, Brain Stem , Hearing Loss, Noise-Induced/complications , Hippocampus/physiopathology , Male , Mice , Mice, Inbred C57BL , Microelectrodes , Motor Activity , Prefrontal Cortex/physiopathology , Salicylates/antagonists & inhibitors , Tinnitus/chemically induced , Tinnitus/physiopathology , Tinnitus/psychology
3.
Brain Sci ; 9(2)2019 Jan 23.
Article in English | MEDLINE | ID: mdl-30678038

ABSTRACT

Microelectrode implants are an important tool in neuroscience research and in developing brain⁻machine interfaces. Data from rodents have consistently shown that astrocytes are recruited to the area surrounding implants, forming a glial scar that increases electrode impedance and reduces chronic utility. However, studies in non-human primates are scarce, with none to date in marmosets. We used glial fibrillary acidic protein (GFAP) immunostaining to characterize the acute and chronic response of the marmoset brain to microelectrodes. By using densitometry, we showed that marmoset astrocytes surround brain implants and that a glial scar is formed over time, with significant increase in the chronic condition relative to the acute condition animal.

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