Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders.

Social behavior is essential for the well-being and survival of individuals. However, social isolation is a serious public health issue, especially during the COVID-19 pandemic, affecting a significant number of people worldwide, and can lead to serious psychological crises. Microglia, innate immune cells in the brain, are strongly implicated in the development of psychiatry. Although many microglial inhibitors have been used to treat depression, there is no literature report on pexidartinib (PLX3397) and social isolation. Herein, we adopted PLX3397 to investigate the role of microglia in the modulation of social isolation. Our results found that social isolation during adolescence caused depressive-like, but not anxiety-like behavior in mice in adulthood, with enhanced expression of the microglial marker Iba1 in the hippocampus. In addition, treatment with PLX3397 reduced the expression of the microglial marker Iba1, decreased the mRNA expression of IL-1ß, increased the mRNA expression of Arg1, elevated the protein levels of DCX and GluR1 and restored the dendritic spine branches and density, ultimately mitigating depressive-like behavior in mice. These findings suggest that inhibition of microglia in the hippocampus could ameliorate mood disorders in mice, providing a new perspective for the treatment of psychiatric disorders such as depression.

MicroRNA-Mediated Silencing Pathways in the Nervous System and Neurological Diseases.

MicroRNAs (miRNAs) are small noncoding RNAs that play a prominent role in post-transcriptional gene regulation mechanisms in the brain tuning synaptic plasticity, memory formation, and cognitive functions in physiological and pathological conditions [...].

Speech-language pathology approaches to neurorehabilitation in acute care during COVID-19: Capitalizing on neuroplasticity.

Neurologic manifestations associated with a coronavirus disease 2019 (COVID-19) diagnosis are common and often occur in severe and critically ill patients. In these patients, the neurologic symptoms are confounded by critical care conditions, such as acute respiratory distress syndrome (ARDS). Patients with dual diagnoses of COVID-19 and neurologic changes such as myopathy, polyneuropathy, and stroke are likely at a higher risk of experiencing deficits with swallowing, communication, and/or cognition. Speech-language pathologists are an integral part of both the critical care and neurologic disorders multi-disciplinary teams, offering valuable contributions in the evaluation, treatment, and management of these areas. Patients in intensive care units (ICUs) who require mechanical ventilation often experience difficulty with communication and benefit from early speech-language pathology intervention to identify the most efficient communication methods with the medical team and caregivers. Moreover, patients with neurologic manifestations may present with cognitive-linguistic impairments such as aphasia, thereby increasing the need for communication-based interventions. Difficulties with voice and swallowing after extubation are common, often requiring frequent treatment sessions, possibly persisting beyond ICU discharge. After leaving the ICU, patients with COVID-19 often experience physical, cognitive, and mental health impairments collectively called post-intensive care syndrome. This is often a lengthy road as they progress toward full recovery, requiring continued speech-language pathology treatment after hospital discharge, capitalizing on the principles of neuroplasticity.

Neurobehavioral, neurochemical and synaptic plasticity perturbations during postnatal life of rats exposed to chloroquine in-utero.

Despite reports that quinoline antimalarials including chloroquine (Chq) exhibit idiosyncratic neuropsychiatric effects even at low doses, the drug continues to be in widespread use during pregnancy. Surprisingly, very few studies have examined the potential neurotoxic action of Chq exposure at different points of gestation or how this phenomenon may affect neurophysiological well-being in later life. We therefore studied behavior, and the expression of specific genes and neurochemicals modulating crucial neural processes in offspring of rats exposed to prophylactic dose of Chq during different stages of gestation. Pregnant rats were injected 5 mg/kg/day (3 times) of Chq either during early- (first week), mid- (second week), late- (third week), or throughout- (all weeks) gestation, while controls received PBS injection. Behavioral characterization of offspring between postnatal days 15-20 in the open field, Y-maze, elevated plus and elevated zero mazes revealed that Chq evoked anxiogenic responses and perturbed spatial memory in rats, although locomotor activity was generally unaltered. In the prefrontal cortex (PFC), hippocampus and cerebellum of rats prenatally exposed to Chq, RT-qPCR analysis revealed decreased mRNA expression of presynaptic marker synaptophysin, which was accompanied by downregulation of postsynaptic marker PSD95. Synaptic marker PICK1 expression was also downregulated in the hippocampus but was unperturbed in the PFC and cerebellum. In addition to recorded SOD downregulation in cortical and hippocampal lysates, induction of oxidative stress in rats prenatally exposed to Chq was corroborated by lipid peroxidation as evinced by increased MDA levels. Offspring of rats infused with Chq at mid-gestation and weekly treatment throughout gestation were particularly susceptible to neurotoxic changes, especially in the hippocampus. Interestingly, Chq did not cause histopathological changes in any of the brain areas. Taken together, our findings causally link intrauterine exposure to Chq with postnatal behavioral impairment and neurotoxic changes in rats.

Facemasks and face recognition: Potential impact on synaptic plasticity.

Visual recognition of facial expression modulates our social interactions. Compelling experimental evidence indicates that face conveys plenty of information that are fundamental for humans to interact. These are encoded at neural level in specific cortical and subcortical brain regions through activity- and experience-dependent synaptic plasticity processes. The current pandemic, due to the spread of SARS-CoV-2 infection, is causing relevant social and psychological detrimental effects. The institutional recommendations on physical distancing, namely social distancing and wearing of facemasks are effective in reducing the rate of viral spread. However, by impacting social interaction, facemasks might impair the neural responses to recognition of facial cues that are overall critical to our behaviors. In this survey, we briefly review the current knowledge on the neurobiological substrate of facial recognition and discuss how the lack of salient stimuli might impact the ability to retain and consolidate learning and memory phenomena underlying face recognition. Such an "abnormal" visual experience raises the intriguing possibility of a "reset" mechanism, a renewed ability of adult brain to undergo synaptic plasticity adaptations.

Neuroinflammation and Brain Development: Possible Risk Factors in COVID-19-Infected Children.

COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus, affects children in a different way than it does in adults, with milder symptoms. However, several cases of neurological symptoms with neuroinflammatory syndromes, such as the multisystem inflammatory syndrome (MIS-C), following mild cases, have been reported. As with other viral infections, such as rubella, influenza, and cytomegalovirus, SARS-CoV-2 induces a surge of proinflammatory cytokines that affect microglial function, which can be harmful to brain development. Along with the viral induction of neuroinflammation, other noninfectious conditions may interact to produce additional inflammation, such as the nutritional imbalance of fatty acids and polyunsaturated fatty acids and alcohol consumption during pregnancy. Additionally, transient thyrotoxicosis induced by SARS-CoV-2 with secondary autoimmune hypothyroidism has been reported, which could go undetected during pregnancy. Together, those factors may pose additional risk factors for SARS-CoV-2 infection impacting mechanisms of neural development such as synaptic pruning and neural circuitry formation. The present review discusses those conditions in the perspective of the understanding of risk factors that should be considered and the possible emergence of neurodevelopmental disorders in COVID-19-infected children.