Viral infection during early stage of life influences brain development and results in several neurodevelopmental disorders such as schizophrenia, autism and behavioral abnormalities. However, the mechanism through which infection causes long-term behavioral defects is not well known. To elucidate this, we have used synthetic polyinosinic-polycytidylic acid [poly (I:C)] which acts as a dsRNA molecule and interacts with toll-like receptor-3 (TLR-3) of microglia cells to evoke the immune system, thus mimicking the viral infection. Rat pups of postnatal day (PND) 7 were infused with a single dose of poly (I:C) (5 mg/kg BW) and vehicle alone to controls. When these pups grew to 3, 6 and 12 weeks, their spatial and fear conditioning memory were impaired as assessed by Morris water maze and passive avoidance test, respectively. We checked the immune activation by staining of TNF-α in the hippocampus and observed that poly (I:C) exposure elevated the number of TNF-α positive cells immediately after 12 h of infusion in one week rat and it persisted up to postnatal age of 3 and 12 weeks. Moreover, poly (I:C) significantly decreased the binding of H-QNB to the cholinergic receptors in the frontal cortex and hippocampus of 3 and 6 weeks rats as compared to control but did not change significantly in 12 weeks rats. RT-PCR and immunoblotting results showed that poly (I:C) exposure upregulated the expression of memory associated genes (BDNF, Arc, EGR1) at mRNA and protein level in frontal cortex and hippocampus of 3 weeks rats as compared to control. However, long-time persistence of poly (I:C) effects significantly decreased the expression of these genes in both brain regions of 12 weeks rats. Taken together, it is evident that early life exposure to poly (I:C) has a long-term effect and impairs learning and memory, probably through TNF-α mediated neuroinflammation and alteration in the expression of memory associated genes in frontal cortex and hippocampus of rats.
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http://dx.doi.org/10.1016/j.nlm.2018.09.005 | DOI Listing |
Sci Adv
January 2025
Laboratory for Biofunction Dynamics Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Placebo analgesia is caused by inactive treatment, implicating endogenous brain function involvement. However, the neurobiological basis remains unclear. In this study, we found that μ-opioid signals in the medial prefrontal cortex (mPFC) activate the descending pain inhibitory system to initiate placebo analgesia in neuropathic pain rats.
View Article and Find Full Text PDFSci Robot
January 2025
Sony Computer Science Laboratories Inc. (Sony CSL), Tokyo, Japan.
For trained individuals such as athletes and musicians, learning often plateaus after extensive training, known as the "ceiling effect." One bottleneck to overcome it is having no prior physical experience with the skill to be learned. Here, we challenge this issue by exposing expert pianists to fast and complex finger movements that cannot be performed voluntarily, using a hand exoskeleton robot that can move individual fingers quickly and independently.
View Article and Find Full Text PDFInflamm Bowel Dis
January 2025
Department of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
Background: Extraintestinal symptoms (EIS) in inflammatory bowel diseases, including fatigue, depression and anxiety, are highly prevalent, but poorly understood. Alterations of brain function may contribute to EIS, but their association with disease activity is unclear. This study analyzed intrinsic neural activity (INA) of individuals with Crohn's disease (CD) in different disease states and examined the relationship between INA and EIS.
View Article and Find Full Text PDFFront Neurol
December 2024
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Introduction: Neonatal seizures are the most common clinical manifestation of neurological dysfunction in newborns, with an incidence ranging from 1 to 5‰. However, the therapeutic efficacy of current pharmacological treatments remains suboptimal. This study aims to utilize genetically modified hamsters with hypertriglyceridaemia (HTG) to investigate the effects of elevated triglycerides on neuronal excitability and to elucidate the underlying mechanisms.
View Article and Find Full Text PDFEur J Neurosci
January 2025
Department of Kinesiology, Trent University, Peterborough, ON, Canada.
Previous research on resting muscles has shown that inter-pulse interval (IPI) duration influences transcranial magnetic stimulation (TMS) responses, which can introduce serious confounding variables into investigations if not accounted for. However, it is far less clear how IPI influences TMS responses in active muscles. Thus, the purpose of this study was to examine the relationship between IPI and corticospinal excitability during submaximal isometric elbow flexion.
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