Hidden prenatal malnutrition in the rat: role of β1-adrenoceptors on synaptic plasticity in the frontal cortex

Objective: To investigate the role of TLR4 on the microglia activation in the pre-frontal cortex, which leads to autism-like behavior of the offspring induced by maternal lipopolysaccharide (LPS) exposure.Methods: Pregnant TLR4−/− (knockout, KO) and WT (wild type, WT) dams were intraperitoneally injected with LPS or PBS, respectively. The levels of TNFα, IL-1β, and IL-6 in the maternal serum and fetal brain were assessed with ELISA following LPS exposure. The gestation period, litter size and weight of the offspring were evaluated. Three-chamber sociability test, open field test and olfactory habituation/dishabituation test were used to assess the offspring's autism-like behavior at 7 weeks of age. Western blotting was performed to examine the levels of TLR4, Phospho-NFκB p65, IKKα, IBA-1, iNOS, Arg-1, C3, CR3A, NMDAR2A, and Syn-1 expression in the pre-frontal cortex. The morphological changes in the microglia, the distribution and expression of TLR4 were observed by immunofluorescence staining. Golgi-Cox staining was conducted to evaluate the dendritic length and spine density of the neurons in 2-week-old offspring.Results: Maternal LPS stimulation increased serum TNFα and IL-6, as well as fetal brain TNFα in the WT mice. The litter size and the weight of the WT offspring were significantly reduced following maternal LPS treatment. LPS-treated WT offspring had lower social and self-exploration behavior, and greater anxiety and repetitive behaviors. The protein expression levels of TLR4 signaling pathways, including TLR4, Phospho-NFκB p65, IKKα, and IBA-1, iNOS expression were increased in the LPS-treated WT offspring, whereas Arg-1 was decreased. Maternal LPS treatment resulted in the significant reduction in the levels of the synaptic pruning-related proteins, C3 and CR3A. Moreover, the neuronal dendritic length and spine density, as well as the expression levels of the synaptic plasticity-related proteins, NMDAR2A and Syn-1 were reduced in the WT offspring; however, gestational LPS exposure had no effect on the TLR4−/− offspring.Conclusion: Activation of TLR4 signaling pathway following maternal LPS exposure induced the abnormal activation of microglia, which in turn was involved in excessive synaptic pruning to decrease synaptic plasticity in the offspring. This may be one of the reasons for the autism-like behavior in the offspring mice.

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Faculty Opinions recommendation of Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1019172.253673 ◽

2004 ◽

Author(s):

Michael Ehlers

Keyword(s):

Synaptic Plasticity ◽

Nmda Receptor ◽

Receptor Subtypes ◽

Hippocampal Synaptic Plasticity

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Role of Nicotinic and Muscarinic Receptors on Synaptic Plasticity and Neurological Diseases

Current Pharmaceutical Design ◽

10.2174/1381612822666160127112021 ◽

2016 ◽

Vol 22 (14) ◽

pp. 2004-2014 ◽

Cited By ~ 13

Author(s):

Marco Fuenzalida ◽

Miguel Ángel Pérez ◽

Hugo R. Arias

Keyword(s):

Synaptic Plasticity ◽

Muscarinic Receptors ◽

Neurological Diseases

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Dysregulation of Astrocyte–Neuronal Communication in Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22157887 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7887

Author(s):

Carmen Nanclares ◽

Andres Mateo Baraibar ◽

Alfonso Araque ◽

Paulo Kofuji

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Synaptic Plasticity ◽

Neuronal Excitability ◽

Active Role ◽

Ionic Homeostasis ◽

Neuronal Communication ◽

Structural Support

Recent studies implicate astrocytes in Alzheimer’s disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters. Here, we review how this “active” role of astrocytes at synapses could contribute to synaptic and neuronal network dysfunction and cognitive impairment in AD.

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Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood–Brain Interface

Biomolecules ◽

10.3390/biom11030359 ◽

2021 ◽

Vol 11 (3) ◽

pp. 359

Author(s):

Maximilian Lenz ◽

Amelie Eichler ◽

Andreas Vlachos

Keyword(s):

Synaptic Plasticity ◽

Brain Stimulation ◽

Vascular Function ◽

Neuropsychiatric Symptoms ◽

Systemic Infection ◽

Brain Functions ◽

Blood Brain ◽

Brain Interface ◽

The Central Nervous System

Inflammation of the central nervous system can be triggered by endogenous and exogenous stimuli such as local or systemic infection, trauma, and stroke. In addition to neurodegeneration and cell death, alterations in physiological brain functions are often associated with neuroinflammation. Robust experimental evidence has demonstrated that inflammatory cytokines affect the ability of neurons to express plasticity. It has been well-established that inflammation-associated alterations in synaptic plasticity contribute to the development of neuropsychiatric symptoms. Nevertheless, diagnostic approaches and interventional strategies to restore inflammatory deficits in synaptic plasticity are limited. Here, we review recent findings on inflammation-associated alterations in synaptic plasticity and the potential role of the blood–brain interface, i.e., the blood–brain barrier, in modulating synaptic plasticity. Based on recent findings indicating that brain stimulation promotes plasticity and modulates vascular function, we argue that clinically employed non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, could be used for monitoring and modulating inflammation-induced alterations in synaptic plasticity.

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The role of elevated autophagy on the synaptic plasticity impairment caused by CdSe/ZnS quantum dots

Biomaterials ◽

10.1016/j.biomaterials.2013.09.048 ◽

2013 ◽

Vol 34 (38) ◽

pp. 10172-10181 ◽

Cited By ~ 41

Author(s):

Liang Chen ◽

Yanyan Miao ◽

Lin Chen ◽

Peipei Jin ◽

Yingying Zha ◽

...

Keyword(s):

Quantum Dots ◽

Synaptic Plasticity

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Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20143407 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3407 ◽

Cited By ~ 2

Author(s):

Paola Imbriani ◽

Annalisa Tassone ◽

Maria Meringolo ◽

Giulia Ponterio ◽

Graziella Madeo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Synaptic Plasticity ◽

Mouse Model ◽

Caspase 3 ◽

Cysteine Proteases ◽

Synaptic Function ◽

Adult Brain ◽

Striatal Slices

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.

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