Postnatal fluoxetine treatment alters perineuronal net formation and maintenance in the hippocampus

Mukhopadhyay, Sourish; Chatterjee, Ashmita; Tiwari, Praachi; Ghai, Utkarsha; Vaidya, Vidita A.

doi:10.1101/2020.10.12.336941

Cited by 3 publications

(1 citation statement)

References 89 publications

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“…In two separate studies (Ohira et al, 2013;Guirado et al, 2014), FLX treated mice showed decreased PNN density and PV+ neurons in both mPFC and in hippocampus compared to vehicle. In concurrence with these findings, Mukhopadhyay et al, 2021 found a decrease in CA1 and CA3 hippocampal PNNs following FLX treatment in Sprague Dawley rats (Mukhopadhyay et al, 2021). Moreover, Ohira et al, 2019 found reduction of DG and CA3 hippocampal PNN density and PV+ interneurons in FLX treated marmosets (Ohira et al, 2019).…”

Section: Therapeutic Manipulation Of Pnnsmentioning

confidence: 77%

Matrix disequilibrium in Alzheimer’s disease and conditions that increase Alzheimer’s disease risk

et al. 2023

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Alzheimer’s Disease (AD) and related dementias are a leading cause of death globally and are predicted to increase in prevalence. Despite this expected increase in the prevalence of AD, we have yet to elucidate the causality of the neurodegeneration observed in AD and we lack effective therapeutics to combat the progressive neuronal loss. Throughout the past 30 years, several non-mutually exclusive hypotheses have arisen to explain the causative pathologies in AD: amyloid cascade, hyper-phosphorylated tau accumulation, cholinergic loss, chronic neuroinflammation, oxidative stress, and mitochondrial and cerebrovascular dysfunction. Published studies in this field have also focused on changes in neuronal extracellular matrix (ECM), which is critical to synaptic formation, function, and stability. Two of the greatest non-modifiable risk factors for development of AD (aside from autosomal dominant familial AD gene mutations) are aging and APOE status, and two of the greatest modifiable risk factors for AD and related dementias are untreated major depressive disorder (MDD) and obesity. Indeed, the risk of developing AD doubles for every 5 years after ≥ 65, and the APOE4 allele increases AD risk with the greatest risk in homozygous APOE4 carriers. In this review, we will describe mechanisms by which excess ECM accumulation may contribute to AD pathology and discuss pathological ECM alterations that occur in AD as well as conditions that increase the AD risk. We will discuss the relationship of AD risk factors to chronic central nervous system and peripheral inflammation and detail ECM changes that may follow. In addition, we will discuss recent data our lab has obtained on ECM components and effectors in APOE4/4 and APOE3/3 expressing murine brain lysates, as well as human cerebrospinal fluid (CSF) samples from APOE3 and APOE4 expressing AD individuals. We will describe the principal molecules that function in ECM turnover as well as abnormalities in these molecular systems that have been observed in AD. Finally, we will communicate therapeutic interventions that have the potential to modulate ECM deposition and turnover in vivo.

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Section: Therapeutic Manipulation Of Pnnsmentioning

confidence: 77%

Matrix disequilibrium in Alzheimer’s disease and conditions that increase Alzheimer’s disease risk

et al. 2023

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Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats

et al. 2023

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Acupuncture help alleviate depression-like behaviors, but the neural mechanisms behind such antidepressive impacts are still unknown. Abnormalities in the perineuronal net (PNN) have been documented in multiple psychiatric disorders. The modulation and neural mechanism of PNNs in the antidepressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points were investigated in this work. A rat depression model was induced by chronic unpredicted mild stress (CUMS). Acupuncture was performed on model rats in the EA group at GV20 and GV29 acupoints every other day for 30 min each time. The uoxetine (FLX) group of model rats were gavaged with 10 mg/kg uoxetine each day. Immunohistochemistry and western blot assays were used to evaluate the density and components of PNNs, the protein expression levels of the main synthase of GABA, GAD67, and of the synaptic proteins GLuA1, and PSD95 in the pre-limbic (PrL) and sub-limbic (IL) of mPFC. We found that four weeks of CUMS could decrease the levels of PNN component proteins aggrecan and brevican and GAD67.Electroacupuncture exhibited signi cant anti-depressive effects on depressive rats by altering the levels of PNNs. Speci cally, aggrecan and brevican are involved in the anti-depression mechanism of electroacupuncture. After electroacupuncture treatment, the decreased expression of GAD67, GLuA1 and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. This indicates that the mechanism of acupuncture's antidepressant effect may be based on reversing the stress-induced decline in PNN expression, the functional impairment of GABA neurons, and the regulation of excitatory synaptic expression.

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Neural Extracellular Matrix Remodeling Signatures in Genetic and Acquired Mouse Models of Epilepsy

Blondiaux

Jia

Annamneedi

et al. 2023

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Epilepsies are multifaceted neurological disorders characterized by abnormal brain activity, e.g. caused by imbalanced synaptic excitation and inhibition. The neural extracellular matrix (ECM) is dynamically modulated by physiological and pathophysiological activity and critically involved in controlling the brain's excitability. We used different epilepsy models, i.e. mice lacking the presynaptic scaffolding protein Bassoon at excitatory, inhibitory or all synapse types as genetic models for rapidly generalizing early-onset epilepsy, and intra-hippocampal kainate injection, a model for acquired temporal lobe epilepsy, to study the relationship between epileptic seizures and ECM composition. Electroencephalogram recordings revealed Bassoon deletion at excitatory or inhibitory synapses having diverse effects on epilepsy-related phenotypes. While constitutive Bsn mutants and GABAergic neuron-specific knockouts(BsnDlx5/6cKO) displayed severe epilepsy with more and stronger seizures than kainate-injected animals, mutants lacking Bassoon solely in excitatory forebrain neurons (BsnEmx1cKO) showed only mild impairments. By semiquantitative immunoblotting and immunohistochemistry we show model-specific patterns of neural ECM remodeling, and we also demonstrate significant upregulation of the ECM receptor CD44 in null and BsnDlx5/6cKO mutants. ECM-associated WFA-binding chondroitin sulfates were strongly augmented in seizure models. Strikingly, Brevican, Neurocan, Aggrecan and link protein Hapln1 levels reliably predicted seizure properties across models, suggesting a link between ECM state and epileptic phenotype.

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Postnatal fluoxetine treatment alters perineuronal net formation and maintenance in the hippocampus

Cited by 3 publications

References 89 publications

Matrix disequilibrium in Alzheimer’s disease and conditions that increase Alzheimer’s disease risk

Matrix disequilibrium in Alzheimer’s disease and conditions that increase Alzheimer’s disease risk

Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats

Neural Extracellular Matrix Remodeling Signatures in Genetic and Acquired Mouse Models of Epilepsy

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