Françoise Lazarini

• PhD
• Research Investigator at Pasteur Network

OBJECTIVE: To characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection. METHODS: We conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak. RESULTS: Eighty-seven...

Whereas recent investigations have revealed viral, inflammatory and vascular factors involved in SARS-CoV-2 lung pathogenesis, the pathophysiology of neurological disorders in COVID-19 remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecul...

Congenital cytomegalovirus (CMV) infection leads to olfactory bulb lesions in the fetus, yet little is known about its impact on olfaction after birth. Here, we have assessed in a prospective study conducted on children in two French hospitals from 2016 to 2019, infection severity and olfactory performance after congenital CMV infection. Children w...

Background: Zika Virus (ZIKV) infection has been associated with Guillain-Barré Syndrome (GBS). Yet, little is known about the consequence of ZIKV infection on olfaction in humans. Methods: Just right before the COVID-19 outbreak, we prospectively investigated the olfactory capacities of 19 patients with ZIKV-associated GBS from the French West Ind...

Growing evidence implicates the bacterial populations in the nose as an important factor for personal and global health. Here, we provide a brief overview of the nasal microbiome and speculate on its potential roles in olfactory processing and neurodegeneration, with a particular focus on Parkinson’s disease (PD).

The current COVID-19 pandemic illustrates the importance of obtaining reliable methods for the rapid detection of SARS-CoV-2. A highly specific and sensitive diagnostic test able to differentiate the SARS-CoV-2 virus from common human coronaviruses is therefore needed. Coronavirus nucleoprotein (N) localizes to the cytoplasm and the nucleolus and i...

Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. Here we examine the functional and structural consequences of SARS-CoV-2 infection in a reconstructed human bronchial epithelium model. SARS-CoV-2 replication causes a transient decrease in epithelial barrier...

The devastating pandemic due to SARS-CoV-2 and the emergence of antigenic variants that jeopardize the efficacy of current vaccines create an urgent need for a comprehensive understanding of the pathophysiology of COVID-19, including the contribution of inflammation to disease. It also warrants for the search of immunomodulatory drugs that could im...

We detail in this Commentary our hypothesis of functional brain dysfunction in patients with long Covid in relation with the impairment of olfactory pathways, and discuss possible implications for the therapeutic management of these patients.

The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and more than 1.2 million human deaths around the globe ¹ , and most of the severe cases of COVID-19 in humans are associated with neurological symptoms such as anosmia and ageusia, and uncontrolled inflammatory immune re...

40 While recent investigations have revealed viral, inflammatory and vascular factors involved in SARS-41 CoV-2 lung pathogenesis, the pathophysiology of neurological disorders in COVID-19 remains poorly 42 understood. Yet, olfactory and taste dysfunction are rather common in COVID-19, especially in pauci-43 symptomatic patients which constitutes t...

Background It is unclear whether olfactory deficits improve after remission in depressed patients. Therefore, we aimed to assess in drug-free patients the olfactory performance of patients with major depressive episodes (MDE) and its change after antidepressant treatment. Methods In the DEP-ARREST-CLIN study, 69 drug-free patients with a current M...

1 2 Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the 3 parameters controlling the severity of COVID-19. We examined the functional and structural 4 consequences of SARS-CoV-2 infection in a reconstituted human bronchial epithelium model. 5 SARS-CoV-2 replication caused a transient decrease in epithelial b...

Background and purpose The frequency of infectious encephalitis and the distribution of causative pathogens in the tropical areas are poorly known and may be influenced by emerging and rare infections. The aim was to characterize a large series of acute infectious encephalitis and myelitis in immunocompetent patients from the Caribbean island of Gu...

Olfaction is the first sensory modality to develop during fetal life in mammals, and plays a key role in the various behaviors of neonates such as feeding and social interaction. Odorant cues (i.e., mother or predator scents) can trigger potentiation or inhibition of ultrasonic vocalizations (USV) emitted by pups following their isolation. Here, we...

Olfaction is the first sensory modality to develop during fetal life in mammals, and plays a key role in the various behaviors of neonates such as feeding and social interaction. Odorant cues (i.e., mother or predator scents) can trigger potentiation or inhibition of ultrasonic vocalizations (USV) emitted by pups following their isolation. Here, we...

In developed countries, cytomegalovirus (CMV)-infected newborns are at high risk of developing sensorineural handicaps, such as hearing loss, requiring extensive follow-up. However early prognostic tools for auditory damage in children are not yet available. In the fetus, CMV infection leads to early olfactory bulb (OB) damage, suggesting that olfa...

Rationale: The receptor protein tyrosine phosphatase PTPRG has been genetically associated with psychiatric disorders and is a ligand for members of the contactin family, which are themselves linked to autism spectrum disorders. Objective: Based on our finding of a phosphatase-null de novo mutation in PTPRG associated with a case of sporadic sch...

The olfactory bulb (OB) is a highly plastic structure that can change organizational networks depending on environmental inputs in adult mammals. Particularly, in rodents, adult neurogenesis underlies plastic changes in the OB circuitry by continuously adding new interneurons to the network. We addressed the question of whether microglia, the immun...

Unlabelled: Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying physiopathological mechanisms remain poorly understood. We hypothesized that one key link between olfactory deficits and MDD lies in hypercortisolemia, a cardinal symptom of MDD. C...

Subventricular zone (SVZ) neurogenesis continuously provides new GABA- and dopamine (DA)-containing interneurons for the olfactory bulb (OB) in most adult mammals. DAergic interneurons are located in the glomerular layer (GL) where they participate in the processing of sensory inputs. To examine whether adult neurogenesis might contribute to regene...

Neurogenesis underlies plastic changes in defined neuronal circuits in the postnatal and adult brain. Here we identify connective tissue growth factor (CTGF) as a critical factor in the mouse olfactory bulb (OB) in determining the efficiency of incorporation of postnatally born inhibitory neurons, thus gating the output of glomeruli, the first rela...

Microglia, the innate immune cells of the brain, engulf and eliminate cellular debris during brain injury and disease. Recent observations have extended their roles to the healthy brain, but the functional impact of activated microglia on neural plasticity has so far been elusive. To explore this issue, we investigated the role of microglia in the...

Neural stem cells (NSCs) persist in defined brain niches, including the subventricular zone (SVZ), throughout adulthood and generate new neurons destined to support specific neurological functions. Whether brain diseases such as multiple sclerosis (MS) are associated with changes in adult NSCs and whether this might contribute to the development an...

Adult-born neurons arrive to the olfactory bulb (OB) and integrate into the existing circuit throughout life. Despite the prevalence of this phenomenon, its functional impact is still poorly understood. Recent studies point to the importance of newly generated neurons to olfactory learning and memory. Adult neurogenesis is regulated by a variety of...

In mammals, new neurons are recruited into restricted brain areas throughout life. Adult-born neurons produced in the subventricular zone of the lateral ventricle migrate rostrally towards the olfactory bulb. Although thousands of neurons reach this central structure every day, the functional impact of their integration into mature circuits remains...

In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing ne...

Irradiation did not alter the morphology of DCX+ cells reaching the OB. Dendrites were counted for DCX+ cells in the GCL, EPL and GL of sham and irradiated mice, 7 months after irradiation. P>0.05 with Student's t-test (n = 25 from 5 random cells analyzed per OB layer and from 5 mice per group). (2.75 MB EPS)

Complete statistical analysis on spontaneous discrimination. (0.08 MB RTF)

Focal SVZ irradiation inhibited the recruitment of new neurons in the OB but not in the hippocampus. New cells were labeled with BrdU 3 days after the final focal irradiation and survival was evaluated 11 days later. The mean number of BrdU+ cells in the GCL of the OB and in the dentate gyrus of the hippocampus was determined for sham and irradiate...

Complete statistical analysis on neurogenesis data. (0.04 MB RTF)

Complete statistical analysis for operant conditioning. (0.11 MB RTF)

Statistical analysis on 2-odor memory test. (0.03 MB RTF)

DefinitionThis characterizes the lowest level of sound that a listener can reliably detect and is sometimes referred to as threshold of audibility. The units are typically reported in dB sound pressure level (SPL).Psychoacoustics

Ongoing neurogenesis maintains neuronal replacement in a few regions of the mammalian adult brain. One of these regions, the subventricular zone, generates olfactory bulb interneuron precursors that must migrate through the rostral migratory stream to reach the olfactory bulb circuit. There, they rapidly initiate dendritic growth and establish dend...

Dendritic cells (DC) have been suspected to play an important role in prion diseases. We evaluated the role of DC in a murine model of Bovine Spongiform Encephalopathy (BSE) by the use of the growth factor Flt3 ligand, which stimulates DC generation, and CpG oligodeoxynucleotides, which induce DC maturation. We observed that pre-treatments or treat...

We describe three rapid procedures for the in vitro investigation of molecular factors influencing the migration of neural precursors derived from embryonic or postnatal neural stem cells. In the first assay, factors influencing chain migration from the anterior subventricular zone of perinatal mice can be analyzed after explantation and embedding...

Chapitre 18 Mention d'édition : Second Edition

The local-circuit inhibitory interneurons containing gamma-aminobutyric acid (GABA) are continuously replaced in the adult olfactory bulb. Here, we describe how the production of new GABAergic interneurons is adapted to experience-induced plasticity. In particular, we discuss how such an adaptation is sensitive to the level of sensory inputs and ho...

Dendritic cells (DC) are suspected to be involved in transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE). We detected the disease-specific, protease-resistant prion protein (PrP(bse)) in splenic DC purified by magnetic cell sorting 45 days after intraperitoneal inoculation of BSE prions in immunocompetent mic...

Oligodendrocyte development is controlled by a number of survival and migratory factors. The present study shows that signaling of CXCR4 receptor by the chemokine CXCL12 regulates survival and migration of neural precursors (NP) as well as oligodendrocyte progenitors (OP). CXCR4 is expressed by E14 striatal NP and OP generated by neurospheres. In C...

Antigen expression of a human endogenous retrovirus family, HERV-W, in normal human brain and multiple sclerosis lesions was studied by immunohistochemistry by three independent groups. The HERV-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis-associated retroviral element (MSRV). A panel of antibo...

Tau2 antibody recognizes a phosphorylation-independent epitope that is pathologically modified as tau protein is phosphorylated to form neurofibrillary tangles of Alzheimer's disease (AD). Similar modification of tau2 epitope can be induced even in the absence phosphorylation of tau, as we first demonstrated in ischemic foci and in glial cytoplasmi...

To clarify the mechanisms leading to the development of Creutzfeldt-Jakob disease in some recipients of pituitary-derived human growth hormone (hGH), we investigated the effects of repeated injections of low prion doses in mice. The injections were performed, as in hGH-treated children, by a peripheral route at short intervals and for an extended p...

The chemotactic factors directing interneuron migration during cerebrocortical development are essentially unknown. Here we identify the CXC chemokine receptor 4 (CXCR4) in interneuron precursors migrating from the basal forebrain to the neocortex and demonstrate that stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for isolated st...

alpha-chemokines, which control the activation and directed migration of leukocytes, participate in the inflammatory processes in host defense response. One of the alpha-chemokines, CXCL12 or stromal cell-derived factor 1 (SDF-1), not only regulates cell growth and migration of hematopoietic stem cells but may also play a central role in brain deve...

A retroviral element (multiple sclerosis-associated retrovirus, MSRV) defining a family of genetically inherited endogenous retroviruses (human endogenous retrovirus type W, HERV-W) has been characterized in cell cultures from patients with multiple sclerosis. Recently, MSRV retroviral particles or the envelope recombinant protein were shown to dis...

Activation of CXCR4 by the CXC chemokine stromal cell-derived factor-1 (SDF-1) requires interaction of the amino-terminal domains of both molecules. We report that proteinases released from either mononucleated blood cells or polymorphonuclear neutrophils degranulated by inflammatory stimuli generate an SDF-1 fragment that is deleted from amino-ter...

Stromal cell-derived factor 1 (SDF-1) is an alpha-chemokine that stimulates migration of haematopoietic progenitor cells and development of the immune system. SDF-1 is also abundantly and selectively expressed in the developing and mature CNS, as we show here. At embryonic day 15, SDF-1 transcripts were detected in the germinal periventricular zone...

The aim of this study was to develop a series of neuropsychological tests that define the cortical and subcortical features of cognitive impairment and the characteristics of memory in demented and mildly cognitively impaired AIDS patients. We attempted to establish a usable method to assess and determine the type and degree of cognitive impairment...

CXCR4 is the Gi protein-linked seven-transmembrane receptor for the alpha chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate ho...

Transmissible non conventional agents are currently called "Prions". This is not a neutral terminology: the attractive Prion hypothesis (the infectious agent being a protein able to replicate in the absence of DNA or RNA) due to Stanley Prusiner is the prevalent one, and has shown to be heuristic, but has not been formally proven and does not easil...

Simple methods for obtention of primary cultures of isolated astrocytes and microglia from adult simian brain have been developed. Characterization of these two glial cell populations were performed by morphological observations and by immunocytochemistry. The astroglial cultures were obtained by an indirect method. After L-leucine methyl-ester tre...

The relationship between dementia and human immunodeficiency virus type 1 (HIV-1) cerebral load is not clearly understood. We used immunohistochemistry and competitive polymerase chain reaction to evaluate the density ofgp 41 immunostained cells and the amount of HIV-1 DNA and RNA in the midfrontal gyrus of 21 HIV-1 infected patients, nine of whom...

Laboratory savety program organization, surveillance and training have to be modified to take into account the hazards of unconventional infectious agents or prions. These are resistant to most decontamination or fixation methods. In France, there are guidelines for human pathology laboratories, but little has been writen concerning other laborator...

The aim of this study was to analyze the relationship between apolipoprotein E (ApoE) and amyloid β-protein (Aβ) deposits in 29 brains from a series of elderly women, whose intellectual status had been prospectively assessed by the Blessed test score (BTS). In three cases the APOE genotype was ε3/4, in one ε2/2, in 25 ε3/3. ApoE-like immunoreactive...

Astrocytes have been shown to express endothelin (ET) receptors functionally coupled, via different heterotrimeric G proteins, to several intracellular pathways. To assess the relative contribution of each subtype in the astrocytic responses to ET-1, effects of BQ123, an antagonist selective for the ET receptor subtype A (ETA-R), and IRL1620, an ag...

It is not possible to confirm the hypotheses which suggest that many diseases of the human nervous system are due to prions. Indeed, the large number of attempts to transmit degenerative diseases of known and unknown diagnosis to many animal species, and particularly to primates, have largely been unsuccessful. The rare transmission to inoculated a...

It is not possible to confirm the hypotheses which suggest that many diseases of the human nervous system are due to prions. Indeed, the large number of attempts to transmit degenerative diseases of known and unknown diagnosis to many animal species, and particularly to primates, have largely been unsuccessful. The rare transmission to inoculated a...

Cases of Creutzfeldt-Jakob disease recently occurred after long treatments with pituitary extracted human growth hormone (GH). Prion protein (PrP) and glial fibrillary acidic protein (GFAP), an astrocyte-specific marker, both accumulate in the central nervous systems of infected individuals during transmissible subacute spongiform encephalopathies...

Transmissible subacute spongiform encephalopathies (TSSE) are neurodegenerative diseases characterized by the presence of a modified, partially proteinase-resistant host protein, PrPSc, which accumulates in the brains of infected individuals. Recently it has been reported that amphotericin B (AmB) treatment of hamsters infected with scrapie strain...

The biological hallmark of transmissible spongiform encephalopathies is a significant accumulation, in brain, of the scrapie prion protein (PrPsc), often associated with an increased glial fibrillary acidic protein (GFAP) expression. This study was focused on astrocyte gene expression during scrapie development over a period of 172 days in intracer...

The present study was performed on primary cultures of mouse astrocytes and cultures of rat pheochromocytoma PC-12 in order to investigate the regulation of the prion protein (PrP) gene expression in relation to proliferation and differentiation. Treatment of PC-12 cells with interleukin-6 (IL-6) and beta-nerve growth factor (NGF) resulted in induc...

To begin to understand the molecular basis of cases of Creutzfeldt-Jakob disease recently described in young children, the expression of prion protein and glial fibrillary acidic protein (GFAP) mRNAs was investigated during the development of the brain of scrapie-infected newborn mice. Changes in the time course of expression were identified by Nor...

Developmental regulation in mRNAs of three brain proteins has been investigated by Northern blot evaluation in C57BL/6 mice. The mRNAs of two cytoskeletal components, glial fibrillary acidic protein (GFAP) and beta actin, varied significantly, and differently, during brain development (0-56 days postnatal). The beta actin mRNAs peaked at day 1 afte...