Roberta Marongiu

Weill Cornell Medicine | Cornell · Department of Neurological Surgery

Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)–mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor–Cre drivers resulted in motor freezing when placed in...

Protocol for processing 30um mouse brain sections for immunolabeling.

To test for 6-OHDA lesion efficiency, rotational behaviors are assessed while mice are under the effects of apomorphine. This test is run during the dark phase of light cycle. Experiments are performed by an examiner blinded to treatment groups.

This protocol is for injection of AAV into a mouse brain using a stereotactic frame and Hamilton syringe.

Lesion of the medial forebrain bundle using 6-OHDA to induce parkinsonian-like deficits in mice.

The glucose tolerance test is performed to determine how quickly the glucose is cleared from the blood. It is used to test for diabetes or insulin resistance.

Dementia is often characterized by age-dependent cerebrovascular pathology, neuroinflammation, and cognitive deficits with notable sex differences in risk, disease onset, progression and severity. Women bear a disproportionate burden of dementia, and the onset of menopause (i.e., perimenopause) may be a critical period conferring increased suscepti...

The glucose tolerance test is performed to determine how quickly the glucose is cleared from the blood. It is used to test for diabetes or insulin resistance.

This test is used to check for signs of constipation

The Cylinder test is used to evaluate locomotor asymmetry in rodent models

This test is used to check for possible signs of constipation and alteration in the gut transit

The challenging beam test is used to measure motor performance, coordination, and balance

Here we report a novel suite of magnetogenetic tools, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. AAV-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine 2a receptor-cre driver mice resulted in motor freezing when placed in an MRI...

INTRODUCTION: Primary nociceptors are the first neurons involved in processing normal and pathological pain. Novel biological approaches such as gene therapies targeting these neurons have great potential, but delivery can be challenging when open or percutaneous infusion into the dorsal root ganglion (DRG) is needed. METHODS: Primary nociceptor...

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, affecting approximately 6-7 million patients worldwide. Involuntary hand tremor (IHT), one of the cardinal motor symptoms of PD, is extremely debilitating to patients reducing their quality of life. In this study, we combined neuroscience together with the nascent fi...

The menopause is a midlife endocrinological process that greatly affects women’s central nervous system functions. Over the last 2 decades numerous clinical studies have addressed the influence of ovarian hormone decline on neurological disorders like Parkinson’s disease and Alzheimer’s disease. However, the findings in support of a role for age at...

Hypertension is a risk factor for neurodegenerative disorders involving inflammation and inflammatory cytokine-producing brain cells (microglia and astrocytes) in the hippocampus and medial prefrontal cortex (mPFC). Here we investigated the effect of slow-pressor angiotensin II (AngII) on gliosis in the hippocampus and mPFC of young adult (2-mo-old...

This protocol is designed to perform fluorescent immunolabelling on neuronal primary culture after PFF incubation. The labelling of phosphorylated Alpha-synuclein is considered as a marker of the PFF toxicity and should be performed to test the PFF before in vivo injection. See protocol for PFF preparation https://www.protocols.io/view/production-o...

This behavioral test is used to assess motor deficits in mouse models of Parkinson's disease.

This behavior test is used to assess motor coordination in mice.

qPCR standards for AAV tittering document annex to protocol "AAV Purification Protocol with Iodixanol gradient"

A lack of comprehensive mapping of ganglionic inputs into the pancreas and of technology for the modulation of the activity of specific pancreatic nerves has hindered the study of how they regulate metabolic processes. Here we show that the pancreas-innervating neurons in sympathetic, parasympathetic and sensory ganglia can be mapped in detail by u...

Neuronal inputs from central nervous system (CNS) are essential in regulating pancreatic endocrine function. It has been shown that perturbation of CNS activity alters pancreatic hormone release. CNS and peripheral organs constantly communicate through the peripheral nervous system (PNS), which can be divided into autonomic efferent (parasympatheti...

Instructions to perform ISH using RNAscope kit from acdbio company

Introduction Modified ion channels provide powerful opportunities to regulate neuronal circuits with light (optogenetics) or drugs (chemogenetics). Magnetogenetics uses a modified Trpv1 receptor fused to a ferritin nanoparticle, which permits channel control by a magnetic field, allowing more rapid neuronal regulation than chemogenetics while elimi...

Introduction: Peripheral and central nervous system inflammation have been linked to the classic symptoms of Parkinson's disease (PD) and Alzheimer's disease (AD). However, it remains unclear whether the analysis of routine systemic inflammatory markers could represent a useful prediction tool to identify clinical subtypes in patients with Parkins...

Multidisciplinary neurotechnology holds the promise of understanding and non-invasively treating neurodegenerative diseases. In this preclinical trial on Parkinson's disease (PD), we combined neuroscience together with the nascent field of medical virtual reality and generated several important observations. First, we established the Oculus Rift vi...

Despite decades of extensive research efforts, efficacious therapies for Alzheimer’s disease (AD) are lacking. The multi-factorial nature of AD neuropathology and symptomatology has taught us that a single therapeutic approach will most likely not fit all. Women constitute ~70% of the affected AD population, and pathology and rate of symptoms progr...

In Parkinson disease (PD), a complex neurodegenerative disorder that affects nearly 10 million people worldwide, motor skills are significantly impaired. However, onset and progression of motor deficits and the neural correlates of these deficits are poorly understood. We used a genetic mouse model of PD (Pink1 -/-), with phenotypic similarities to...

Significance Medications for Parkinson’s disease (PD) are designed to replace lost dopamine. Although effective, they often cause abnormal involuntary movements (AIMs), also called dyskinesias, which can be difficult to resolve without worsening PD symptoms. We report that p11, a small protein necessary for neurotransmitter receptor function, is cr...

Significance Parkinson’s disease (PD) is symptomatically treated with levodopa (L-DOPA), but this treatment often results in disabling dyskinesias. Subchronic L-DOPA increases striatal levels of adaptor protein, p11. Using experimental mouse models of Parkinsonism, we report here that global p11 knockout mice show reduced therapeutic responses to L...

Background The high rate of comorbidity between depression and cocaine addiction suggests shared molecular mechanisms and anatomical pathways. Limbic structures, such as the Nucleus Accumbens (NAc), play a crucial role in both disorders, yet how different cell types within these structures contribute to the pathogenesis remains elusive. Downregulat...

Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented her...

Mutations in the PTEN-induced putative kinase1 (PINK1) represent the second most frequent cause of autosomal recessive Parkinson's disease. The PINK1 protein mainly localizes to mitochondria and interacts with a variety of proteins, including the pro-autophagy protein beclin1 and the ubiquitin-ligase parkin. Upon stress conditions, PINK1 is known t...

The advent of viral gene therapy technology has contributed greatly to the study of a variety of medical conditions, and there is increasing promise for clinical translation of gene therapy into human treatments. Adeno-associated viral (AAV) vectors provide one of the more promising approaches to gene delivery, and have been used extensively over t...

Mutations in the PINK1 gene cause autosomal recessive Parkinson's disease. The PINK1 gene encodes a protein kinase that is mitochondrially cleaved to generate two mature isoforms. In addition to its protective role against mitochondrial dysfunction and apoptosis, PINK1 is also known to regulate mitochondrial dynamics acting upstream of the PD-relat...

Parkinson's disease (PD) is characterized by accumulation of alpha-synuclein (alpha-syn) and degeneration of neuronal populations in cortical and subcortical regions. Mitochondrial dysfunction has been considered a potential unifying factor in the pathogenesis of the disease. Mutations in genes linked to familial forms of PD, including SNCA encodin...

Heterozygous rare variants in the PINK1 gene, as well as in other genes causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large studies that assessed the freq...

Autosomal recessive parkinsonism is a genetic condition closely resembling Parkinson disease, the only distinguishing features being an earlier age at onset and a slower disease progression. Three causative genes have been identified so far. While exon rearrangements are frequently encountered in the Parkin gene, most PINK1 mutations are represente...

To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019...

To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019...

We analyzed the PINK1 gene in 58 patients with early-onset Parkinsonism and detected the homozygous mutation W437X in I patient. The clinical phenotype was characterized by early onset (22 years of age), good response to levodopa, early fluctuations and dyskinesias, and psychiatric symptoms. The mother, heterozygote for W437X mutation, was affected...

We have recently reported homozygous mutations in the PINK1 gene in three consanguineous families with early-onset parkinsonism (EOP) linked to the PARK6 locus. To further evaluate the pathogenic role of PINK1 in EOP and to draw genotype-phenotype correlates, we performed PINK1 mutation analysis in a cohort of Italian EOP patients, mostly sporadic,...