Laura Cherchi

I attended the Bachelor’s degree in Biotechnology in the University of Sassari in 2018 with a final score of 110/110 points with the thesis “Microbiological diagnosis of sepsis, investigation on the diffusion of resistance markers”. Subsequently I enrolled in the Molecular and Medical Biotechnology course held in the University of Verona. During this time, I embarked in my first experience of pre-clinical research in the neurobiology laboratory of Prof. Buffelli where I performed experiments on a mice model of stroke and I learned techniques of non-invasive brain stimulation, behavioural tests, morphological analysis of dendritic spines and immunostaining. In 2021 I obtained my Master’s degree in Molecular and Medical Biotechnology in the University of Verona with a final score of 110/110 with the thesis titled “The use of transcranial direct current stimulation for early intervention after brain ischemia: microglia as a key target”. Following this, I completed a 6-months fellowship in the laboratory of Prof. Buffelli where I continued my research in the field of post-stroke brain plasticity and I learned techniques of mice neurosurgery. Between the year 2021 and 2022 I worked with a research contract for 13 months in the neuropsychopharmacology laboratory of Prof. Comai in the San Raffaele hospital for the project “The clock is ticking on schizophrenia: a translational study integrating phenotypic, genomic, microbiome and biomolecular data to overcome disability”. During this time, I learned to perform in vivo techniques of electrophysiology and I deepened my knowledge on mice neurosurgery and behavioural test working with a schizophrenia mice model. I am currently enrolled in my second year of the Experimental Neuroscience PhD program in the University of Milano-Bicocca, under the supervision of Prof. Paola Marmiroli.

PhD research project

The supraspinal pain pathway in animal models of chemotherapy-induced peripheral neuropathy

Neuropathic pain is widely defined as pain caused by a lesion or a disease of the somatosensory system, which includes peripheral nerves and central nervous system structures. Several chemotherapeutic agents’ side effects include peripheral neurotoxicity occurring as pure sensory neuropathy or mixed sensorimotor neuropathy. The neurotoxic effect can appear immediately after the drug administration (acute neurotoxicity) and is generally transitory, but more often symptoms of chronic peripheral neuropathy are reported, that could sometimes lead to the suspension or replacement of the antineoplastic drug. Moreover, CIPN is often associated with neuropathic pain. Currently there is a lack of effective neuroprotective agents recommended to treat or prevent CIPN. Among these chemotherapeutic agents, paclitaxel and bortezomib are the most notable for the incidence of neuropathic pain, leading to numbing, tingling and burning symptoms in a stocking-glove distribution. The central nervous system (CNS) role in the pathogenesis of painful CIPN development needs to be further explored, as the brain may play an important role even if it is protected by brain-blood barrier and the CNS is subjected to circuitry compensation and reorganization after peripheral damage. The anterior cingulate cortex (ACC) is a key structure in the limbic system implicated in the emotional processing of ongoing pain perception and comorbidities associated with neuropathic pain. Some studies have investigated the ACC involvement in the descending inhibitory pain pathway and the periaqueductal grey (PAG), known to be an important region for pain modulation, receives important direct inputs from this forebrain area. The PAG is an important brainstem structure that constitutes the primary control centre for descending pain modulation pathway. The medial Prefrontal Cortex (mPFC) is an area that integrates sensory, affective and attentional components of pain perception. The Mediodorsal thalamic nucleus (MD) plays a pivotal role in the relay of mechanical and thermal nociception information. This project aims to explore the electrophysiological activity of ACC, PAG, mPFC and MD in rodent models of CIPN, investigating the effects of chemotherapeutic drugs with different neuropathic profiles. This project will utilize a Paclitaxel (PTX) model of painful CIPN. Electrophysiological analysis will be performed with single unit in vivo extracellular recordings, where chronic microwire implant electrodes will be lowered in the brain areas of interest. The spontaneous neuronal activity will be recorded from the baseline to the end of the 4 weeks of PTX treatment and over 4 additional weeks of follow-up period. PTX-induced alterations in pain sensitivity will be analysed: mechanical allodynia will be tested with a Dynamic Plantar Aesthesiometer test apparatus by pressing a metal filament with increasing force to the plantar surface of the hind paw. In the end, the pressure required to elicit a paw withdrawal reflex will be recorded to determine the mechanical threshold force. At the end of the experimental time points, samples will be collected from the animals’ brain, spinal cord, caudal nerve and DRGs to conduct histopathological and molecular analysis.