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Article: Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring.

Golini, Elisabetta / Rigamonti, Mara / Raspa, Marcello / Scavizzi, Ferdinando / Falcone, Germana / Gourdon, Genevieve / Mandillo, Silvia

Frontiers in behavioral neuroscience

2023 Volume 17, Page(s) 1130055

Abstract: Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3'-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms ... ...

Abstract	Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3'-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-respiratory problems, hypersomnia, cognitive dysfunction and behavioral abnormalities. Sleep-related disturbances are among the most reported symptoms that negatively affect the quality of life of patients and that are present in early and adult-onset forms of the disease. DMSXL mice carry a mutated human
Language	English
Publishing date	2023-03-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2023.1130055
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Article ; Online: Data repurposing from digital home cage monitoring enlightens new perspectives on mouse motor behaviour and reduction principle.

Fuochi, Sara / Rigamonti, Mara / Raspa, Marcello / Scavizzi, Ferdinando / de Girolamo, Paolo / D'Angelo, Livia

Scientific reports

2023 Volume 13, Issue 1, Page(s) 10851

Abstract: In this longitudinal study we compare between and within-strain variation in the home-cage spatial preference of three widely used and commercially available mice strains-C57BL/6NCrl, BALB/cAnNCrl and CRL:CD1(ICR)-starting from the first hour post cage- ... ...

Abstract	In this longitudinal study we compare between and within-strain variation in the home-cage spatial preference of three widely used and commercially available mice strains-C57BL/6NCrl, BALB/cAnNCrl and CRL:CD1(ICR)-starting from the first hour post cage-change until the next cage-change, for three consecutive intervals, to further profile the circadian home-cage behavioural phenotypes. Cage-change can be a stressful moment in the life of laboratory mice, since animals are disturbed during the sleeping hours and must then rapidly re-adapt to a pristine environment, leading to disruptions in normal motor patterns. The novelty of this study resides in characterizing new strain-specific biological phenomena, such as activity along the cage walls and frontality, using the vast data reserves generated by previous experimental data, thus introducing the potential and exploring the applicability of data repurposing to enhance Reduction principle when running in vivo studies. Our results, entirely obtained without the use of new animals, demonstrate that also when referring to space preference within the cage, C57BL/6NCrl has a high variability in the behavioural phenotypes from pre-puberty until early adulthood compared to BALB/cAnNCrl, which is confirmed to be socially disaggregated, and CRL:CD1(ICR) which is conversely highly active and socially aggregated. Our data also suggest that a strain-oriented approach is needed when defining frequency of cage-change as well as maximum allowed animal density, which should be revised, ideally under the EU regulatory framework as well, according to the physiological peculiarities of the strains, and always avoiding the "one size fits all" approach.
MeSH term(s)	Animals ; Mice ; Longitudinal Studies ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Running ; Circadian Rhythm/physiology ; Behavior, Animal/physiology
Language	English
Publishing date	2023-07-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-37464-8
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Article: Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice.

Faydaver, Melisa / El Khatib, Mohammad / Russo, Valentina / Rigamonti, Mara / Raspa, Marcello / Di Giacinto, Oriana / Berardinelli, Paolo / Mauro, Annunziata / Scavizzi, Ferdinando / Bonaventura, Fabrizio / Mastrorilli, Valentina / Valbonetti, Luca / Barboni, Barbara

Frontiers in veterinary science

2023 Volume 10, Page(s) 1281040

Abstract: Introduction: Tendon disorders present significant challenges in the realm of musculoskeletal diseases, affecting locomotor activity and causing pain. Current treatments often fall short of achieving complete functional recovery of the tendon. It is ... ...

Abstract	Introduction: Tendon disorders present significant challenges in the realm of musculoskeletal diseases, affecting locomotor activity and causing pain. Current treatments often fall short of achieving complete functional recovery of the tendon. It is crucial to explore, in preclinical research, the pathways governing the loss of tissue homeostasis and its regeneration. In this context, this study aimed to establish a correlation between the unbiased locomotor activity pattern of CRL:CD1 (ICR) mice exposed to uni- or bilateral Achilles tendon (AT) experimental injuries and the key histomorphometric parameters that influence tissue microarchitecture recovery. Methods: The study involved the phenotyping of spontaneous and voluntary locomotor activity patterns in male mice using digital ventilated cages (DVC Results and discussion: The results revealed significant variations in activity levels based on the type of tendon injury and access to running wheels. Notably, mice with bilateral lesions and unrestricted wheel access exhibited significantly higher activity after surgery. Extracellular matrix (ECM) remodeling, including COL1 deposition and organization, blood vessel remodeling, and metaplasia, as well as cytological tendon parameters, such as cell alignment and angle deviation were enhanced in surgical (bilateral lesion) and husbandry (free access to wheels) groups. Interestingly, correlation matrix analysis uncovered a strong relationship between locomotion and microarchitecture recovery (cell alignment and angle deviation) during tendon healing. Overall, this study highlights the potential of using mice activity metrics obtained from a home-cage monitoring system to predict tendon microarchitecture recovery at both cellular and ECM levels. This provides a scalable experimental setup to address the challenging topic of tendon regeneration using innovative and animal welfare-compliant strategies.
Language	English
Publishing date	2023-12-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1281040
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Article ; Online: Phenotyping spontaneous locomotor activity in inbred and outbred mouse strains by using Digital Ventilated Cages.

Fuochi, Sara / Rigamonti, Mara / Iannello, Fabio / Raspa, Marcello / Scavizzi, Ferdinando / de Girolamo, Paolo / D'Angelo, Livia

Lab animal

2021 Volume 50, Issue 8, Page(s) 215–223

Abstract: Mouse strains differ markedly in all behaviors, independently of their genetic background. We undertook this study to disentangle the diurnal activity and feature key aspects of three non-genetically altered mouse strains widely used in research, C57BL/ ... ...

Abstract	Mouse strains differ markedly in all behaviors, independently of their genetic background. We undertook this study to disentangle the diurnal activity and feature key aspects of three non-genetically altered mouse strains widely used in research, C57BL/6NCrl (inbred), BALB/cAnNCrl (inbred) and CRL:CD1(ICR) (outbred). With this aim, we conducted a longitudinal analysis of the spontaneous locomotor activity of the mice during a 24-h period for 2 months, in two different periods of the year to reduce the seasonality effect. Mice (males and females) were group-housed in Digital Ventilated Cages (Tecniplast), mimicking standard housing conditions in research settings and avoiding the potential bias provided in terms of locomotor activity by single housing. The recorded locomotor activity was analyzed by relying on different and commonly used circadian metrics (i.e., day and night activity, diurnal activity, responses to lights-on and lights-off phases, acrophase and activity onset and regularity disruption index) to capture key behavioral responses for each strain. Our results clearly demonstrate significant differences in the circadian activity of the three selected strains, when comparing inbred versus outbred as well as inbred strains (C57BL/6NCrl versus BALB/cAnNCrl). Conversely, males and females of the same strain displayed similar motor phenotypes; significant differences were recorded only for C57BL/6NCrl and CRL:CD1(ICR) females, which displayed higher average locomotor activity from prepuberty to adulthood. All strain-specific differences were further confirmed by an unsupervised machine learning approach. Altogether, our data corroborate the concept that each strain behaves under characteristic patterns, which needs to be taken into consideration in the study design to ensure experimental reproducibility and comply with essential animal welfare principles.
MeSH term(s)	Animal Welfare ; Animals ; Female ; Locomotion ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Inbred Strains ; Reproducibility of Results
Language	English
Publishing date	2021-06-21
Publishing country	United States
Document type	Journal Article
ISSN	1548-4475
ISSN (online)	1548-4475
DOI	10.1038/s41684-021-00793-0
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Article ; Online: Antibody gene transfer treatment drastically improves epidermal pathology in a keratitis ichthyosis deafness syndrome model using male mice.

Peres, Chiara / Sellitto, Caterina / Nardin, Chiara / Putti, Sabrina / Orsini, Tiziana / Di Pietro, Chiara / Marazziti, Daniela / Vitiello, Adriana / Calistri, Arianna / Rigamonti, Mara / Scavizzi, Ferdinando / Raspa, Marcello / Zonta, Francesco / Yang, Guang / White, Thomas W / Mammano, Fabio

EBioMedicine

2023 Volume 89, Page(s) 104453

Abstract: Background: Keratitis ichthyosis deafness (KID) syndrome is a rare disorder caused by hemichannel (HC) activating gain-of-function mutations in the GJB2 gene encoding connexin (Cx) 26, for which there is no cure, or current treatments based upon the ... ...

Abstract	Background: Keratitis ichthyosis deafness (KID) syndrome is a rare disorder caused by hemichannel (HC) activating gain-of-function mutations in the GJB2 gene encoding connexin (Cx) 26, for which there is no cure, or current treatments based upon the mechanism of disease causation. Methods: We applied Adeno Associated Virus (AAV) mediated mAb gene transfer (AAVmAb) to treat the epidermal features of KID syndrome with a well-characterized HC blocking antibody using male mice of a murine model that replicates the skin pathology of the human disease. Findings: We demonstrate that in vivo AAVmAb treatment significantly reduced the size and thickness of KID lesions, in addition to blocking activity of mutant HCs in the epidermis in vivo. We also show that AAVmAb treatment eliminated abnormal keratinocyte proliferation and enlarged cell size, decreased apoptosis, and restored the normal distribution of keratin expression. Interpretation: Our findings reinforce the critical role played by increased HC activity in the skin pathology associated with KID syndrome. They also underscore the clinical potential of anti-HC mAbs coupled with genetic based delivery systems for treating the underlying mechanistic basis of this disorder. Inhibition of HC activity is an ideal therapeutic target in KID syndrome, and the genetic delivery of mAbs targeted against mutant HCs could form the basis of new therapeutic interventions to treat this incurable disease. Funding: Fondazione Telethon grant GGP19148 and University of Padova grant Prot. BIRD187130 to FM; Foundation for Ichthyosis and Related Skin Types (FIRST) and National Institutes of Health grant EY 026911 to TWW.
MeSH term(s)	Animals ; Male ; Mice ; Antibodies ; Connexins/genetics ; Deafness/genetics ; Epidermis/metabolism ; Gene Transfer Techniques ; Ichthyosis/genetics ; Ichthyosis/metabolism ; Ichthyosis/pathology ; Keratitis/genetics ; Keratitis/metabolism ; Keratitis/pathology ; Mutation
Chemical Substances	Antibodies ; Connexins ; Gjb2 protein, mouse
Language	English
Publishing date	2023-02-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104453
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Article: A Non-invasive Digital Biomarker for the Detection of Rest Disturbances in the SOD1G93A Mouse Model of ALS.

Golini, Elisabetta / Rigamonti, Mara / Iannello, Fabio / De Rosa, Carla / Scavizzi, Ferdinando / Raspa, Marcello / Mandillo, Silvia

Frontiers in neuroscience

2020 Volume 14, Page(s) 896

Abstract: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects both central and peripheral nervous system, leading to the degeneration of motor neurons, which eventually results in muscle atrophy, paralysis, and death. Sleep ... ...

Abstract	Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects both central and peripheral nervous system, leading to the degeneration of motor neurons, which eventually results in muscle atrophy, paralysis, and death. Sleep disturbances are common in patients with ALS, leading to even further deteriorated quality of life. Investigating methods to potentially assess sleep and rest disturbances in animal models of ALS is thus of crucial interest. We used an automated home cage monitoring system (DVC
Language	English
Publishing date	2020-09-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2020.00896
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Article ; Online: Doxycycline rescues recognition memory and circadian motor rhythmicity but does not prevent terminal disease in fatal familial insomnia mice.

Lavigna, Giada / Masone, Antonio / Bouybayoune, Ihssane / Bertani, Ilaria / Lucchetti, Jacopo / Gobbi, Marco / Porcu, Luca / Zordan, Stefano / Rigamonti, Mara / Imeri, Luca / Restelli, Elena / Chiesa, Roberto

Neurobiology of disease

2021 Volume 158, Page(s) 105455

Abstract: Fatal familial insomnia (FFI) is a dominantly inherited prion disease linked to the D178N mutation in the gene encoding the prion protein (PrP). Symptoms, including insomnia, memory loss and motor abnormalities, appear around 50 years of age, leading to ... ...

Abstract	Fatal familial insomnia (FFI) is a dominantly inherited prion disease linked to the D178N mutation in the gene encoding the prion protein (PrP). Symptoms, including insomnia, memory loss and motor abnormalities, appear around 50 years of age, leading to death within two years. No treatment is available. A ten-year clinical trial of doxycycline (doxy) is under way in healthy individuals at risk of FFI to test whether presymptomatic doxy prevents or delays the onset of disease. To assess the drug's effect in a tractable disease model, we used Tg(FFI-26) mice, which accumulate aggregated and protease-resistant PrP in their brains and develop a fatal neurological illness highly reminiscent of FFI. Mice were treated daily with 10 mg/kg doxy starting from a presymptomatic stage for twenty weeks. Doxy rescued memory deficits and restored circadian motor rhythmicity in Tg(FFI-26) mice. However, it did not prevent the onset and progression of motor dysfunction, clinical signs and progression to terminal disease. Doxy did not change the amount of aggregated and protease-resistant PrP, but reduced microglial activation in the hippocampus. Presymptomatic doxy treatment rescues cognitive impairment and the motor correlates of sleep dysfunction in Tg(FFI-26) mice but does not prevent fatal disease.
MeSH term(s)	Animals ; Brain/pathology ; Circadian Rhythm/drug effects ; Disease Progression ; Doxycycline/pharmacology ; Doxycycline/therapeutic use ; Insomnia, Fatal Familial/drug therapy ; Insomnia, Fatal Familial/genetics ; Insomnia, Fatal Familial/pathology ; Memory/drug effects ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Psychomotor Performance/drug effects ; Recognition, Psychology/drug effects
Chemical Substances	Doxycycline (N12000U13O)
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2021.105455
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Article ; Online: Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle.

Glia

2021 Volume 70, Issue 1, Page(s) 89–105

Abstract: Microglia, the brain's resident macrophages, actively contribute to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity. While several studies demonstrated different roles for astrocytes ... ...

Abstract	Microglia, the brain's resident macrophages, actively contribute to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity. While several studies demonstrated different roles for astrocytes in sleep, the contribution of microglia in the regulation of sleep/wake cycle and in the modulation of synaptic activity in the different day phases has not been deeply investigated. Using light as a zeitgeber cue, we studied the effects of microglial depletion with the colony stimulating factor-1 receptor antagonist PLX5622 on the sleep/wake cycle and on hippocampal synaptic transmission in male mice. Our data demonstrate that almost complete microglial depletion increases the duration of NREM sleep and reduces the hippocampal excitatory neurotransmission. The fractalkine receptor CX3CR1 plays a relevant role in these effects, because cx3cr1
MeSH term(s)	Animals ; CX3C Chemokine Receptor 1/genetics ; CX3C Chemokine Receptor 1/metabolism ; Hippocampus/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microglia/metabolism ; Neurons/metabolism ; Sleep ; Synaptic Transmission
Chemical Substances	CX3C Chemokine Receptor 1
Language	English
Publishing date	2021-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639414-0
ISSN	1098-1136 ; 0894-1491
ISSN (online)	1098-1136
ISSN	0894-1491
DOI	10.1002/glia.24090
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Article: Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring.

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Article ; Online: Data repurposing from digital home cage monitoring enlightens new perspectives on mouse motor behaviour and reduction principle.

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Article: Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice.

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Article ; Online: Phenotyping spontaneous locomotor activity in inbred and outbred mouse strains by using Digital Ventilated Cages.

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Article ; Online: Antibody gene transfer treatment drastically improves epidermal pathology in a keratitis ichthyosis deafness syndrome model using male mice.

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Article: A Non-invasive Digital Biomarker for the Detection of Rest Disturbances in the SOD1G93A Mouse Model of ALS.

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Article ; Online: Doxycycline rescues recognition memory and circadian motor rhythmicity but does not prevent terminal disease in fatal familial insomnia mice.

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Article ; Online: Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle.

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