Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice.

The microbiota-gut-brain axis (MGBA) regulates the reciprocal interaction between chronic inflammatory bowel and psychiatric disorders. This interaction involves multiple pathways that are highly debated. We examined the behavioural, biochemical and electrophysiological alterations, as well as gut microbiota composition in a model of antibiotic-induced experimental dysbiosis. Inflammation of the small intestine was also assessed. Mice were exposed to a mixture of antimicrobials for 2weeks. Afterwards, they received Lactobacillus casei DG (LCDG) or a vehicle for up to 7days via oral gavage. Perturbation of microbiota was accompanied by a general inflammatory state and alteration of some endocannabinoidome members in the gut. Behavioural changes, including increased immobility in the tail suspension test and reduced social recognition were observed, and were associated with altered BDNF/TrkB signalling, TRPV1 phosphorylation and neuronal firing in the hippocampus. Moreover, morphological rearrangements of non-neuronal cells in brain areas controlling emotional behaviour were detected. Subsequent probiotic administration, compared with vehicle, counteracted most of these gut inflammatory, behavioural, biochemical and functional alterations. Interestingly, levels of Lachnospiraceae were found to significantly correlate with the behavioural changes observed in dysbiotic mice. Our findings clarify some of the biomolecular and functional modifications leading to the development of affective disorders associated with gut microbiota alterations.

Ultrasound and analysis of the deformation patterns of the masseter muscle: comparing surgical anatomy, ultrasound and functional anatomy.

PURPOSE: We have tried to demonstrate whether the analysis of the muscle strain allows us to identify the three distinct functional areas of the architecture of the masseter, as one would see them by performing or viewing an anatomical dissection of said muscle, and whether these sections have behave differently in terms of origin and coping of the strain they face (quantitative analysis). MATERIALS AND METHODS: This work has been elaborated by the use of an ultrasound machine (MicrUs ext-1H Telemed Medical Systems Milano) and a linear probe (L12-5l40S-3 5-12 MHz 40 mm) which allowed us to record a 45 frame per second video (DCM). Videos has been elaborated by use of an ultrasound machine (MicrUs ext-1H Telemed Medical Systems Milano) and a linear probe (L12-5l40S-3 5-12 MHz 40 mm) which allowed us to record a 45 frame per second video (DCM). We applied to the resulting video a software (Mudy 1.7.7.2 AMID Sulmona Italy) for the analysis of muscle deformation patters (contraction, dilatation, cross-plane, vertical strain, horizontal strain, vertical shear, horizontal shear, horizontal displacement, vertical displacement). The number of videos of masseter muscles in contraction at maximum exertion due to dental clenching made during this research is around 12,000. Out of these we chose 1,200 videos which examine 200 patients (100 females, 100 males). RESULTS: The deformation pattern analysis of the skeletal muscle on ultrasound basis seems to be an adequate instrument to use during the investigation of the functional structure of the masseter muscle given its ability to highlight the distinct activity of each separate part of the muscle. CONCLUSIONS: Moreover the strain does not apply to the muscle uniformly; instead it varies according to the observed area.

Management and control of isotonic contraction generated stress: evaluation of masseter muscle deformation pattern by means of ecography.

PURPOSE: The objective of the following study is to observe the behavior of the six layers of the masseter during an isometric contraction at maximum exertion with the deformation pattern analysis method. MATERIALS AND METHODS: This study has been conducted by use of an ultrasound machine (MicrUs ext-1H Telemed Medical Systems Milano) and a linear probe (L12-5l40S-3 5-12 MHz 40 mm) which allowed us to record a video (DCM) comprised of 45 frames per second. The probe was fixed to a brace and the patient was asked to clench their teeth as hard as possible, obtain the muscle's maximum exertion, for 5 seconds three times, with 30 seconds intervals in between. Both right and left masseter muscles were analyzed. Then we applied to the resulting video a software (Mudy 1.7.7.2 AMID Sulmona Italy) for the analysis of muscle deformation patterns (contraction, dilatation, cross-plane, vertical strain, horizontal strain, vertical shear, horizontal shear, horizontal displacement, vertical displacement). The number of videos of masseter muscles in contraction at maximum exertion due to dental clenching made during this research is around 12,000. Out of these we chose 1,200 videos which examine 200 patients (100 females, 100 males). RESULTS: The analysis of the deformation patterns of the masseter allows us to observe how the six layers of the muscle have different and specific functions each, which vary depending on the applied force (application point, magnitude and direction) so that we find it impossible to assign to one of the three sections of the muscle a mechanical predominance. Therefore it appears that the three parts of the muscle have specific and synergistic tasks.

Analysis of masseter deformation patterns during a maximum exertion clenching in patients with unilateral chewing.

PURPOSE: The aim of the following study is to examine both masseter muscles (left/right) in a group of patients suffering from unilateral chewing during a maximum exertion isometric contraction using the deformation pattern analysis of ultrasound videos and compare them with the results obtained by studying patients with alternate bilateral chewing patterns. MATERIALS AND METHODS: This study has been conducted by use of an ultrasound machine and a linear probe which allowed us to record a video (DCM) comprised of 45 frames per second (MicrUs ext-1H Telemed Medical Systems Milano) and a linear probe (L12-5l40S-3 5-12 MHz 40 mm). The probe was fixed to a brace and the patients were asked to clench their teeth as hard as possible, obtain the muscle's maximum exertion, for 5 seconds three times, with 30 seconds intervals in between. Both right and left masseter muscles were analyzed. We applied to the ultrasound video a dedicated software (Mudy 1.7.7.2 AMID Sulmona Italy) for the analysis of muscle deformation patterns. The total number of patients for this study is 150. Out of this number, 50 belong to Group A, mono lateral chewing on the left side arch, and 50 to Group B, mono lateral chewing on the right side arch. The remains patients belong to Group C, bilateral alternate chewing. The deformation pattern analysis of the skeletal muscles on ultrasound videos allows us to highlight with ease the clear difference in the clenching capabilities and strain management between the dominant masseter and the subordinate masseter in a unilaterally chewing patient. RESULTS: In the sample investigated both in Group A and Group B the unilateral chewing is associated with a series of parameters (number, shape, volume, position and orientation of the teeth) and is also associated with the extension of the cutting surface really available.

Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice.

BACKGROUND: Enhanced supraspinal glutamate levels following nerve injury are associated with pathophysiological mechanisms responsible for neuropathic pain. Chronic pain can interfere with specific brain areas involved in glutamate-dependent neuropsychological processes, such as cognition, memory, and decision-making. The medial prefrontal cortex (mPFC) is thought to play a critical role in pain-related depression and anxiety, which are frequent co-morbidities of chronic pain. Using an animal model of spared nerve injury (SNI) of the sciatic nerve, we assess bio-molecular modifications in glutamatergic synapses in the mPFC that underlie neuropathic pain-induced plastic changes at 30 days post-surgery. Moreover, we examine the effects of palmitoylethanolamide (PEA) administration on pain-related behaviours, as well as the cortical biochemical and morphological changes that occur in SNI animals. RESULTS: At 1 month, SNI was associated with mechanical and thermal hypersensitivity, as well as depression-like behaviour, cognitive impairments, and obsessive-compulsive activities. Moreover, we observed an overall glutamate synapse modification in the mPFC, characterized by changes in synaptic density proteins and amino acid levels. Finally, with regard to the resolution of pain and depressive-like syndrome in SNI mice, PEA restored the glutamatergic synapse proteins and changes in amino acid release. CONCLUSIONS: Given the potential role of the mPFC in pain mechanisms, our findings may provide novel insights into neuropathic pain forebrain processes and indicate PEA as a new pharmacological tool to treat neuropathic pain and the related negative affective states. Graphical Abstract Palmitoylethanolamide: a new pharmacological tool to treat neuropathic pain and the related negative affective states.

Alterations of brain and cerebellar proteomes linked to Aß and tau pathology in a female triple-transgenic murine model of Alzheimer's disease.

The triple-transgenic Alzheimer (3 × Tg-AD) mouse expresses mutant PS1(M146V), APP(swe), and tau(P301L) transgenes and progressively develops plaques and neurofibrillary tangles with a temporal- and region-specific profile that resembles the neuropathological progression of Alzheimer's disease (AD). In this study, we used proteomic approaches such as two-dimensional gel electrophoresis and mass spectrometry to investigate the alterations in protein expression occurring in the brain and cerebellum of 3 × Tg-AD and presenilin-1 (PS1) knock-in mice (animals that do not develop Aß- or tau-dependent pathology nor cognitive decline and were used as control). Finally, using the Ingenuity Pathway Analysis we evaluated novel networks and molecular pathways involved in this AD model. We identified several differentially expressed spots and analysis of 3 × Tg-AD brains showed a significant downregulation of synaptic proteins that are involved in neurotransmitter synthesis, storage and release, as well as a set of proteins that are associated with cytoskeleton assembly and energy metabolism. Interestingly, in the cerebellum, a structure not affected by AD, we found an upregulation of proteins involved in carbohydrate metabolism and protein catabolism. Our findings help to unravel the pathogenic brain mechanisms set in motion by mutant amyloid precursor protein (APP) and hyperphosphorylated tau. These data also reveal cerebellar pathways that may be important to counteract the pathogenic actions of Aß and tau, and ultimately offer novel targets for therapeutic intervention.