In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related ...cognitive decline, with the most consistent effects against Alzheimer's disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology.
Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out.
The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities.
The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The muscarinic receptor response to acetylcholine regulates the hippocampal-related learning, memory, neural plasticity and the production and processing of the pro-nerve growth factor (proNGF) by ...hippocampal cells. The development and progression of diabetes generate a mild cognitive impairment reducing the functions of the septo-hippocampal cholinergic circuitry, depressing neural plasticity and inducing proNGF accumulation in the brain. Here we demonstrate, in a rat model of early type-1 diabetes, that a physical therapy, the electroacupuncture, counteracts the diabetes-induced deleterious effects on hippocampal physiology by ameliorating hippocampal-related memory functions; recovering the impaired long-term potentiation at the dentate gyrus (DG-LTP) and the lowered expression of the vesicular glutamate transporter 1; normalizing the activity-dependent release of proNGF in diabetic rat hippocampus. Electroacupuncture exerted its therapeutic effects by regulating the expression and activity of M1- and M2-acetylcholine muscarinic receptors subtypes in the dentate gyrus of hippocampus. Our results suggest that a physical therapy based on repetitive sensory stimulation could promote hippocampal neural activity, neuronal metabolism and functions, and conceivably improve the diabetes-induced cognitive impairment. Our data can support the setup of therapeutic protocols based on a better integration between physical therapies and pharmacology for the cure of diabetes-associated neurodegeneration and possibly for Alzheimer's disease.
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In the big data era, artificial intelligence techniques have been applied to tackle traditional issues in the study of neurodegenerative diseases. Despite the progress made in understanding the ...complex (epi)genetics signatures underlying neurodegenerative disorders, performing early diagnosis and developing drug repurposing strategies remain serious challenges for such conditions. In this context, the integration of multi-omics, neuroimaging, and electronic health records data can be exploited using deep learning methods to provide the most accurate representation of patients possible. Deep learning allows researchers to find multi-modal biomarkers to develop more effective and personalized treatments, early diagnosis tools, as well as useful information for drug discovering and repurposing in neurodegenerative pathologies. In this review, we will describe how relevant studies have been able to demonstrate the potential of deep learning to enhance the knowledge of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases through the integration of all sources of biomedical data.
The environmental enrichment (EE) paradigm is widely used to study experience-dependent brain plasticity. Several studies have investigated functional and anatomical EE effects. However, as EE ...effects are different according to cerebral region, cortical layer, dendritic field and morphological index considered, a univocal characterization of neuronal morphological changes following rearing in enriched environments is lacking.
Aim of the present study was to characterize in the rat the effects of EE on the neuronal morphology of frontal and parietal cortical regions, the main target areas of the stimulation provided by the paradigm. Male Wistar rats were housed in an enriched environment for 3.5 months from the 21st postnatal day. For the morphological analysis, biotinylated dextran amine (BDA)-labeled pyramidal neurons were selected from frontal (M1–M2) and parietal (S1–S2) cortical layers III and V. Apical and basal dendritic branching and spines were analyzed using the Sholl method.
Results showed that EE increased branching and spines in both layers of frontal cortex, but had a greater effect on apical arborization. In parietal cortex, EE significantly affected branching and spines in layer III but not layer V neurons, in which only a tendency to be influenced by the rearing conditions was observed in basal arborization.
It is hypothesized that these multifaceted morphological EE effects are connected to the heavy involvement of a sensory-motor circuit engaged in the guidance of voluntary action and in motor learning activated by EE stimulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Converging evidence suggests an association between spatial and music domains. A cerebellar role in music-related information processing as well as in spatial-temporal tasks has been documented. ...Here, we investigated the cerebellar role in the association between spatial and musical domains, by testing performances in embodied (EMR) or abstract (AMR) mental rotation tasks of subjects listening Mozart Sonata K.448, which is reported to improve spatial-temporal reasoning, in the presence or in the absence of continuous theta burst stimulation (cTBS) of the left cerebellar hemisphere. In the absence of cerebellar cTBS, music listening did not influence either MR task, thus not revealing a "Mozart Effect". Cerebellar cTBS applied before musical listening made subjects faster (P = 0.005) and less accurate (P = 0.005) in performing the EMR but not the AMR task. Thus, cerebellar inhibition by TBS unmasked the effect of musical listening on motor imagery. These data support a coupling between music listening and sensory-motor integration in cerebellar networks for embodied representations.
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The cerebellum is involved in motor learning of new procedures both during actual execution of a motor task and during observational training. These processes are thought to depend on the activity of ...a neural network that involves the lateral cerebellum and primary motor cortex (M1). In this study, we used a twin-coil TMS technique to investigate whether execution and observation of a visuomotor procedural learning task is related to modulation of cerebello-motor connectivity. We observed that, at rest, a magnetic conditioning pulse applied over the lateral cerebellum reduced the motor-evoked potentials obtained by stimulating the contralateral M1, indicating activation of a cerebello-motor connection. Furthermore, during procedural learning, cerebellar stimulation resulted in selective facilitation, not inhibition, of contralateral M1 excitability. The effects were evident when motor learning was obtained by actual execution of the task or by observation, but they disappeared if procedural learning had already been acquired by previous observational training. These results indicate that changes in cerebello-motor connectivity occur in relation to specific phases of procedural learning, demonstrating a complex pattern of excitatory and inhibitory drives modulated across time.
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Observing another person performing a complex action accelerates the observer's acquisition of the same action and limits the time-consuming process of learning by trial and error. Observational ...learning makes an interesting and potentially important topic in the developmental domain, especially when disorders are considered. The implications of studies aimed at clarifying whether and how this form of learning is spared by pathology are manifold. We focused on a specific population with learning and intellectual disabilities, the individuals with Williams syndrome. The performance of twenty-eight individuals with Williams syndrome was compared with that of mental age- and gender-matched thirty-two typically developing children on tasks of learning of a visuo-motor sequence by observation or by trial and error. Regardless of the learning modality, acquiring the correct sequence involved three main phases: a detection phase, in which participants discovered the correct sequence and learned how to perform the task; an exercise phase, in which they reproduced the sequence until performance was error-free; an automatization phase, in which by repeating the error-free sequence they became accurate and speedy. Participants with Williams syndrome beneficiated of observational training (in which they observed an actor detecting the visuo-motor sequence) in the detection phase, while they performed worse than typically developing children in the exercise and automatization phases. Thus, by exploiting competencies learned by observation, individuals with Williams syndrome detected the visuo-motor sequence, putting into action the appropriate procedural strategies. Conversely, their impaired performances in the exercise phases appeared linked to impaired spatial working memory, while their deficits in automatization phases to deficits in processes increasing efficiency and speed of the response. Overall, observational experience was advantageous for acquiring competencies, since it primed subjects' interest in the actions to be performed and functioned as a catalyst for executed action.
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The relationship between physical exercise and improvement in specific cognitive domains in children and adolescents who play sport has been recently reported, although the effects on visuospatial ...abilities have not yet been well explored. This study is aimed at evaluating in school-age children practicing artistic gymnastics the visuospatial memory by using a table version of the Radial Arm Maze (table-RAM) and comparing their performances with those ones who do not play any sport. The visuospatial performances of 14 preadolescent girls practicing artistic gymnastics aged between 7 and 10 years and those of 14 preadolescent girls not playing any sport were evaluated in the table-RAM forced-choice paradigm that allows disentangling short-term memory from working memory abilities. Data showed that the gymnasts obtained better performances than control group mainly in the parameters evaluating working memory abilities, such as within-phase errors and spatial span. Our findings emphasizing the role of physical activity on cognitive performances impel to promote physical exercise in educational and recreational contexts as well as to analyse the impact of other sports besides gymnastics on cognitive functioning.
The analysis of sequences of words and prosody, meter, and rhythm provided in an interview addressing the capacity to identify and describe emotions represents a powerful tool to reveal emotional ...processing. The ability to express and identify emotions was analyzed by means of the Toronto Structured Interview for Alexithymia (TSIA), and TSIA transcripts were analyzed by Natural Language Processing to shed light on verbal features. The brain correlates of the capacity to translate emotional experience into words were determined through cortical thickness measures. A machine learning methodology proved that individuals with deficits in identifying and describing emotions (n = 7) produced language distortions, frequently used the present tense of auxiliary verbs, and few possessive determiners, as well as scarcely connected the speech, in comparison to individuals without deficits (n = 7). Interestingly, they showed high cortical thickness at left temporal pole and low at isthmus of the right cingulate cortex. Overall, we identified the neuro-linguistic pattern of the expression of emotional experience.
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