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  • Open access
  • 107 Reads
Bizarre behaviors limit exploratory activity and impair spontaneous gait performance in aged mice with AD pathology

Age-related behavioral changes in older mice develop similarly to older people, but their shorter life spans provide an exceptional experimental gerontology scenario. In the 6-month-old 3xTg-AD mice model for Alzheimer's disease (AD), compared to C57BL/6 wildtype, we previously described increased bizarre (disruptive) behaviors related to psychiatric and neurological disorders when confronting new and unfamiliar environments. We evaluated spontaneous gait and the exploratory activity at old age in the present work, using 16-month-old mice. Male sex was chosen since sex-dependent psychomotor effects of aging are stronger in C57BL/6 males than females, and at this age, male 3xTg-AD mice are close to an end-of-life status due to increased mortality rates. Mice's behavior was evaluated in a transparent test box during the neophobia response. The latency to start the movement, the number of visited corners, the latency, and the number of rearings were recorded. Bizarre behaviors (stretching, skipping, backward and bizarre circling) were identified during the gait and exploratory activity execution. The results corroborate that in the face of novelty and recognition of places, old 3xTg-AD mice exhibit increased bizarre behaviors than mice with normal aging. Bizarre circling and backward movement delayed the elicitation of horizontal and vertical locomotion and exploratory activities. Besides, kyphosis (differentiated into flexible and rigid) stood out as more characteristic of 3xTg-AD mice than C57BL/6 and a limitation in spontaneous gait and vertical activity performances. The study of co-occurrence of psychomotor impairments and anxiety-like behaviors is helpful for understanding and managing the progressive functional deterioration in patients with AD.

  • Open access
  • 60 Reads

Pomegranate juice (PJ) is a rich source of ellagitannins, precursors of colonic metabolite - urolithin A believed to contribute to pomegranate's neuroprotective effect. While many experimental studies involving PJ role in Alzheimer's disease and hypoxic-ischemic brain injury have been carried out, our knowledge of pomegranate's effects against Parkinson's disease (PD) is very limited. Previously we have reported that PJ treatment improved the postural stability, which correlated well with the enhancement of neuronal survival, protection against oxidative damage, and α-synuclein aggregation. Since olfactory and motor deficits are typical symptoms of PD, in this study, we aimed to investigate the capability of PJ for protecting the olfactory, motoric and neurochemical alterations. To evaluate its efficiency, Wistar rats were given the combined treatment with ROT and PJ (500 mg/kg/day p.o) for 35 days. After that, we assessed olfactory discrimination index (DI) and vertical and horizontal activities as well as dopamine level in the dissected midbrain and cortex of animals.

Our findings provide the first evidence that PJ treatment protects against impairment of DA neurotransmission in the midbrain and cortex that correlated well with the enhanced olfactory discrimination performance. In addition, PJ ameliorated motor deficit as evidenced by the maintenance of vertical activity at the control level.

  • Open access
  • 143 Reads

Cranberry juice (CJ) is a rich source of polyphenols with strong antioxidant activity believed to contribute to this fruit's wide range of health benefits. However, to date, our knowledge of cranberry neuroprotective potential is very scarce and limited to only a few in vitro studies. Recently, we have reported that treatment of rats with CJ controls oxidative stress in several organs with the most noticeable effect in the brain. In this study, we examined the capability of cranberry juice for protection against Parkinson's disease (PD) in a rat model of parkinsonism induced by rotenone (ROT). Wistar rats were given the combined treatment with ROT and cranberry juice (CJ) (200 and 500 mg/kg/day p.o) for 35 days. To evaluate its neuroprotective effect, microscopic examination, determination of inflammation and apoptosis markers, and α-synuclein level were performed in the midbrain. Our results indicated that CJ treatment provided neuroprotection as evidenced by the enhancement of neuronal survival, which correlated well with decreased expression of pro-apoptotic proteins including caspase 9, Bax, and cytochrome c as well as declined α-synuclein level. However, the expression of tumor necrosis factor-alpha was similar across all groups with no statistically significant differences.

  • Open access
  • 298 Reads
Diagnosis of Conditions Mimicking Neurological Disease

A vexing problem for clinicians in the emergency department is the presentation of a patent who exhibits the symptoms and signs of neurological disease that merit immediate life-living interventions. Clinicians must consider conditions without apparent pathology that resemble neurological disease requiring urgent care.

Reviewing the literature on neurological disease and conditions displaying symptoms and signs that may resemble neurological disease produced a framework to characterize traits to distinguish neurological disease and mimics.

Results and Discussion:
Neurological disease, an involuntary movement, must be differentiated from conversion disorder [functional neurological symptom disorder (FND)], a condition characterized by symptoms and signs without apparent pathology that may resemble neurological disease. Although FND represents involuntary movements, voluntary pathways generate the symptoms and signs. FND requires an interview and examination to make a positive diagnosis. Treatments include physical, occupational, speech, and cognitive-behavioral therapies.

Neurological disease must also be differentiated from voluntary disorders including emotional expressions such as zaghrouta, ululation expressed at happy events in the Middle East, and fabricated conditions, such as malingering and factitious disorder.

Awareness of specific characteristics of neurological disease and conditions without an apparent pathological basis that may be confused is crucial to the accurate diagnosis and treatment of patients who present with symptoms and signs suggesting neurological disease. Application of appropriate diagnostic assessments will provide the basis for the application of precision medicine tailored to the needs of the individual patient.

  • Open access
  • 79 Reads
Analysis of different expressions of genes in self-organizing nueruloids model in the ectodermal compartment of Huntington disease patient using single-cell RNA-Seq

Mutations in the huntingtin gene (HTT) on chromosome 4 leading to repetition of CAG codon more than 36 times (mHTT) will result in autosomal dominant Huntington’s disease (HD). mHTT protein not only disrupts the gene regulation of mitochondrial function-related proteins, but also affects microtubules, mitochondrial dynamic fusion and division, and calcium transport. In this research, we aimed to investigate the cellular pathways affected by mHTT in in vitro models of HD.

To address this aim, we re-analyzed publicly available single-cell RNA-Seq (scRNA-Seq) dataset from neuroloids derived from patients with and without HD previously published by Haremaki et al. (2019) in Nature. The normalized count matrix provided by authors was re-analyzed using Seurat package in RStudio, the data were integrated, filtered and differentially expressed genes between control cells and cell derived from patients with HD were plotted. The results were compared with other publicly available scRNA-Seq datasets.

The use of scRNA-Seq datasets and in vitro models of HD allows us to compare single cell gene expressions from specific cell types of interest. The gene expression differences between neuroloids derived from HD and control patients may help to identify the effects of mHTT mutation, shedding the light on the cellular pathways affected in HD.

  • Open access
  • 47 Reads
From acute inflammatory demyelinating polyradiculoneuropathy to non-Hodgkin's lymphoma - a challenge for diagnosis and treatment

Introduction: Paraneoplastic neurological syndromes (PNS), such as Guillain-Barre syndrome (GBS) are rarely associated with non-Hodkin's lymphoma (NHL), so far only isolated cases have been reported.

Material and method: This study aimed to assess scientific activity regarding non-Hodgkin's lymphoma and Guillain–Barré syndrome related research. We retrieved publications from Web of Science (WoS) and the VOSviewer tool was used to perform bibliometric analysis and visualization. In order to (1) provide an overview of the research in the field and (2) examine linkages/gaps/frontiers betwen/of researches, network diagrams based on authors, keywords, sources, references, citations were created. Key-concepts and relevant terminology of the topic are also identified. Paraneoplastic sensory-motor neuropathies that precede the diagnosis of lymphomas are mainly demyelinating neuropathies that may meet the diagnostic criteria for Guillain-Barré syndrome. The diagnosis, but especially the treatment of patients with GBS and NHL is a challenge, which requires a good collaboration between neurologists and hematologists as well as the evaluation of specialized studies, in order to choose the optimal therapeutic scheme. Also, using the VOSviewer tool we were allowed to find that more patients develop GBS after instituting chemotherapy for the NHL (17 studies) and in only 7 cases Guillain-Barré syndrome preceded the diagnosis of non-Hodgkin's lymphoma.

Conclusions: Hematological malignancies can be aggravated by neurological disorders, each condition requiring separate treatment. Also, most of the time, the treatment of hematological disease induces the onset of Guillaine-Barre syndrome. This association of diseases, even if it is rare, must be known by specialists to allow a rapid therapeutic intervention. In addition, the use of the VOSvieview tool allowed us to evaluate publications in the Web of Science (WoS), providing easy access to published studies related to this topic, so that the therapeutic scheme of this category of patients can be facilitated.

  • Open access
  • 45 Reads
Intrinsic (genotype) and extrinsic (environment) factors in the temporal patterns of nest-building process:
Effect of forced isolation in old female mice with normal and AD-pathological aging

The impact of isolation has become a critical worldwide issue since the outbreak of the COVID-19 pandemic. In nursing homes, the physical distance measures forced the separation of old patients in restricted areas and rooms to avoid the spread of the virus. Similarly, older people living at home face severe restrictions as the best preventive strategy to protect their lives before vaccination is possible/effective. At the translational level, we recently demonstrated the impact of isolation in male 3xTg-AD mice for Alzheimer's disease and the increase of gross and fine motor activity. The latter was monitored through nesting, a species-typical ethological behavior used as a naturalistic approach to measuring animals' well-being and abilities in instrumental tasks. In the present work, we scored the nests and the nest-building process in old females under the effects of intrinsic (genotype, 3xTg-AD vs. C57BL/6J) and extrinsic (environment, forced isolation vs. social environment) factors. Nests were scored according to the ordinal Deacon Scale, whereas the temporal progress of nests construction was determined with a new parametric (numeric) measurement analog. The results confirmed previously described genotype differences, with worse nests in 3xTg-AD mice living under standard housing conditions than non-transgenic counterparts, at 48 and 72 hours. However, the genotype effect was lost under isolation, mainly due to isolated 3xTg-AD females enhancing nest-building behavior, while isolated non-transgenic counterparts were less efficient at 24h. The results also indicate that temporal patterns of the nest-building process are important to be considered when measuring the effects of intrinsic and extrinsic factors.

  • Open access
  • 92 Reads
High definition tDCS effect on postural control in healthy individuals: entropy analysis of a crossover clinical trial

Objective: The identification of dose-response effects of transcranial direct current stimulation (tDCS) on postural control after stroke has highlighted this strategy as promising for post-stroke rehabilitation. Nonetheless, spatial-temporal dependence data have not been investigated using entropy analysis. Thus, we performed a nonlinear time series analysis of ground reaction force during and after the application of the high-definition transcranial direct current stimulation (HD-tDCS), over the right temporo-parietal junction (TPJ). Materials and Methods: We conducted a randomized, double-blind, placebo-controlled, crossover clinical trial. Twenty-one healthy young adults received the HD-tDCS and sham protocols. We evaluated the exchanging information (causal direction) between both force plates, using the summarized time series of transfer entropy, and compared the dose-response across the healthy subjects by a generalized linear mixed model (GLMM). Results: We found significant variation during the dynamic information flow (p<0.001) among the dominant bodyside. Specifically, all participants were right-handed, and a greater force transfer was observed from the right- to the left-side during the experiment. We observed a causal relationship in the information flow (equilibrium force transfer) from right to left and a decrease in entropy over time. Conclusions: HD-tDCS intervention induced a dynamic influence over time on postural control. Right-TPJ stimulation using HD-tDCS can induce an asymmetry of body weight distribution, leaning to the contralateral side of the stimulation, and thus a plausible post-stroke treatment.

  • Open access
  • 44 Reads
Measuring Temporal Patterns of the Nest-building Process in Mice for Animal Welfare and Disease Monitoring

Nesting behavior in rodents is a species-typical ethological behavior used as a naturalistic instrument for measuring animal welfare/illness and behavioral aspects related to instrumental tasks. It is also proposed as valuable for disease monitoring, evaluating potential risk factors and preventive/therapeutical interventions. The reliability of Deacon’s scale to score nests at 24 h is well-recognized, and it is based on a 5-point ordinal scale ranging from 'not noticeably touched nesting material' to 'perfect nest'. In previous work using an animal model of Alzheimer's disease and wild-type counterparts, we proposed a 3-day protocol to discard false negatives, thus unveiling genotype-, sex- and age-dependent differences. Now, we propose the size of nesting as a numeric variable complementary to the ordinal scale. This would allow the required parametric repeated measures analysis to identify and evaluate temporal patterns in the nest-building process. For this purpose, nests of male and female mice with normal (C57BL/6) and AD-pathological aging were measured using paper nesting material and our 3-days protocol. The results showed that the nest-building process responded to a linear equation in wild-type animals or when female sex was considered. However, the lineal progression was found disrupted in males or the AD-genotype. Genotype per sex interaction indicated that the nest-building process was optimal in wild-type females, as they build the best nests at 72h. On each day, data were consistent with the ordinal scale, but the identification of temporal patterns with the numeric variable confirmed nest-building as a complex process, which is sensitive to sex and genotype.

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