Journal of Neural Transmission最新文献

Alcohol use disorder (AUD) is a relapsing brain disorder involving major neurobiological changes. Upon alcohol exposure, dopamine (DA) levels increase in the nucleus accumbens (nAc), a key region of the mesolimbic DA system involved in reward and reinforcement. A concomitant increase in extracellular taurine within the nAc has been shown to be important for the alcohol-induced DA increase. Sex differences in alcohol consumption and in the development of AUD have previously been shown. However, knowledge regarding sex differences in alcohol-induced DA and concomitant taurine release is limited. The aim of this study was to examine potential sex differences in alcohol-induced increases of extracellular levels of DA and taurine within the nAc, following local and systemic alcohol administration. To this end, in vivo microdialysis was performed using male and female Wistar rats. Following systemic alcohol administration, both male and female rats displayed a significant increase of both DA and taurine within the nAc, with no observed sex differences. In contrast, males displayed a significant increase in both DA and taurine following alcohol administration locally into the nAc whilst female rats displayed a blunted DA response and an attenuated taurine increase. Basal levels of DA or taurine did not differ significantly between males and females. The results presented here suggest that local accumbal mechanisms contribute to a greater extent to the alcohol-induced DA increase in male compared to female rats, whilst the response to systemic alcohol administration is similar between sexes.

Non-pharmacological interventions are increasingly recognized as first-line therapies for managing dementia symptoms alongside pharmacologic strategies. Among these, therapy gardens and horticultural interventions have emerged as promising adjunctive approaches. This pilot study aimed to evaluate the effects of a six-month dementia-friendly therapy garden intervention on psychological well-being, specifically depression levels, and to determine whether baseline dementia severity predicts treatment success. The study was conducted in a real-world setting, with a final sample of 28 dementia patients. Unlike previous studies, this intervention incorporated multimodal stimulation, including sensory, motor, and cognitive elements. Results indicated a significant reduction in depression, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) after six months of intervention (p <.05). However, depression scores assessed using the Hamilton Depression Rating Scale (HAM-D) showed only a trend toward improvement but did not reach statistical significance. No improvements were observed at the three-month mark, suggesting that sustained engagement is necessary for measurable benefits. Cognitive function, as assessed by dementia severity, did not show significant improvement, and dementia severity at baseline was not a significant predictor of treatment response. These findings underscore the potential of dementia-friendly therapy gardens to provide meaningful psychological benefits by significantly reducing depression over time. Notably, even individuals with more advanced dementia benefited, challenging the prevailing notion that non-pharmacological interventions are primarily effective in early disease stages. These results highlight the need for further research on the long-term effects and mechanisms underlying garden-based interventions in dementia care.

Auditory processing abnormalities are a prominent feature of Autism Spectrum Disorder (ASD), significantly affecting sensory integration, communication, and social interaction. This review delves into the neurobiological mechanisms underlying these deficits, including structural and functional disruptions in the auditory cortex, imbalances in excitatory and inhibitory signaling, and synaptic dysfunction. Genetic contributions from mutations in CNTNAP2, SHANK3, FMR1, and FOXP2 are explored, highlighting their roles in auditory abnormalities. Animal models, such as BTBR^T+tf/J mice (BTBR) and valproic acid (VPA)-exposed rodents, provide critical insights into the sensory abnormalities observed in ASD. In addition, the review discusses current pharmacological strategies and emerging interventions targeting neurotransmitter systems and synaptic plasticity. Notably, future directions are emphasized, highlighting the need for integrated pharmacological and auditory-specific therapies to enhance sensory processing and communication outcomes in ASD. Overall, this review aims to bridge the gap between basic neurobiological research and clinical application, guiding future studies and therapeutic developments in ASD-related auditory processing deficits.

While diagnostic criteria have been established and validated for most neurodegenerative diseases, the considerable overlap between individual nosological entities remains a significant diagnostic challenge. Increasing evidence suggests that neurodegeneration is often initiated by inflammation within the central nervous system. The identification of inflammation could serve as a first signal of the pathophysiological process. As such, validated biological markers ("biomarkers") of neuroinflammation are critically important. This study aimed to assess the presence and levels of inflammatory biomarkers in three neurodegenerative diseases: Lewy body diseases (LBD), multiple system atrophy (MSA), and 4-repeat tauopathies (4RT). A total of 83 LBD, 24 MSA, and 31 4RT patients were included, with 83 control subjects for comparison. Six immune-related proteins were analysed in cerebrospinal fluid (CSF) and blood serum (serum): C3 complement, C4 complement, haptoglobin, transferrin, orosomucoid, and β2 microglobulin (β2M). ANCOVA statistical analysis revealed significantly lower levels of several inflammatory biomarkers in LBD (CSF: transferrin, C3 complement, orosomucoid; Serum: orosomucoid, β2M) and MSA (CSF: transferrin, C3 complement, C4 complement, orosomucoid) compared to controls. Significant differences were also observed between the synucleinopathy patient groups (LBD and MSA) and 4RT in serum levels of C3 complement. Additionally, the CSF/serum quotients for transferrin (LBD and MSA) and C3 complement (LBD) were significantly lower in disease relative to controls. These findings suggest that inflammatory processes may play a role in the pathophysiology of neurodegenerative proteinopathies, warranting further research to confirm these associations. The identification of potential fluid biomarkers would then represent a promising step forward in the field.

The clinical characteristics of dystonia occurring in association with sporadic neurodegenerative parkinsonism have not been systematically explored or compared with those of idiopathic adult-onset dystonia. This study aims to compare demographic and clinical features, including the distribution of dystonia at onset, dystonia-associated features, and the propensity for spread between patients with combined dystonia-parkinsonism and those with idiopathic adult-onset dystonia. Patients were selected from the Italian Dystonia Registry. The study cohort included 130 patients with combined dystonia-parkinsonism and 355 age- and sex-matched patients with isolated adult-onset idiopathic dystonia. The comparison between combined dystonia-parkinsonism and idiopathic dystonia revealed differences in the distribution of dystonia across body regions, with non-task-specific upper limb dystonia, lower limb dystonia, and trunk dystonia occurring more frequently in patients with combined dystonia-parkinsonism. Additionally, this group exhibited a lower frequency of head tremor, eye symptoms associated with blepharospasm, and sensory tricks, alongside a comparable frequency of neck pain related to cervical dystonia and a family history of dystonia or tremor. The clinical presentation of dystonia differs between combined dystonia-parkinsonism and idiopathic dystonia, especially in terms of the body regions affected. These differences underscore the necessity for additional research and suggest underlying pathophysiological disparities between etiological categories that could significantly influence future diagnostics and therapeutic approaches.

Speech impairment is a common and disabling symptom of Parkinson's disease (PD). We aimed to reveal the motor, nonmotor, and other clinical factors that might be associated with voice disturbances in PD. Remarkably, we aimed to present a possible specific clinical phenotype more prone to display speech disturbances. We included all the patients with PD who visited our movement disorders clinic between March 2023 and March 2024 and whose information regarding the clinical features and scale results was fully available. In addition to detailed demographic data, comprehensive clinical assessments were performed. We included 232 PD patients with a mean age of 64.4 ± 10.5 y (F/M = 145/87). The median disease duration was 4 y. The comparative analyses of the patients with and without voice handicaps (VH) revealed that patients with VH had higher disease duration and LED. They got higher scores in all the clinical scales, including MDS-UPDRS 1, 2, 3, 4, FOGQ, FES-I, HAM-A, and HDRS revealing a more severe disease stage However, multiple linear regression models revealed only the MDS-UPDRS 4 score, HAM-A score, and MDS-UPDRS-3 (on) score [- 10,658 + 2297*MDS-UPDRS-4 + 0949*HAI + 0549*MDS-UPDRS-3 (on)] as predictors of VHI. Our results support increasing speech problems with higher motor stage, and motor complication score. Besides, we also draw attention to anxiety, which is associated with speech problems in the general community, but only in an experimental study of PD pathology.

Treatment with levodopa, a precursor of dopamine (DA), to compensate for the loss of endogenous DA in Parkinson's disease (PD), has been a success story for over 50 years. However, in late stages of PD, the progressive degeneration of dopaminergic neurons and the ongoing reduction in endogenous DA concentrations make it increasingly difficult to maintain normal-like DA function. Typically, in late PD, higher doses of levodopa are required, and the fluctuations in striatal DA concentrations-reflecting the timing pattern of levodopa administrations-become more pronounced. These DA fluctuations can include highs that induce involuntary movements (levodopa-induced dyskinesia, LID) or lows that result in insufficient suppression of PD symptoms ("OFF" phases). The enhanced fluctuations primarily arise from the loss of DA buffering capacity, resulting from the degeneration of DA neurons, and an increased reliance on levodopa-derived DA release as a "false neurotransmitter" by serotonergic neurons. In many patients, the LID and OFF-phases can be alleviated by modifying the levodopa therapy to provide a more continuous delivery or by using additional medications, such as monoamine oxidase-B (MAO-B) inhibitors, amantadine, or dopaminergic receptor agonists. Understanding the challenges faced by levodopa therapy also requires considering that the PD striatum is characterized not only by the loss of DA neurons but also by neuroplastic adaptations and PD-induced degenerations of other neural populations. This review provides a broad overview on the use of levodopa in treating PD, with a focus on the underlying science of the challenges encountered in late stages of the disease.

Neurovascular coupling ensures that cerebral blood flow (CBF) is proportionally matched to neural activity. In patients with chronic cerebral hypoperfusion, this may be clinically assessed through multiple regression analysis with cognitive function and the cerebrovascular reserve (CVR) as key factors. Cognitive function (based on neuropsychological testing using the Neurobehavioral Cognitive Status Examination [COGNISTAT]) and cerebrovascular risk factors, including CBF, CVR (as evaluated using N-isopropyl-p-¹²³I-iodoamphetamine single-photon emission computed tomography with acetazolamide challenge), and periventricular hyperintensity (PVH) grade, were investigated in 65 patients with steno-occlusive disease of a main cerebral artery. Multiple regression analysis was performed between COGNISTAT scores and other factors in 41 patients with a vascular mild cognitive impairment pattern on COGNISTAT and a proportionally variable CVR range. Additionally, we examined subgroups based on HbA1c, PVH grade, and lipid values, as well as 10 patients who underwent anastomosis surgery. The multiple regression analysis of COGNISTAT scores and CVR showed statistically significant relationships in the 41 patients and all subgroups (adjusted R² > 0.45). The high HbA1c and high PVH grade groups exhibited lower standardized partial regression coefficients (SPRCs) for CVR compared with the lower groups (0.187, 0.203 vs. 0.230, 0.254, respectively). After anastomosis surgery, both COGNISTAT scores and CVR significantly improved while their relationship was maintained (SPRC = 0.224, p = 0.0092, adjusted R² = 0.457). A significant regression relationship was found between cognitive function and CVR, indicating a potential causal relationship based on clinical neurovascular coupling function that may vary depending on HbA1c level and PVH grade.

This paper presents a novel framework for understanding the interaction between cognitive and emotional processes, recognizing the complex and dynamic relationship between these two constructs. The framework categorizes cognitive functions into four distinct categories: Cold Cognition, Hot Cognition, Warm Cognition, and Cool Cognition. By distinguishing between the style of processing (intuitive vs. analytical) and the content of information (emotional vs. non-emotional), the framework provides a model for both assessment and intervention. For assessment, it helps categorize cognitive and emotional processes, enabling targeted evaluations based on specific processing styles and content. For interventions, it supports the development of training programs that address processing styles in relation to the target function, improving the effectiveness of therapeutic and developmental strategies. Overall, this framework has the potential to advance both theoretical understanding and practical applications in cognitive and emotional assessment and training.