The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art.

Parkinson's disease (PD) is a neurodegenerative disorder affecting 2-3% of those aged over 65, characterized by motor symptoms like slow movement, tremors, and muscle rigidity, along with non-motor symptoms such as anxiety and dementia. Lewy bodies, clumps of misfolded proteins, contribute to neuron loss in PD. Mutations in the GBA1 gene are considered the primary genetic risk factor of PD. GBA1 mutations result in decreased activity of the lysosomal enzyme glucocerebrosidase (GCase) resulting in α-synuclein accumulation. We know that α-synuclein aggregation, lysosomal dysfunction, and endoplasmic reticulum disturbance are recognized factors to PD susceptibility; however, the molecular mechanisms connecting GBA1 gene mutations to increased PD risk remain partly unknown. Thus, in this narrative review conducted according to a systematic review method, we aimed to present the main contributions arising from the molecular impact of the GBA1 gene to the pathogenesis of PD providing new insights into potential impacts for advances in the clinical care of people with PD, a neurological disorder that has contributed to the substantial increase in the global burden of disease accentuated by the aging population. In summary, this narrative review highlights the multifaceted impact of GBA1 mutations in PD, exploring their role in clinical manifestations, genetic predispositions, and molecular mechanisms. The review emphasizes the importance of GBA1 mutations in both motor and non-motor symptoms of PD, suggesting broader therapeutic and management strategies. It also discusses the potential of CRISPR/Cas9 technology in advancing PD treatment and the need for future research to integrate these diverse aspects for improved diagnostics and therapies.

The role of gut-brain axis in a rotenone-induced rat model of Parkinson's disease.

Parkinson's disease (PD) is a widespread neurodegenerative condition affecting millions globally. This investigation centered on the gut-brain axis in a rotenone-induced PD rat model. Researchers monitored behavioral shifts, histological modifications, neurodegeneration, and inflammation markers throughout the rats' bodies. Results revealed that rotenone-treated rats displayed reduced exploration (p = 0.004) and motor coordination (p < 0.001), accompanied by decreased Nissl staining and increased alpha-synuclein immunoreactivity in the striatum (p = 0.009). Additionally, these rats exhibited weight loss (T3, mean = 291.9 ± 23.67; T19, mean = 317.5 ± 17.53; p < 0.05) and substantial intestinal histological alterations, such as shortened villi, crypt architecture loss, and inflammation. In various regions, researchers noted elevated immunoreactivity to ionized binding adapter molecule (IBA)-1 (p < 0.05) and reduced immunoreactivity to glial fibrillary acidic protein (p < 0.05) and S100B (p < 0.001), indicating altered glial cell activity. Overall, these findings imply that PD is influenced by gut-brain axis changes and may originate in the intestine, impacting bidirectional gut-brain communication.

The impact of child poverty on brain development: does money matter?

The development of the human nervous system makes up a series of fundamental and interdependent events involving birth, growth, and neuronal maturation, in addition to the positive or negative selection of synapses of these neurons that will participate in the composition of neural circuits essential to the activity of the nervous system. In this context, where environment and social relationships seem to be relevant markers for neurodevelopment, advanced neuroimaging techniques and behavioral assessment tools have demonstrated alterations in brain regions and cognitive functions among children developing in low or high socioeconomic status environments. Considering the aspects mentioned, this review aimed to identify the importance of socioeconomic status in children's brain development, seeking to identify what are the impacts of these factors on the morphological and physiological formation of the nervous system, allowing a greater understanding of the importance of environmental factors in neurodevelopmental processes.

O desenvolvimento do sistema nervoso humano compõe uma série de eventos fundamentais e interdependentes envolvendo o nascimento, crescimento e maturação neuronal, além da seleção positiva ou negativa de sinapses desses neurônios que participarão da composição de circuitos neurais essenciais à atividade do sistema nervoso. Nesse contexto, em que o ambiente e as relações sociais parecem ser marcadores relevantes para o neurodesenvolvimento, técnicas avançadas de neuroimagem e ferramentas de avaliação comportamental têm demonstrado alterações em regiões cerebrais e funções cognitivas em crianças que se desenvolvem em ambientes de baixo ou alto nível socioeconômico. Considerando os aspectos mencionados, esta revisão teve como objetivo identificar a importância do status socioeconômico no desenvolvimento cerebral infantil, buscando identificar quais são os impactos desses fatores na formação morfológica e fisiológica do sistema nervoso, permitindo maior compreensão da importância dos fatores ambientais nos processos de neurodesenvolvimento.

Reversible cerebral vasoconstriction syndrome: literature review.

Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a neurovascular condition characterized by a severe sudden-onset headache that may be associated with focal neurological deficits. On imaging, the suggestive finding corresponds to multifocal vasoconstriction of the cerebral arteries, with a spontaneous resolution of approximately 12 weeks. The identification of precipitating factors and diagnosis must be carried out early, so that adequate management is established and the patient has a good prognosis, given the risk of secondary complications and residual neurological deficits. This study consists of a literature review based on the analysis of articles published between 2017 and 2022 in PubMed, SciELO, and ScienceDirect on RCVS, intending to understand the clinical and radiological characteristics, diagnosis, treatment, and prognosis of patients with RCVS. The pathophysiology, drug management, and prognosis still lack solid evidence; therefore, further studies on RCVS are needed to expand medical knowledge and avoid underdiagnosis and inadequate treatment of this important condition.

Premotor, nonmotor and motor symptoms of Parkinson's Disease: A new clinical state of the art.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.

Resistance exercise improves learning and memory and modulates hippocampal metabolomic profile in aged rats.

Physical activity has been considered an important non-medication intervention to preserve mnemonic processes during aging. However, how resistance exercise promotes such benefits remains unclear. A possible hypothesis is that brain-metabolic changes of regions responsible for memory consolidation is affected by muscular training. Therefore, we analyzed the memory, axiety and the metabolomic of aged male Wistar rats (19-20 months old in the 1st day of experiment) submitted to a 12-week resistance exercise protocol (EX, n = 11) or which remained without physical exercise (CTL, n = 13). Barnes maze, elevated plus maze and inhibitory avoidance tests were used to assess the animals' behaviour. The metabolomic profile was identified by nuclear magnetic resonance spectrometry. EX group had better performance in the tests of learning and spatial memory in Barnes maze, and an increase of short and long-term aversive memories formation in inhibitory avoidance. In addition, the exercised animals showed a greater amount of metabolites, such as 4-aminobutyrate, acetate, butyrate, choline, fumarate, glycerol, glycine, histidine, hypoxanthine, isoleucine, leucine, lysine, niacinamide, phenylalanine, succinate, tyrosine, valine and a reduction of ascorbate and aspartate compared to the control animals. These data indicate that the improvement in learning and memory of aged rats submitted to resistance exercise program is associated by changes in the hippocampal metabolomic profile.

The role of microglia in prion diseases and possible therapeutic targets: a literature review.

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that leads to progressive neurodegeneration due to gliosis, vacuolation of central nervous system tissue, and loss of neurons. Microglia play a crucial role in maintaining Central Nervous System (CNS) homoeostasis, both in health and disease, through phagocytosis and cytokine production. In the context of CJD, the immunomodulatory function of microglia turns it into a cell of particular interest. Microglia would be activated by infectious prion proteins, initially acquiring a phagocytic and anti-inflammatory profile (M2), and producing cytokines such as IL-4, IL-10, and TGF-ß. Therefore, microglia are seen as a key target for the development of new treatment approaches, with many emerging strategies to guide it towards a beneficial role upon neuroinflammation, by manipulating its metabolic pathways. In such a setting, many cellular targets in microglia that can be involved in phenotype modulation, such as membrane receptors, have been identified and pointed out as possible targets for further experiments and therapeutic approaches. In this article, we review the major findings about the role of microglia in CJD, including its relationship to some risk factors associated with the development of the disease. Furthermore, considering its central role in neural immunity, we explore microglial connection with other elements of the immune system and cell signalling, such as inflammasomes, the complement and purinergic systems, and the latest finding strategies to guide these cells from harmful to beneficial roles.

Vertical one-and-a-half syndrome in a patient with pecheron artery ischemia: A case report.

Vertical one-and-a-half syndrome (VOHS) is an uncommon presentation resulting from a unilateral thalamomesencephalic stroke with involvement of the rostral interstitial nucleus of the medial longitudinal fasciculus and posterior commissure. The artery of Percheron (aPe) is a branch of the posterior cerebral artery (PCA) and it is a variant that arises as a solitary trunk supplying both medial thalami and upper midbrain. A 78-year-old female patient, presented at the hospital emergency with approximately 12 hours of sudden onset of diplopia, associated with dizziness. Neurological exam revealed torsional nystagmus associated with bilateral upgaze palsy with limitation of infraduction on the left. We describe a rare case of VOHS associated with ischemic alterations at the MRI suggesting an aPe impairment. The conjugate gaze control lies anatomically at the midbrain at the central nervous system (CNS). This report describes a rare type of VOHS and brings a new insight on a possible aPe topography possibly causing this clinical presentation.

Dementia and cognitive impairment in adults as sequels of HSV-1-related encephalitis: a review.

Considering the variety of mechanisms of Herpes simplex virus (HSV-1) contamination and its broad invasive potential of the nervous system, a life-long latent infection is established. Infected adult individuals may be susceptible to viral reactivation when under the influence of multiple stressors, especially regarding immunocompromised patients. This guides a series of neuroinflammatory events on the cerebral cortex, culminating, rarely, in encephalitis and cytotoxic / vasogenic brain edema. A sum of studies of such processes provides an explanation, even though not yet completely clarified, on how the clinical evolution to cognitive impairment and dementia might be enabled. In addition, it is of extreme importance to recognize the current dementia and cognitive deficit worldwide panorama. The aim of this literature review is to elucidate the available data upon the pathophysiology of HSV-1 infection as well as to describe the clinical panorama of the referred afflictions.

Considerando a variedade de mecanismos de contaminação pelo vírus Herpes simplex (HSV-1) e seu amplo potencial invasivo do sistema nervoso, uma infecção latente por toda a vida é estabelecida. Indivíduos adultos infectados podem ser suscetíveis à reativação viral quando estão sob a influência de múltiplos estressores, principalmente em pacientes imunocomprometidos. Esse fator orienta uma série de eventos neuroinflamatórios no córtex cerebral, culminando, raramente, em encefalite e edema cerebral citotóxico/vasogênico. Um somatório de estudos desses processos fornece uma explanação, embora ainda não totalmente esclarecida, de como a evolução clínica para déficit cognitivo e demência pode ser possibilitada. Além disso, é de extrema importância reconhecer o panorama mundial atual da demência e do déficit cognitivo. O objetivo da presente revisão de literatura é elucidar os dados disponíveis sobre a fisiopatologia da infecção pelo HSV-1, assim como descrever o panorama clínico das referidas afecções.

Effects of Chronic Photobiomodulation with Transcranial Near-Infrared Laser on Brain Metabolomics of Young and Aged Rats.

Since laser photobiomodulation has been found to enhance brain energy metabolism and cognition, we conducted the first metabolomics study to systematically analyze the metabolites modified by brain photobiomodulation. Aging is often accompanied by cognitive decline and susceptibility to neurodegeneration, including deficits in brain energy metabolism and increased susceptibility of nerve cells to oxidative stress. Changes in oxidative stress and energetic homeostasis increase neuronal vulnerability, as observed in diseases related to brain aging. We evaluated and compared the cortical and hippocampal metabolic pathways of young (4 months old) and aged (20 months old) control rats with those of rats exposed to transcranial near-infrared laser over 58 consecutive days. Statistical analyses of the brain metabolomics data indicated that chronic transcranial photobiomodulation (1) significantly enhances the metabolic pathways of young rats, particularly for excitatory neurotransmission and oxidative metabolism, and (2) restores the altered metabolic pathways of aged rats towards levels found in younger rats, mainly in the cerebral cortex. These novel metabolomics findings may help complement other laser-induced neurocognitive, neuroprotective, anti-inflammatory, and antioxidant effects described in the literature.