Studies comparing mercury (Hg) levels with those of age-matched controls often focus on identifying exposure risks in patients with Alzheimer’s disease (AD), including the release of mercury from long-term dental amalgams. Mercury exposure can lead to oxidative stress and inflammation, along with Abeta and hyperphosphorylated tau accumulation in the brain. Mercury accumulation has been demonstrated in AD transgenic mice, and certain chemokines have been shown to contribute to cognitive impairment. However, the link between mercury, cognitive dysfunction and chemokines remains to be elucidated in AD patients with long-term dental amalgams.

Our study aims to determine whether peripheral CCL2 chemokine and mercury levels differ between AD patients with long-term dental amalgams compared to patients without AD.

Mercury levels were quantified by ICP-MS (in hair: µg/g), peripheral CCL2 chemokine ligand levels were measured by ELISA, and cognitive impairment was evaluated by a Mini Mental Test. We compared the CCL2 biomarker and mercury levels in patients with long-term dental amalgams without AD (n = 42), AD patients without dental amalgams (n = 55), AD patients with long-term dental amalgams (n = 13 AD + dental amalgams), and age-matched controls without dental amalgams (n = 42 without AD).

Our results indicate a 17% rise in mercury levels in patients with AD and dental amalgams compared to AD patients without dental amalgams, while a rise in MCP-1 levels was observed using the Mann–Whitney test (p = 0.048). Within the AD+dental amalgam group, 16% showed cognitive impairment according to their Mini Mental scores. These peripheral MCP-1 increases correlated with mercury levels in AD patients with long-term dental amalgams. MCP-1 levels correlated with Mini Mental scores using the Spearman correlation test (r = 0.45, p < 0.05, AD + dental amalgam group). Additionally, mercury levels correlated with MMSE scores. However, these correlations were absent in the other study groups.

Conclusion: AD patients with long-term dental amalgams have higher peripheral MCP-1 levels and lower Mini Mental scores.

Background: Kaolin, an aluminum silicate usually injected intracisternally, induces hydrocephalus by causing an inflammatory reaction and fibrous scarring in the meninges; this leads to an obstruction of the cerebrospinal fluid (CSF) pathways, and ventricular enlargement ensues. Its effect on the histomorphometry of the hippocampus is yet to be fully explored; therefore this study aimed at assessing the histomorphology and histomorphometry changes in the hippocampus of hydrocephalic adult rats induced with sterile kaolin. Methods: Comminicating Hydrocephalus was induced intracisternally in adult rats, both sexes, using 0.04ml of 250mg/ml of kaolin (n=6), while the sham procedure was performed on controls (n=6), where a needle was introduced into their cisternal magna to mimic kaolin-induced hydrocephalus but no injection was performed. Rats were weighed weekly and then sacrificed on the fourth week via intracardiac perfusion to harvest the brain tissues. Harvested brains were processed for Cresyl violet-staining to assess neuronal damage. Data were analysed using GraphPad Prism 8 and ImageJ software. Results: In the quantitative analysis, the body weights of the rats induced with kaolin were significantly lower than those of the control rats (p<0.0001), while in the qualitative analysis, photomicrographs of Cresyl violet-stained hippocampal regions, CA1, CA3 and the Dentate Gyrus, showed a severely disorganized laminal cytoarchitecture of hydrocephalic rats compared to the control, and the pyknotic indices (PIs) of CA1, CA3 and the Dentate Gyrus of the 250mg/ml group were significantly higher than those of the control. Conclusion: Findings from this study showed that hydrocephalus altered the cytoarchitecture of the pyramidal neurons of the hippocampus of adult rats following intracisternal kaolin injection.

Introduction: Homocysteine (Hcy), homocysteine thiolactone (HTL), N-Hcy-proteins and dysfunction of bleomycin hydrolase (BLMH) are associated with Alzheimer's disease (AD). AD is characterized by the accumulation of amyloid-β (Aβ) plaques. Aβ is formed from amyloid-β precursor protein (APP) via the amyloidogenic pathway, involving β-secretase BACE1 and γ-secretase complex (Nicastrin, PSEN1, PEN2, APH-1). The impact of Hcy, its metabolites and BLMH dysfunction on the development and progression of AD is not fully understood.

Objective: We tested the hypothesis that Hcy, its metabolites and Blmh silencing affect APP processing pathways in mouse neuroblastoma N2a-APPswe cells.

Methods: Neuroblastoma N2a-APPswe cells harboring a human transgene with a mutation in the APP gene were treated with different concentrations of Hcy, HTL or N-Hcy-proteins. The expression of the Blmh gene was silenced using a Blmh-specific siRNA. Scrambled siRNA was used as a negative control. Proteins involved in APP metabolism pathway, i.e., APP, phospho-APP, BACE1, PSEN1, PEN2 and Nicastrin, were quantified by Western blotting. The expression of APP, Bace1 Psen1, Psenen and Ncstn mRNAs was analyzed by RT-qPCR.

Results: Hcy increased APP, phospho-APP, BACE1 and PSEN1. At mRNA level, Hcy downregulated the expression of the Psen1 gene. HTL increased protein levels of APP, BACE1, PSEN1 and Nicastrin. This treatment also decreased the expression of the Psenen gene (encoding PEN2). Treatments with N-Hcy-proteins increased level of PSEN1 protein and downregulated the expression of the Psenen gene. There was no significant impact of treatments on PEN2 protein level. Silencing of the Blmh gene resulted in upregulation of APP, Nicastrin, PEN2 and downregulation of BACE1 protein. Silencing significantly upregulated the expression of APP and Psenen mRNAs.

Conclusions: Hcy, HTL, N-Hcy-protein and Blmh gene silencing resulted in dysregulated APP processing in N2a-APPswe cells, suggesting their association with AD progression.

Acknowledgement: Supported by NCN grant 2021/43/B/NZ4/00339.

The ancestral Mapuche people of southern Chile have a rich ethnobotanical tradition based on knowledge of the use of medicinal plants for health care and spiritual balance. Currently, oxidative stress is recognized as one of the mechanisms involved in the pathophysiology of neurodegenerative diseases such as Alzheimer's and Parkinson's, which is why research in the field of medicinal chemistry has focused on finding natural compounds from species with high neuroprotective potential. This paper presents a systematic review with an ethnopharmacological focus on native Chilean plants used by the Mapuche community to treat symptoms compatible with neurodegenerative processes. Based on semi-structured interviews and a review of scientific databases, the species Aristotelia chilensis, Buddleja globosa, Fuchsia magellanica, Drymis winteri, Peumus boldus, and Ugni molinae were highlighted. These species have been evaluated through the metabolomic characterization of polar and aqueous extracts with high concentrations of polyphenolic compounds and have demonstrated strong antioxidant effects and inhibition of the intracellular production of reactive oxygen species (ROS). Likewise, Adiantum capillus-veneris, Baccharis tola, Berberis darwinii, Crytocarpa alba, Gevuina avellana, Greigia sphacelata, Lapageria rosea, Laurelia sempervirens, Lophosoria quadripinnata, Otholobium glandulosum, and Weinmannia trichosperma are also reported to have neuroprotective potential. Infusions and decoctions are the main forms of preparation in communities, which is directly related to the study methodologies for their chemical validation. This study contributes to the assessment and relevance of the Chilean Pharmacopoeia and the importance of preserving traditional knowledge. Ethnobotany is a source of inspiration and biomedical research in the search for therapeutic alternatives for diseases related to neuronal damage.

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder frequently accompanied by gastrointestinal dysfunction. Chronic Helicobacter pylori infection has been proposed as a modifiable factor influencing motor severity and levodopa pharmacokinetics. This systematic review aimed to evaluate whether H. pylori infection is associated with worse motor outcomes or impaired levodopa response in patients with Parkinson’s disease.

Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and regional databases were searched for studies published between 2010 and 2025 in English or Spanish. Eligible publications included human observational studies, interventional studies assessing H. pylori eradication, and systematic reviews or meta-analyses reporting motor severity (UPDRS-III), motor fluctuations, or levodopa response. A qualitative narrative synthesis was performed due to clinical and methodological heterogeneity across studies.

Results: Eighteen studies met our inclusion criteria, including 11 observational studies, 4 interventional eradication studies, and 3 systematic reviews/meta-analyses. Observational studies consistently reported that H. pylori-positive PD patients exhibited higher motor severity scores, increased motor fluctuations, delayed levodopa onset, and reduced daily “on” time compared with non-infected patients. Interventional studies demonstrated that successful H. pylori eradication was associated with improvements in motor fluctuations and, in some cases, reductions in UPDRS-III scores. Systematic reviews and meta-analyses supported a detrimental association between H. pylori infection and motor outcomes, although heterogeneity and moderate risk of bias were noted across included studies.

Conclusions: Available evidence suggests that Helicobacter pylori infection is associated with worse motor severity and impaired levodopa response in Parkinson’s disease. While eradication therapy appears to improve motor fluctuations, variability in study design and risk of bias limit definitive conclusions. Future well-designed randomized controlled trials and quantitative syntheses are warranted to clarify causality and inform clinical recommendations.

Tau being a difficult target: intrinsically disordered, conformationally plastic, heavily post-translationally modified, and capable of adopting multiple fibrillar states in disease. Genetic variation within MAPT (e.g., coding SNPs at regulatory phosphorylation sites such as S262, S356) and splicing-related haplotypes modulates tau’s biochemistry and disease risk. Tau hyperphosphorylation, misfolding and aggregation drive axonal transport failure, synaptic loss, and neuronal death across tauopathies. Traditional ligand-screens using a single tau construct miss the broader landscape of proteoforms and patient-specific variants. Phytochemicals or Polyphenols (e.g., curcumin, EGCG, resveratrol), alkaloids (berberine, huperzine A), and terpenoids (ginkgolides) emerged as dominant scaffolds. Quantitative mapping revealed these compounds consistently attenuate tau phosphorylation at key epitopes (S262, S356, S396/S404), inhibit fibrillization, and restore microtubule stability through multitarget actions on GSK3β, CDK5, and PP2A pathways. In this systematic review and scientometric analysis, we identified and profiled 186 studies investigating phytochemicals with tau-modulating activity. Mining of MAPT variant data highlighted regulatory SNPs near phosphorylation sites S262 and S356 that modulate tau’s phosphorylation kinetics and aggregation propensity. Network pharmacology linked tau and its regulatory enzymes to central hubs including VEGFA, IL1B, ESR1, and APP, suggesting that efficacious phytochemicals confer combined tau-directed and anti-inflammatory or neurotrophic effects. AlphaFold-based structural modeling of wild-type and variant tau isoforms enabled molecular docking of 42 prioritized compounds. Top-ranked hits curcumin analogs, EGCG, and asiaticoside exhibited strong binding near the microtubule-binding domain with favorable CNS permeability and low predicted toxicity based on ADMET profiling. Together, these analyses delineate phytochemical scaffolds that combine direct biochemical modulation of pathogenic tau states with network-level neuroprotective activity. The integrated genetic–structural–systems framework presented here provides a rational basis for advancing multitarget phytochemicals as stratified therapeutics in tauopathies.

Introduction
Parkinson’s disease (PD) presents heterogeneous motor deficits associated with disruptions in distinct neural circuits. White-matter plasticity can be examined using diffusion tensor imaging (DTI) and fractional anisotropy (FA). Rhythmic Auditory Stimulation (RAS) induces compensatory plasticity within the basal ganglia-thalamo-cortical (BGTC) and cerebello-thalamo-cortical (CTC) networks, which are differentially preserved in rigidity-dominant (RD) and tremor-dominant (TD) PD, respectively. However, tract-specific plasticity underlying these effects remains poorly understood. This study examined FA differences in the internal capsule (IC), cerebellar projections, and corpus callosum (CC) to characterize subtype-specific neuroplasticity relevant to Neurologic Music Therapy (NMT).

Methods
Seventeen PD patients were classified as TD (n=11) or RD (n=6) using UPDRS scores. DTI data were processed in FSL and analyzed using tract-based spatial statistics. FA differences were assessed in predefined white-matter tracts. Principal component analysis (PCA) examined cerebellar peduncle (CP) organization.

Results
RD patients showed significantly higher FA in the left IC and across all CC subregions compared to TD patients. No group differences were observed in cerebellar projections. PCA revealed a unilateral left superior CP contribution in RD, whereas TD patients showed distributed bilateral contributions across all CPs.

Discussion
Findings suggest localized motor tract alterations and stronger interhemispheric connectivity in RD, contrasted with preserved, distributed cerebellar organization in TD. These subtype-specific patterns have implications for tailoring NMT interventions, with RD potentially benefiting from bilateral and cognitive–motor strategies and TD from cerebellar-based motor sequencing approaches.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are crucial for brain health and neuroplasticity. n-3 PUFA deficiency is associated with deficits in mood regulation and memory. This study evaluated the effects of chronic n-3 PUFA supplementation on the prefrontal cortex (PFC) and hippocampus (HIPP) in female rats exposed to a lifelong n-3 PUFA–deficient diet.

Female Wistar rats were exposed to either an n-3 PUFA–poor diet (rich in omega-6) or an n-3 PUFA–enriched diet (rich in α-linolenic acid) from conception until 8 weeks. After 9 weeks, n-3 PUFA supplementation was introduced until 16 weeks. At 16 weeks, neurochemical analyses were conducted in the PFC and HIPP, measuring neurotransmitters (5-HT, DA, NA), neurotrophic factors (BDNF, NGF), synaptic markers (SYN, CAMKII), and amyloid-related markers (amyloid oligomers, APP) using HPLC and Western blotting.

Our results showed that n-3 PUFA supplementation reversed most neurochemical alterations induced by the n-3 PUFA–poor diet in both the PFC and HIPP. Reduced levels of 5-HT and DA in both brain regions under the n-3 PUFA–poor diet were restored to control values following supplementation, while increased NA levels were normalized. SYN expression was reduced in both regions under the n-3 PUFA–poor diet and was restored after supplementation. CAMKII expression was also restored in the PFC, whereas no significant changes were observed in the HIPP. BDNF levels were reduced in both the PFC and HIPP under the n-3 PUFA–poor diet and were fully restored following supplementation. NGF levels were similarly restored in the HIPP, and no significant changes were detected in PFC. Amyloid-related markers showed limited recovery and remained elevated compared to control levels.

We concluded that n-3 PUFA supplementation restores neurotransmitter balance, synaptic function, and neurotrophic support, suggesting its therapeutic potential in neurodegenerative disorders. However, the partial reversal of amyloid-related markers indicates that early-life nutritional deficiency may lead to persistent neurodegenerative vulnerability.

Introduction: Monosodium glutamate (MSG), a widely used flavor enhancer, is associated with neurotoxicity and oxidative stress in the brain. Hibiscus sabdariffa aqueous extract (HSAE), rich in polyphenols and anthocyanins, is known for its antioxidant properties and may mitigate MSG-induced brain damage. Nothing has been done previouisly on effect of HSAE on MSG-induced toxicity hence, the reason for this study which is also a part of a depression study.

Objectives: This study aimed to evaluate the antioxidant and neuroprotective effects of HSAE on MSG-induced alterations in mice brains, focusing on oxidative stress markers, antioxidant enzyme levels, acetylcholinesterase activity, and histological changes in the hippocampal dentate gyrus.

Methodology: Male Swiss mice of ages between 8 to 10 weeks were used and divided into six groups (n=6): control, MSG (2.5 g/kg), fluoxetine (Flx as standard from previous literature reviews, 20 mg/kg), and HSAE (50, 100, and 200 mg/kg) co-treated with MSG.

The extract, standard and MSG were prepared freshly and administered daily for 14 days. MSG was administered via subcutaneous route while the extract and standard was administered via intraperitoneal route. 30 minutes after administration, behavioural tests were carried out then sacrificed to extract brain samples used for the antioxidant assays. Samples were extracted, homogenised and supernatants were decanted and kept for further use. The supernatant was assayed for malondialdehyde (MDA), nitrite, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase activities (AchE) activities using spectrophotometric methods. Histological analysis of the dentate gyrus was performed to assess neuronal damage.

Results: MSG significantly increased MDA, nitrites, and acetylcholinesterase levels while reducing GSH, CAT, and SOD levels, indicating oxidative stress and cholinergic disruption. HSAE (100 and 200 mg/kg) and Fluoxetine significantly reversed MDA, nitrites, and acetylcholinesterase elevations. HSAE (200 mg/kg) and Fluoxetine significantly restored GSH. CAT and SOD levels were also improved, with HSAE (200 mg/kg) showing CAT levels comparable to Fluoxetine. Histological analysis revealed MSG-induced degeneration in the dentate gyrus, with HSAE (200 mg/kg) and Fluoxetine showing significant restoration of neuronal architecture.

Conclusion: HSAE, particularly at 200 mg/kg, exhibits potent antioxidant and neuroprotective effects against MSG-induced neurotoxicity by reducing oxidative stress, enhancing antioxidant defenses, and preserving neuronal structure, comparable to fluoxetine. These findings suggest HSAE’s potential as a therapeutic agent for oxidative stress-related neurodegenerative conditions.

This study is part of a depression study that is ongoing as well.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterised by endoplasmic reticulum (ER) stress, unfolded protein response (UPR) and apoptosis. Elevated plasma total homocysteine (tHcy), known as Hyperhomocysteinemia (HHcy), has been linked to an increased risk of AD. HHcy and related metabolites such as Hcy thiolactone (HTL), N-homocysteinylated (N-Hcy)-protein and bleomycin hydrolase (BLMH), an enzyme that detoxifies HTL, are also associated with AD pathology. However, it is not fully understood how Blmh gene deficiency, Hcy and its metabolites promote ER stress, UPR dysregulation and apoptosis in the development of AD.

Aim: The aim of this research was to study the effects of Hcy, HTL, and N-Hcy-protein treatments and Blmh gene silencing on the expression of genes involved in ER stress, UPR and the apoptosis pathway in mouse N2a-APPswe cells.

Method: N2a-APPswe mouse neuroblastoma cells, which contain a human APP transgene with Swedish mutations, were cultured in complete DMEM/F12 medium. Cells were treated with different concentrations of Hcy, HTL, and N-Hcy-protein in methionine-free medium for 24 h. Blmh gene expression was silenced using Blmh-specific siRNA with Lipofectamine in Opti-MEM medium for 48 h. Proteins involved in ER stress, UPR, and apoptosis were quantified by Western blotting, and the corresponding mRNAs were analysed by RT-qPCR.

Results: Blmh gene silencing, Hcy, HTL, and N-Hcy-protein increased levels of ER chaperone GRP78, indicating the induction of ER stress, which further activated the UPR pathway by increased levels of ATF3 and CHOP. The proapoptotic proteins BAX and CASPASE 3 were increased, whereas the anti-apoptotic protein BCL-2 was reduced, suggesting a shift towards cell death. RT-qPCR analysis confirmed that mRNA expression changes were similar to the protein-level changes.

Conclusion: Blmh gene silencing, Hcy, HTL and N-Hcy-protein may contribute to the development and progression of AD by inducing ER stress, dysregulation of the UPR pathway and apoptosis.