Current Neuropharmacology - Online First

Genetic variations in the microtubule-associated protein tau (MAPT) gene play a central role in Alzheimer's disease (AD) pathogenesis. Two major MAPT haplotypes, H1 and H2, show differential associations with tau expression and AD risk. However, data from Middle Eastern populations remain limited, restricting our understanding of population-specific disease susceptibility patterns and therapeutic responses.

We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. Search terms included “MAPT haplotype,” “Alzheimer's disease,” “H1 H2,” “tau pathology,” and “pharmacogenetics.” We analyzed peer-reviewed articles published between 2000 and 2024, focusing on studies reporting haplotype frequencies, MAPT expression levels, APOE interactions, and clinical outcomes. This review synthesizes published data without generating new experimental results.

The H1 haplotype consistently associates with increased MAPT expression, tau accumulation, and elevated AD risk, particularly in APOE ε4 noncarriers. Conversely, the H2 haplotype appears protective, correlating with reduced tau burden and slower cognitive decline. Notably, recent reports reveal significant overrepresentation of the H2 haplotype in the Jordanian population compared to European and East Asian cohorts, where H2 frequency is substantially lower or absent. This distinct genetic architecture suggests altered regional AD risk profiles.

The elevated H2 frequency in Jordan represents a unique population-specific genetic signature that may influence regional AD susceptibility patterns. These findings challenge current risk models predominantly based on European populations and suggest the need for population-tailored approaches in neurodegenerative disease research. The naturally H2-enriched Jordanian cohort provides an exceptional opportunity to investigate protective mechanisms against tau pathology.

MAPT haplotype distributions show significant population variation with important implications for AD risk assessment and therapeutic targeting. The high H2 frequency in Jordan warrants integration into personalized medicine frameworks and population-specific disease models, potentially informing more effective regional prevention and treatment strategies.

Frontotemporal dementia (FTD) is the third most frequent dementia and the leading dementia subtype in individuals under 65. The discovery of C9orf72 (chromosome 9 open reading frame 72) GGGGCC abnormal expansion is a major genetic cause of both FTD and amyotrophic lateral sclerosis (ALS), linking these diseases along a clinicopathological spectrum. This study aimed to depict the research landscape of C9orf72 in FTD over the past decade, track emerging research hotspots, and provide insights into under-researched areas.

Based on the Web of Science database, a bibliometric analysis was conducted to explore publication trends, key contributors, funding sources, journal categories, co-authorship networks, and keyword co-occurrence, clustering, and bursts.

A total of 1,220 articles were identified, with sustained output of over 100 articles annually. The majority of contributions and funding support came from North America and Europe. Hot research themes included hexanucleotide repeats, nucleocytoplasmic transport, disease mechanisms, and therapeutic targets.

North America and Europe were highly productive, supported by higher regional prevalence, genetic burden, and robust funding. Ploy-GR in cerebrospinal fluid has emerged as a diagnostic biomarker. Pathogenic mechanisms remain complex, involving both gain- and loss-of-function effects. Metformin and antisense oligonucleotides were considered as potential therapeutics. Further research is needed in underrepresented populations and on the translational potential of emerging molecular targets.

This study offers a comprehensive overview of current trends and future directions over the past decade in C9orf72-related FTD research, allowing researchers—particularly those new to the area—to quickly understand the current landscape.

Dysfunction of the pathway between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) may be responsible for the weaker or lack of efficacy of antidepressant drugs in patients suffering from treatment-resistant depression. This study aims to evaluate the behavioural effects of vHPC lesion with ibotenic acid (IBO) in animals subjected to the chronic mild stress (CMS) procedure and treated with either chronic venlafaxine or acute deep brain stimulation (DBS) in the mPFC. In addition, electrophysiological studies are expected to reveal neuromodulatory effects on the function and plasticity of mPFC neurons in response to stress, lesion, and deep brain stimulation (DBS).

Wistar Han rats were exposed to the chronic mild stress model of depression and IBO lesion in vHPC. The effects of both procedures were evaluated in a series of behavioural tests (sucrose test, elevated plus maze, novel object recognition, and social interaction) and in electrophysiological recordings (field potential recording and LTP induction).

The CMS procedure caused a decrease in sucrose consumption, deficits in cognitive function and social interaction, and increased anxiety. The lesion in vHPC with IBO resulted in similar behavioral changes. Repeated (5 weeks) administration of venlafaxine (10 mg/kg, IP) reversed these deficits in stressed animals but was only partially effective in reversing the effects of IBO lesion in HPC. In contrast, the neuromodulation strategy with DBS of the mPFC produced a robust reversal of all behavioural changes observed in both stressed and lesioned rats. The CMS did not affect the amplitude of field potentials in mPFC slices, but the induction of Long-Term Potentiation was impaired in these animals. The IBO lesion significantly reduced the amplitude of Field potentials as compared to unstressed rats. Both repeated venlafaxine and acute DBS normalized these effects of the IBO lesion.

Observed effects were fully normalized by DBS in mPFC but not by venlafaxine, which only partially reversed the IBO lesion-induced effects. The weaker sensitivity of vHPC-lesioned animals to the therapeutic action of venlafaxine provides further evidence that insufficient transmission from the vHPC to the mPFC could be responsible for antidepressant non-response.

These data support the hypothesis that resistance to antidepressant treatment may result from the inability of antidepressants to fully activate the impaired vHPC-PFC pathway, which could be overcome by the neuromodulatory properties of deep brain stimulation.

The COVID-19 pandemic triggered unprecedented changes in the scholarly publishing landscape, particularly in biomedical fields such as Neurosciences and Neuropharmacology. Several journals experienced steep, short-term increases in citation metrics during 2020-2022. However, it remains uncertain whether these surges reflected a sustainable impact or temporary inflation. This study aimed to analyze post-pandemic bibliometric behavior by evaluating the Rate of Change (RoC) in key journal-level indicators from 2013 to 2023.

A retrospective longitudinal study was conducted on 233 neuroscience journals indexed in the Journal Citation Reports. Six indicators were analyzed: Journal Impact Factor (JIF), Eigenfactor Score, Immediacy Index, Article Influence Score, Cited Half-Life, and Total Citations. RoC was calculated for each metric on an annual basis. Mixed-effects models with random intercepts and slopes were constructed to evaluate longitudinal trajectories and identify changes associated with three defined periods: pre-pandemic (2013-2019), pandemic (2020-2022), and post-pandemic (2023). Subgroup analyses assessed journal quartiles and categories to explore variations in impact resilience.

The pandemic period (2020-2022) showed significant increases in RoC for JIF (mean β = +4.85, p = 0.004), Immediacy Index (β = +6.22, p = 0.002), and Total Citations (β = +5.88, p < 0.001). These changes were more prominent in top-quartile journals and those classified under Neuropharmacology. In contrast, alternative metrics such as the Eigenfactor Score and Article Influence Score remained relatively stable across the same period. In 2023, most indicators exhibited a normalization trend, with JIF and Immediacy Index showing marked deceleration in RoC, suggesting a post-pandemic recalibration. Journals with sustained positive trajectories were primarily concentrated in high-impact clusters, with Current Neuropharmacology ranking among the top performers by RoC slope.

The findings demonstrate that the surge in citations during the pandemic was primarily transitory and varied across bibliometric indicators. Traditional metrics like JIF and Immediacy Index were more sensitive to systemic shocks, while influence-based indicators (Eigenfactor and Article Influence Score) showed higher temporal resilience. The application of RoC allowed for a nuanced interpretation of metric trajectories and minimized misinterpretation of short-term spikes. Limitations include reliance on publicly available data and potential lag effects in citation behavior not fully captured within the 10-year window.

This study reveals that pandemic-era citation inflation in Neuroscience journals was largely temporary and metric-dependent. RoC-based modeling offers a reproducible and adaptable approach for assessing the sustainability of bibliometric trends. These insights can help editors, funders, and academic institutions better understand journal performance, make informed decisions about research dissemination, and refine metrics-based evaluation frameworks in the post-pandemic publishing environment.

Cerebral ischemia (CI) is a severe neurological disorder characterized by high incidence and disability rates. Its pathogenesis is complex, involving multiple interrelated biological processes. Among these, intercellular communication has emerged as a key mechanism regulating the damage and recovery phases of CI. It controls information exchange between cells, thereby playing a crucial role in cellular responses to ischemic injury. Understanding how intercellular communication promotes the pathophysiology of CI may provide valuable insights into new therapeutic targets.

To elucidate the role of intercellular communication in CI, recent literature was analyzed, with a focus on how intercellular communication influences cellular behaviors and metabolism. This review integrates data from molecular biology, cellular signaling studies, and cerebral ischemia models.

Studies indicate that intercellular communication significantly influences the progression and outcomes of CI. Intercellular communication not only participates in regulating the inflammatory response following injury but also plays a dual role in neuroprotection and regeneration.

The dual role of intercellular communication—exacerbating damage through inflammatory cascades and promoting recovery through neuroprotective mechanisms—highlights its complex contribution to the pathology of CI. Cellular crosstalk between neurons, glial cells, endothelial cells, and immune cells coordinates the dynamic response to ischemic injury. Understanding these dynamics offers promising opportunities for targeted interventions.

Intercellular communication plays a central role in the mechanisms of injury and repair in cerebral ischemia. By influencing inflammation, neuroprotection, and regeneration, it serves as both a mediator of injury and a potential therapeutic target. Further research is needed to fully elucidate these mechanisms and translate them into effective clinical strategies for treating CI.