Background: Alzheimer's disease (AD) is a widespread neurodegenerative disorder with a significant global impact, affecting approximately 50 million individuals, and projections estimate that up to 152 million people will be affected by 2050. AD is characterized by beta-amyloid plaques and tau tangles in the brain, leading to cognitive decline.
Summary: Recent research on AD has made significant strides, including the development of an "amyloid clock" biomarker that tracks AD progression through positron emission tomography (PET) scans. Surf4 and other genes have been discovered to play a role in regulating beta-amyloid toxicity, while inhibiting the enzyme hexokinase-2 has shown positive results in preclinical studies. New brain mapping techniques have identified early brain-based causes of cognitive changes in AD, and biomarkers such as neuronal pentraxin protein Nptx2 and astrocytic 7-subunit of the nicotinic acetylcholine receptors (7nAChRs) show potential for early detection. Other approaches, such as replenishing the enzyme Tip60, selectively degrading the modified protein p-p38 with PRZ-18002, and targeting the protein voltage-dependent anion channel-1 (VDAC1), have shown promise in enhancing cognitive function and preventing pathophysiological alterations linked to AD. Baseline blood samples and other biomarkers such as urine formic acid, p-tau 198, microRNAs, and glial fibrillary acidic protein (GFAP) have also been discovered for early detection and intervention of AD. Additionally, recent FDA approvals for medications such as aducanumab and lecanemab provide options for reducing AD symptoms and improving function, while clinical trials for dementia vaccines show promise for the nasal and beta-amyloid 40 vaccines as well as vaccinations targeting tau.
Key messages: These advancements in AD research, including biomarker discovery and the development of disease-modifying treatments, are crucial steps towards improving the lives of those affected by AD and finding a cure for this debilitating disease.
Background: Ischemic stroke is one of the prevalent neurodegenerative disorders; it is generally characterized by sudden abruption of blood flow due to thromboembolism and vascular abnormalities, eventually impairing the supply of oxygen and nutrients to the brain for its metabolic needs. Oxygen-glucose deprived conditions provoke the release of excessive glutamate, which causes excitotoxicity.
Summary: Recent studies suggest that circulatory angiotensin-II (Ang-II) has an imperative role in initiating detrimental events through binding central angiotensin 1 (AT1) receptors. Insufficient energy metabolites and essential ions often lead to oxidative stress during ischemic reperfusion, which leads to the release of proinflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and cytokines like interleukin-18 (IL-18) and interleukin- 1beta (IL-1β). The transmembrane glutamate transporters, excitatory amino acid transporter-2 (EAAT-2), which express in astroglial cells, have a crucial role in the clearance of glutamate from its releasing site and convert glutamate into glutamine in normal circumstances of brain physiology.
Key message: During cerebral ischemia, an impairment or dysfunction of EAAT-2 attributes the risk of delayed neuronal cell death. Earlier studies evidencing that angiotensin receptor blockers (ARB) attenuate neuroinflammation by inhibiting the Ang-II/AT1 receptor-mediated inflammatory pathway and that ceftriaxone ameliorates the excitotoxicity-induced neuronal deterioration by enhancing the transcription and expression of EAAT-2 via the nuclear transcriptional factor kappa-B (NF-kB) signaling pathway. The present review will briefly discuss the mechanisms involved in Ang-II/AT1-mediated neuroinflammation, ceftriaxone-induced EAAT-2 expression, and the repurposing hypothesis of the novel combination of ARBs and ceftriaxone for the treatment of cerebral ischemia.
Background: Schizophrenia is a life-shortening disease. The standardized mortality ratio has been higher than that of the general population, and it has doubled what it was 3-4 decades ago. This rise is mostly attributed to the increased cardiovascular risk associated with high second-generation antipsychotic (SGA) use. Evidence from the first-generation antipsychotic (FGA) era shows a lower prevalence of hypertension (HTN) but data regarding SGAs is scarce.
Purpose: The purpose of the study was to assess the prevalence of HTN and related factors using standardized methodology in patients with schizophrenia on treatment with SGAs.
Methods: A cross-sectional study through convenient sampling was done. Blood pressure, anthropometry, physical activity, and health-related lifestyle factors were assessed using the standard World Health Organization (WHO) methodology of cardiovascular survey methods and the Global Physical Activity Questionnaire (GPAQ) version 2. The prevalence of HTN, obesity, inadequate physical activity, and other demographic and clinical correlates like antipsychotic use, duration of illness, and family history of non-communicable diseases (NCDs) were studied.
Results: The prevalence of HTN is 20.50%, and it increases with age. SGAs with the use of a single agent are the most common. In total, 45.50% of persons with schizophrenia have a positive family history of a NCD; 22.00% and 07.50% are current tobacco and alcohol users, respectively; and 70% have abdominal obesity, and 54% have generalized obesity. Waist circumference, obesity, and family history of NCDs are significant correlates of HTN. A family history of NCDs is the most significant predictor.
Conclusion: The prevalence of HTN is lower than that of the general population despite the high prevalence of SGA use, obesity, and inadequate physical activity.
Background: Internet is an integral part of the daily life of everyone. Internet addiction (IA) is one of the major concerns, specifically among young adults. The association between IA, depression, anxiety, and psychological well-being (PWB) is least studied in young adults.
Purpose: To evaluate IA and its association with psychological morbidity and PWB in a larger sample size. In addition, to examine the factors that are associated with IA.
Methods: A total of 1287 young students were evaluated in the present study. Participants were evaluated on the Internet Addiction Test (IAT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Psychological Well-Being Index-22.
Results: The mean age of the study's participants is 19.5 years. The majority were female (68.9%), from nuclear families (61.8%), and belonged to urban localities (61.5%). On IAT, 15.9% had a presence of IA with a cut-off score of 50. 27.4% and 20.5% had a presence of depression and anxiety with a cut-off score of 10 on the PHQ-9 and GAD-7, respectively. Approximately two-thirds (66.7%) reported poor PWB. IA had a significant positive association with depression and anxiety and a negative association with PWB. Male students, the presence of depression, anxiety, and poor PWB were independent factors associated with IA.
Conclusion: Internet addiction is highly prevalent among college students and has a significant association with anxiety, depression, and poor PWB. There is a need to develop a structured plan, educational strategy, and program to minimize IA in young adults.
Background: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain and is a non-proteinogenic amino acid. Doxorubcin (DOX) or adriamycin is one of the most potent chemotherapy drugs for breast cancer.
Purpose: This study focused on diminishing the brain injury and neurotoxicity of doxorubicin (DOX) by GABA administration.
Methods: Rats were randomly divided into four groups (8 rats each), which were the control group, DOX group (3 mg/kg for 4 weeks, then 2 mg/kg for 2 weeks), GABA group (2 mg/kg for 21 days), and DOX + GABA group (treated as the second and third groups). Neurotoxicity and brain injury were assessed by determining CSF biomarkers, serum inflammatory markers, and histopathological evaluation of the cerebral cortex.
Results: DOX treatment significantly increased the levels of all CSF biomarkers (S100B, IL-1β, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), spectrin breakdown products (SBDP145), and C-C motif chemokine ligand 2 (CCL2) and all inflammatory markers (IL-6, TNF-α, and IFN-γ), causing extensive neutrophilic infiltration and great alteration in the cerebral cortex architecture as evidence of neurotoxicity. The oral administration of GABA significantly reduced the levels of all CSF biomarkers and inflammatory markers and restored the normal architecture of the cerebral cortex, with observed ameliorations in neutrophilic infiltration.
Conclusion: GABA administration can ameliorate neurotoxicity and protect the brain against the negative effects of DOX treatment.
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