Aluminium metal (Al) has been implicated in the etiology of many neurodegenerative diseases, most commonly the Alzheimer's disease (AD). Al causes biochemical defects by affecting the neurotransmitters level, causes conformational changes in amyloid β protein and increases amyloid accumulation in brain. This study was aimed at evaluating neuroprotective effect of Ibuprofen (IBU) (25 mg/kg/day for 12 days) in AlCl3-induced (150 mg/kg/day for 12 days) toxicity. Treated mice were subjected to learning and memory tests. Cholinergic muscarinic receptors (mAChR; M1-M5) and APP isoforms (APP695, APP770 and APP common) gene expression were carried out from the pre-frontal cortex area. Profound effect on learning and memory was observed in IBU treated group along with enhanced expression of M1 mAChR (0.40 ± 0.03; p < 0.01) compared to AlCl3-induced toxicity group (0.05 ± 0.02). Fear memory was improved in IBU treated group (89.68 ± 2.58, p < 0.01) as compared to AlCl3-induced toxicity group (54.58 ± 8.21). Discrimination index in social novelty test in IBU treated group was improved (81.13 ± 8.71; p < 0.05), compared to AlCl3-induced toxicity group (46.28 ± 5.55). Similarly, recognition memory of IBU treated group in novel object recognition test (NOB) was retained (66.85 ± 5.60; p < 0.05) as compared to AlCl3-induced toxicity group (33.06 ± 11.80). IBU demonstrated memory enhancing effect, however, its effect on the APP isoforms expression in pre-frontal cortex needs further studies.

Dopamine β-hydroxylase (DBH) is a copper-containing enzyme that has an important role in maintaining the cellular homeostasis between the two neurotransmitters, dopamine (DA) and nor-adrenaline (NA...

Background: Monoamine oxidase A (MAOA) has a role in metabolising different biogenic amines, including dopamine. Functional studies have revealed the effect of promoter region variants on the transcriptional activity of the MAOA that consequently affects the homeostasis of the biogenic amines which might implicate in the aetiology of multiple psychiatric conditions. Objectives: The current study aimed to determine the influence of the promoter region 30 base pair (bp), a variable number of tandem repeats (VNTR) of the MAOA, on its serum levels and association with schizophrenia (SHZ), bipolar disorder (BD), and major depressive disorder (MDD) in the Pakistani population. Methods: A total of 1062 subjects [MDD n = 416, BD n = 200, SHZ n = 97 and controls n = 349], were genotyped for MAOA-30bp µVNTR through standard polymerase chain reaction technique and logistic regression was applied to determine the genetic association. Serum MAOA levels were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann-Whitney U test was applied. Results: In genotype analysis, eight different repeat (R) alleles of MAOA-30 bp µVNTR were observed, where 4.5R, 5.5R, and 6R were the rare repeats found in the current Pakistani cohort. In serum-based analysis the total MAOA serum levels were found to be significantly elevated in SHZ; however, in sub-group analysis, significantly higher serum levels of MAOA were observed only in the rare allele groups of MDD, BD, and SHZ. Conclusions: The current study gives us further insights into the complex nature of MAOA regulation and its genetic and serum-levels association with different psychiatric conditions.