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Minocycline protects against lipopolysaccharide-induced glial cells activation and oxidative stress damage in the medial prefrontal cortex (mPFC) of the rat

Abdo Qaid EY, Abdullah Z, Zakaria R, Long I

Int J Neurosci, 2024 Jun;134(1):56-65.
PMID: 35638219 DOI: 10.1080/00207454.2022.2084092

PURPOSE/AIM: Neuroinflammation and oxidative stress have been encountered in neurodegenerative diseases such as Alzheimer's disease (AD). However, the neuroprotective effects of minocycline against lipopolysaccharide (LPS)-induced glial cells activation and oxidative stress damage in the medial prefrontal cortex (mPFC) of rats are still elusive. The purpose of this study is to investigate the effects of minocycline and memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on the microglia and astrocytes expression, as well as oxidative stress levels in the mPFC of LPS injected rats.
MATERIALS AND METHODS: Fifty adult Male Sprague Dawley rats were divided into five groups: control, LPS (5 mg/kg), LPS treated with minocycline (25 mg/kg), LPS treated with minocycline (50 mg/kg) and LPS treated with memantine (10 mg/kg). The immunohistochemistry and western blotting were used to analyse the expressions and densities of microglia marker (Iba-1) and astrocyte marker, (GFAP) while enzyme-linked immunosorbent assay (ELISA) was used to measure the protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels.
RESULTS: In comparison to the control group, the expression and density of Iba-1 and GFAP were significantly enhanced in the LPS group (p

Matched MeSH terms: Prefrontal Cortex/metabolism
Fulltext Identification of pathways for bipolar disorder: a meta-analysis

Nurnberger JI, Koller DL, Jung J, Edenberg HJ, Foroud T, Guella I, et al.

JAMA Psychiatry, 2014 Jun;71(6):657-64.
PMID: 24718920 DOI: 10.1001/jamapsychiatry.2014.176

IMPORTANCE: Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders.
OBJECTIVE: To identify biological pathways that contribute to risk for bipolar disorder (BP) using genes with consistent evidence for association in multiple genome-wide association studies (GWAS).
DATA SOURCES: Four independent data sets with individual genome-wide data available in July 2011 along with all data sets contributed to the Psychiatric Genomics Consortium Bipolar Group by May 2012. A prior meta-analysis was used as a source for brain gene expression data.
STUDY SELECTION: The 4 published GWAS were included in the initial sample. All independent BP data sets providing genome-wide data in the Psychiatric Genomics Consortium were included as a replication sample.
DATA EXTRACTION AND SYNTHESIS: We identified 966 genes that contained 2 or more variants associated with BP at P cortex.
MAIN OUTCOMES AND MEASURES: Empirically significant genes and biological pathways. RESULTS Among 966 genes, 226 were empirically significant (P cortex in patients with BP: CACNA1C, DTNA, FOXP1, GNG2, ITPR2, LSAMP, NPAS3, NCOA2, and NTRK3.
CONCLUSIONS AND RELEVANCE: Pathways involved in the genetic predisposition to BP include hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicate neuronal development pathways as well. These results tend to reinforce specific hypotheses regarding BP neurobiology and may provide clues for new approaches to treatment and prevention.

Matched MeSH terms: Prefrontal Cortex/metabolism
Fulltext Minocycline Attenuates Lipopolysaccharide-Induced Locomotor Deficit and Anxiety-like Behavior and Related Expression of the BDNF/CREB Protein in the Rat Medial Prefrontal Cortex (mPFC)

Abdo Qaid EY, Abdullah Z, Zakaria R, Long I

Int J Mol Sci, 2022 Nov 03;23(21).
PMID: 36362262 DOI: 10.3390/ijms232113474

Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits and anxiety-like behaviour. In this study, minocycline was compared to memantine, an NMDA receptor antagonist, for its effects on LPS-induced locomotor deficits and anxiety-like behaviour in rats. Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to an LPS (5 mg/kg, i.p.) injection. Locomotor activity and anxiety-like behaviour were assessed using the open-field test (OFT). The phosphorylated tau protein level was measured using ELISA, while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and Western blot, respectively. Minocycline treatment reduced locomotor deficits and anxiety-like behaviour associated with reduced phosphorylated tau protein levels, but it upregulated BDNF/CREB protein expressions in the mPFC in a comparable manner to memantine, with a higher dose of minocycline having better benefits. Minocycline treatment attenuated LPS-induced locomotor deficits and anxiety-like behaviour in rats and decreased phosphorylated tau protein levels, but it increased the expressions of the BDNF/CREB proteins in the mPFC.

Matched MeSH terms: Prefrontal Cortex/metabolism
Fulltext A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Shen X, Howard DM, Adams MJ, Hill WD, Clarke TK, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, et al.

Nat Commun, 2020 05 08;11(1):2301.
PMID: 32385265 DOI: 10.1038/s41467-020-16022-0

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR

Matched MeSH terms: Prefrontal Cortex/metabolism*
Fulltext Age-related changes in the metabolic profiles of rat hippocampus, medial prefrontal cortex and striatum

Durani LW, Hamezah HS, Ibrahim NF, Yanagisawa D, Makpol S, Damanhuri HA, et al.

Biochem Biophys Res Commun, 2017 11 25;493(3):1356-1363.
PMID: 28970069 DOI: 10.1016/j.bbrc.2017.09.164

We have recently shown that age-dependent regional brain atrophy and lateral ventricle expansion may be linked with impaired cognitive and locomotor functions. However, metabolic profile transformation in different brain regions during aging is unknown. This study examined metabolic changes in the hippocampus, medial prefrontal cortex (mPFC) and striatum of middle- and late-aged Sprague-Dawley rats using ultrahigh performance liquid chromatography coupled with high-resolution accurate mass-orbitrap tandem mass spectrometry. Thirty-eight potential metabolites were altered in hippocampus, 29 in mPFC, and 14 in striatum. These alterations indicated that regional metabolic mechanisms in lated-aged rats are related to multiple pathways including glutathione, sphingolipid, tyrosine, and purine metabolism. Thus, our findings might be useful for understanding the complexity of metabolic mechanisms in aging and provide insight for aging and health span.

Matched MeSH terms: Prefrontal Cortex/metabolism*
Fulltext Validating a functional near-infrared spectroscopy diagnostic paradigm for Major Depressive Disorder

Husain SF, Yu R, Tang TB, Tam WW, Tran B, Quek TT, et al.

Sci Rep, 2020 06 16;10(1):9740.
PMID: 32546704 DOI: 10.1038/s41598-020-66784-2

Reduced haemodynamic response in the frontotemporal cortices of patients with major depressive disorder (MDD) has been demonstrated using functional near-infrared spectroscopy (fNIRS). Most notably, changes in cortical oxy-haemoglobin during a Japanese phonetic fluency task can differentiate psychiatric patients from healthy controls (HC). However, this paradigm has not been validated in the English language. Therefore, the present work aimed to distinguish patients with MDD from HCs, using haemodynamic response measured during an English letter fluency task. One hundred and five HCs and 105 patients with MDD took part in this study. NIRS signals during the verbal fluency task (VFT) was acquired using a 52-channel system, and changes in oxy-haemoglobin in the frontal and temporal regions were quantified. Depression severity, psychosocial functioning, pharmacotherapy and psychiatric history were noted. Patients with MDD had smaller changes in oxy-haemoglobin in the frontal and temporal cortices than HCs. In both regions of interest, oxy-haemoglobin was not associated with any of the clinical variables studied. 75.2% and 76.5% of patients with MDD were correctly classified using frontal and temporal region oxy-haemoglobin, respectively. Haemodynamic response measured by fNIRS during an English letter fluency task is a promising biomarker for MDD.

Matched MeSH terms: Prefrontal Cortex/metabolism
Fulltext Modulation of Proteome Profile in AβPP/PS1 Mice Hippocampus, Medial Prefrontal Cortex, and Striatum by Palm Oil Derived Tocotrienol-Rich Fraction

Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Makpol S, et al.

J Alzheimers Dis, 2019;72(1):229-246.
PMID: 31594216 DOI: 10.3233/JAD-181171

Tocotrienol-rich fraction (TRF) is a mixture of vitamin E analogs derived from palm oil. We previously demonstrated that supplementation with TRF improved cognitive function and modulated amyloid pathology in AβPP/PS1 mice brains. The current study was designed to examine proteomic profiles underlying the therapeutic effect of TRF in the brain. Proteomic analyses were performed on samples of hippocampus, medial prefrontal cortex (mPFC), and striatum using liquid chromatography coupled to Q Exactive HF Orbitrap mass spectrometry. From these analyses, we profiled a total of 5,847 proteins of which 155 proteins were differentially expressed between AβPP/PS1 and wild-type mice. TRF supplementation of these mice altered the expression of 255 proteins in the hippocampus, mPFC, and striatum. TRF also negatively modulated the expression of amyloid beta A4 protein and receptor-type tyrosine-protein phosphatase alpha protein in the hippocampus. The expression of proteins in metabolic pathways, oxidative phosphorylation, and those involved in Alzheimer's disease were altered in the brains of AβPP/PS1 mice that received TRF supplementation.

Matched MeSH terms: Prefrontal Cortex/metabolism*
Electrical Stimulation Normalizes c-Fos Expression in the Deep Cerebellar Nuclei of Depressive-like Rats: Implication of Antidepressant Activity

Huguet G, Kadar E, Temel Y, Lim LW

Cerebellum, 2017 04;16(2):398-410.
PMID: 27435250 DOI: 10.1007/s12311-016-0812-y

The electrical stimulation of specific brain targets has been shown to induce striking antidepressant effects. Despite that recent data have indicated that cerebellum is involved in emotional regulation, the mechanisms by which stimulation improved mood-related behaviors in the cerebellum remained largely obscure. Here, we investigated the stimulation effects of the ventromedial prefrontal cortex (vmPFC), nucleus accumbens (NAc), and lateral habenular nucleus on the c-Fos neuronal activity in various deep cerebellar and vestibular nuclei using the unpredictable chronic mild stress (CMS) animal model of depression. Our results showed that stressed animals had increased number of c-Fos cells in the cerebellar dentate and fastigial nuclei, as well as in the spinal vestibular nucleus. To examine the stimulation effects, we found that vmPFC stimulation significantly decreased the c-Fos activity within the cerebellar fastigial nucleus as compared to the CMS sham. Similarly, there was also a reduction of c-Fos expression in the magnocellular part of the medial vestibular nucleus in vmPFC- and NAc core-stimulated animals when compared to the CMS sham. Correlational analyses showed that the anxiety measure of home-cage emergence escape latency was positively correlated with the c-Fos neuronal activity of the cerebellar fastigial and magnocellular and parvicellular parts of the interposed nuclei in CMS vmPFC-stimulated animals. Interestingly, there was a strong correlation among activation in these cerebellar nuclei, indicating that the antidepressant-like behaviors were possibly mediated by the vmPFC stimulation-induced remodeling within the forebrain-cerebellar neurocircuitry.

Matched MeSH terms: Prefrontal Cortex/metabolism